NobleBlocks

Beijing Hospital

Hospital / health systemBeijing, China

Research output, citation impact, and the most-cited recent papers from Beijing Hospital (China). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
9.1K
Citations
352.8K
h-index
196
i10-index
7.1K
Also known as
Beijing Hospital

Top-cited papers from Beijing Hospital

Pan-cancer analysis of whole genomes
Lauri A. Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani +4 more
2020· Nature3.3Kdoi:10.1038/s41586-020-1969-6

Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 ; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 ; analyses timings and patterns of tumour evolution 7 ; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 ; and evaluates a range of more-specialized features of cancer genomes 8,10–18 .

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19
Ling Li, Wei Zhang, Yu Hu, Xunliang Tong +4 more
2020· JAMA1.3Kdoi:10.1001/jama.2020.10044

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

Patterns of somatic structural variation in human cancer genomes
Yilong Li, Nicola D. Roberts, Jeremiah A. Wala, Ofer Shapira +4 more
2020· Nature986doi:10.1038/s41586-019-1913-9

Abstract A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes 1–7 . Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types 8 . Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT . A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.

Standards of medical care for type 2 diabetes in China 2019
Weiping Jia, Jianping Weng, Dalong Zhu, Linong Ji +4 more
2019· Diabetes/Metabolism Research and Reviews761doi:10.1002/dmrr.3158

The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes research in China. From 2003 to 2014, four versions of Chinese diabetes care guidelines have been published. The guidelines have played an important role in standardizing clinical practice and improving the status quo of diabetes prevention and control in China. Since September 2016, the CDS has invited experts in cardiovascular diseases, psychiatric diseases, nutrition, and traditional Chinese medicine to work with endocrinologists from the CDS to review the new clinical research evidence related to diabetes over the previous 4 years. Over a year of careful revision, this has resulted in the present, new version of guidelines for prevention and care of type 2 diabetes in China. The main contents include epidemiology of type 2 diabetes in China; diagnosis and classification of diabetes; primary, secondary, and tertiary diabetes prevention; diabetes education and management support; blood glucose monitoring; integrated control targets for type 2 diabetes and treatments for hyperglycaemia; medical nutrition therapy; exercise therapy for type 2 diabetes; smoking cessation; pharmacologic therapy for hyperglycaemia; metabolic surgery for type 2 diabetes; prevention and treatment of cardiovascular and cerebrovascular diseases in patients with type 2 diabetes; hypoglycaemia; chronic diabetic complications; special types of diabetes; metabolic syndrome; and diabetes and traditional Chinese medicine.

Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension
Weili Zhang, ‪Shuyuan Zhang, Yue Deng, Shouling Wu +4 more
2021· New England Journal of Medicine739doi:10.1056/nejmoa2111437

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

Elevated Intakes of Supplemental Chromium Improve Glucose and Insulin Variables in Individuals With Type 2 Diabetes
Richard A. Anderson, Nanzheng Cheng, Noella A. Bryden, Marilyn M. Polansky +3 more
1997· Diabetes584doi:10.2337/diab.46.11.1786

Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. The chromium requirement is postulated to increase with increased glucose intolerance and diabetes. The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes. Individuals being treated for type 2 diabetes (180 men and women) were divided randomly into three groups and supplemented with: 1) placebo, 2) 1.92 micromol (100 microg) Cr as chromium picolinate two times per day, or 3) 9.6 micromol (500 microg) Cr two times per day. Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol (1,000 microg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 +/- 0.2%; 3.85 micromol Cr, 7.5 +/- 0.2%; 19.2 micromol Cr, 6.6 +/- 0.1%). Fasting glucose was lower in the 19.2-micromol group after 2 and 4 months (4-month values: placebo, 8.8 +/- 0.3 mmol/l; 19.2 micromol Cr, 7.1 +/- 0.2 mmol/l). Two-hour glucose values were also significantly lower for the subjects consuming 19.2 micromol supplemental Cr after both 2 and 4 months (4-month values: placebo, 12.3 +/- 0.4 mmo/l; 19.2 micromol Cr, 10.5 +/- 0.2 mmol/l). Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months. Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 micromol/day Cr. These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c, glucose, insulin, and cholesterol variables in subjects with type 2 diabetes. The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake.

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B
Dongping Xu, Junliang Fu, Lei Jin, Hui Zhang +4 more
2006· The Journal of Immunology446doi:10.4049/jimmunol.177.1.739

CD4+CD25+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self and foreign Ags, but their role in persistent viral infection has not been well-defined. In this study, we investigated whether and where CD4+CD25+ Treg contribute to the development of chronic hepatitis B (CHB). One hundred twenty-one patients were enrolled, including 16 patients with acute hepatitis B, 76 with CHB, and 29 with chronic severe hepatitis B. We demonstrated that in chronic severe hepatitis B patients, the frequencies of CD4+CD25+ Treg in both PBMC and liver-infiltrating lymphocytes were significantly increased and there was a dramatic increase of FoxP3(+)-cell and inflammatory cell infiltration in the liver compared with healthy controls. In CHB patients, circulating CD4+CD25+ Treg frequency significantly correlates with serum viral load. In acute hepatitis B patients, circulating CD4+CD25+ Treg frequency was initially low and with time, the profile reversed to exhibit an increased number of circulating Treg in the convalescent phase and restored to normal levels upon resolution. In PBMC taken from infected patients, depletion of CD4+CD25+ Treg led to an increase of IFN-gamma production by HBV-Ag-stimulated PBMC. In addition, CD4+CD25+ Treg were capable of suppressing proliferation of autologous PBMC mediated by HBV Ags, which probably reflects the generation of HBV-Ag-specific Treg in circulation and in the liver of HBV-infected patients. Together, our findings suggest that CD4+CD25+ Treg play an active role not only in modulating effectors of immune response to HBV infection, but also in influencing the disease prognosis in patients with hepatitis B.

Genomic basis for RNA alterations in cancer
PCAWG Transcriptome Core Group, Claudia Calabrese, Natalie R. Davidson, Deniz Demircioğlu +4 more
2020· Nature423doi:10.1038/s41586-020-1970-0

Abstract Transcript alterations often result from somatic changes in cancer genomes 1 . Various forms of RNA alterations have been described in cancer, including overexpression 2 , altered splicing 3 and gene fusions 4 ; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) 5 . Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis , of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed ‘bridged’ fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.

Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005–2014
Fupin Hu, Yan Guo, Demei Zhu, F. Wang +4 more
2016· Clinical Microbiology and Infection371doi:10.1016/j.cmi.2016.01.001

With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22,774 and 84,572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.

The Impact of Customer-to-Customer Interaction on Cruise Experience and Vacation Satisfaction
Jue Huang, Cathy H.C. Hsu
2009· Journal of Travel Research369doi:10.1177/0047287509336466

While the role of customer-to-customer (C2C) interaction in shaping service experience has been recognized in the services marketing literature, empirical examination of this issue is limited. Similarly, investigation of tourists’ social contacts has mainly focused on the tourist—local community and tourist—service personnel dyads, while much less is known about tourist-to-tourist interactions. To fill this knowledge gap, this study has examined interaction between tourists on cruise vacations and its impact on the cruise experience and vacation satisfaction. An online survey is conducted with an American online panel ( n = 613). The findings reveal that the quality of C2C interaction has positive direct impacts on the cruise experience as well as indirect effects on vacation satisfaction, mediated by cruise experience. Moreover, the quality of C2C interaction has suppressor effects on the quantity of C2C interaction. The results call for the incorporation of C2C interaction as one component of the relationship marketing theory.

mNGS in clinical microbiology laboratories: on the road to maturity
Dongsheng Han, Ziyang Li, Rui Li, Ping Tan +2 more
2019· Critical Reviews in Microbiology364doi:10.1080/1040841x.2019.1681933

Metagenomic next-generation sequencing (mNGS) is increasingly being applied in clinical laboratories for unbiased culture-independent diagnosis. Whether it can be a next routine pathogen identification tool has become a topic of concern. We review the current implementation of this new technology for infectious disease diagnostics and discuss the feasibility of transforming mNGS into a routine diagnostic test. Since 2008, numerous studies from over 20 countries have revealed the practicality of mNGS in the work-up of undiagnosed infectious diseases. mNGS performs well in identifying rare, novel, difficult-to-detect and coinfected pathogens directly from clinical samples and presents great potential in resistance prediction by sequencing the antibiotic resistance genes, providing new diagnostic evidence that can be used to guide treatment options and improve antibiotic stewardship. Many physicians recognized mNGS as a last resort method to address clinical infection problems. Although several hurdles, such as workflow validation, quality control, method standardisation, and data interpretation, remain before mNGS can be implemented routinely in clinical laboratories, they are temporary and can be overcome by rapidly evolving technologies. With more validated workflows, lower cost and turnaround time, and simplified interpretation criteria, mNGS will be widely accepted in clinical practice. Overall, mNGS is transforming the landscape of clinical microbiology laboratories, and to ensure that it is properly utilised in clinical diagnosis, both physicians and microbiologists should have a thorough understanding of the power and limitations of this method.

Tannic acid-based metal phenolic networks for bio-applications: a review
Zhenhu Guo, Wensheng Xie, Jingsong Lu, Xiaoxiao Guo +4 more
2021· Journal of Materials Chemistry B345doi:10.1039/d1tb00383f

Tannic acid (TA), a large polyphenolic molecule, has long been known for use in food additives, antioxidants, bio-sorbents, animal feed and adhesives due to its intrinsic properties such as antioxidation, metal chelation, and polymerization. Recently, there has been a renewed interest in fabricating engineered advanced materials with TA modification for novel bio-applications. The modification process involves various interactions/reactions based on its diverse chemical structure, contributed by abundant aromatic rings and hydroxyl groups. In addition, the obtained composites are endowed with retained TA activity and novel enhanced properties. Therefore, the aim of this review is to highlight the recent biomedical application of TA-based metal phenolic networks (TA-MPNs) by focusing on their intrinsic properties and the endowed ability for novel engineered functional composites. The potential contributions of TA-MPNs in "Tumor Theranostics", "Anti-Bacterial Ability", "Wound Repair for Skin Regeneration" and "Bone Tissue Regeneration Applications" are summarized in this paper.

A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of the Effects of Qili Qiangxin Capsules in Patients With Chronic Heart Failure
Xinli Li, Jian Zhang, Jun Huang, Aiqun Ma +4 more
2013· Journal of the American College of Cardiology338doi:10.1016/j.jacc.2013.05.035

OBJECTIVES: The purpose of this study was to assess the effects of qili qiangxin capsules in patients with chronic heart failure (CHF). BACKGROUND: Qili qiangxin capsules are a traditional Chinese medicine that has been approved in China for the treatment of CHF, but the evidence supporting its efficacy remains unclear. METHODS: A total of 512 patients with CHF were enrolled and randomly assigned to receive the placebo or qili qiangxin capsules in addition to their standard medications for the treatment of CHF. The primary endpoint was the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level during 12 weeks of treatment. RESULTS: At the 12-week follow-up, a significant reduction in the NT-proBNP level from baseline was observed in both groups, but the qili qiangxin capsule group demonstrated a significantly greater reduction than the placebo group (p = 0.002); 47.95% of patients in the qili qiangxin capsule group demonstrated reductions in NT-proBNP levels of at least 30% compared with 31.98% of patients in the placebo group (p < 0.001). Treatment with qili qiangxin capsules also demonstrated superior performance in comparison to the placebo with respect to New York Heart Association functional classification, left ventricular ejection fraction, 6-min walking distance, and quality of life. CONCLUSIONS: On a background of standard treatment, qili qiangxin capsules further reduced the levels of NT-proBNP. Together, our data suggest that qili qiangxin capsules could be used in combination therapy for CHF.

SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2
Huize Pan, Di Guan, Xiaomeng Liu, Jingyi Li +4 more
2016· Cell Research335doi:10.1038/cr.2016.4

SIRT6 belongs to the mammalian homologs of Sir2 histone NAD(+)-dependent deacylase family. In rodents, SIRT6 deficiency leads to aging-associated degeneration of mesodermal tissues. It remains unknown whether human SIRT6 has a direct role in maintaining the homeostasis of mesodermal tissues. To this end, we generated SIRT6 knockout human mesenchymal stem cells (hMSCs) by targeted gene editing. SIRT6-deficient hMSCs exhibited accelerated functional decay, a feature distinct from typical premature cellular senescence. Rather than compromised chromosomal stability, SIRT6-null hMSCs were predominately characterized by dysregulated redox metabolism and increased sensitivity to the oxidative stress. In addition, we found SIRT6 in a protein complex with both nuclear factor erythroid 2-related factor 2 (NRF2) and RNA polymerase II, which was required for the transactivation of NRF2-regulated antioxidant genes, including heme oxygenase 1 (HO-1). Overexpression of HO-1 in SIRT6-null hMSCs rescued premature cellular attrition. Our study uncovers a novel function of SIRT6 in maintaining hMSC homeostasis by serving as a NRF2 coactivator, which represents a new layer of regulation of oxidative stress-associated stem cell decay.

The Effects of Palmitate on Hepatic Insulin Resistance Are Mediated by NADPH Oxidase 3-derived Reactive Oxygen Species through JNK and p38MAPK Pathways
Dan Gao, Shanwei Nong, Xiuqing Huang, Yonggang Lu +4 more
2010· Journal of Biological Chemistry329doi:10.1074/jbc.m110.128694

Elevated plasma free fatty acid (FFA) levels in obesity may play a pathogenic role in the development of insulin resistance. However, molecular mechanisms linking FFA to insulin resistance remain poorly understood. Oxidative stress acts as a link between FFA and hepatic insulin resistance. NADPH oxidase 3 (NOX3)-derived reactive oxygen species (ROS) may mediate the effect of TNF-α on hepatocytes, in particular the drop in cellular glycogen content. In the present study, we define the critical role of NOX3-derived ROS in insulin resistance in db/db mice and HepG2 cells treated with palmitate. The db/db mice displayed increased serum FFA levels, excess generation of ROS, and up-regulation of NOX3 expression, accompanied by increased lipid accumulation and impaired glycogen content in the liver. Similar results were obtained from palmitate-treated HepG2 cells. The exposure of palmitate elevated ROS production and NOX3 expression and, in turn, increased gluconeogenesis and reduced glycogen content in HepG2 cells. We found that palmitate induced hepatic insulin resistance through JNK and p38MAPK pathways, which are rescued by siRNA-mediated NOX3 reduction. In conclusion, our data demonstrate a critical role of NOX3-derived ROS in palmitate-induced insulin resistance in hepatocytes, indicating that NOX3 is the predominant source of palmitate-induced ROS generation and that NOX3-derived ROS may drive palmitate-induced hepatic insulin resistance through JNK and p38MAPK pathways. Elevated plasma free fatty acid (FFA) levels in obesity may play a pathogenic role in the development of insulin resistance. However, molecular mechanisms linking FFA to insulin resistance remain poorly understood. Oxidative stress acts as a link between FFA and hepatic insulin resistance. NADPH oxidase 3 (NOX3)-derived reactive oxygen species (ROS) may mediate the effect of TNF-α on hepatocytes, in particular the drop in cellular glycogen content. In the present study, we define the critical role of NOX3-derived ROS in insulin resistance in db/db mice and HepG2 cells treated with palmitate. The db/db mice displayed increased serum FFA levels, excess generation of ROS, and up-regulation of NOX3 expression, accompanied by increased lipid accumulation and impaired glycogen content in the liver. Similar results were obtained from palmitate-treated HepG2 cells. The exposure of palmitate elevated ROS production and NOX3 expression and, in turn, increased gluconeogenesis and reduced glycogen content in HepG2 cells. We found that palmitate induced hepatic insulin resistance through JNK and p38MAPK pathways, which are rescued by siRNA-mediated NOX3 reduction. In conclusion, our data demonstrate a critical role of NOX3-derived ROS in palmitate-induced insulin resistance in hepatocytes, indicating that NOX3 is the predominant source of palmitate-induced ROS generation and that NOX3-derived ROS may drive palmitate-induced hepatic insulin resistance through JNK and p38MAPK pathways.

Laboratory testing of SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 (2019‐nCoV): Current status, challenges, and countermeasures
Ying Yan, Le Chang, Lunan Wang
2020· Reviews in Medical Virology328doi:10.1002/rmv.2106

Emerging and reemerging infectious diseases are global public concerns. With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, SARS-CoV-2 has been attracting tremendous attention. Rapid and accurate laboratory testing of SARS-CoV-2 is essential for early discovery, early reporting, early quarantine, early treatment, and cutting off epidemic transmission. The genome structure, transmission, and pathogenesis of SARS-CoV-2 are basically similar to SARS-CoV and MERS-CoV, the other two beta-CoVs of medical importance. During the SARS-CoV and MERS-CoV epidemics, a variety of molecular and serological diagnostic assays were established and should be referred to for SARS-CoV-2. In this review, by summarizing the articles and guidelines about specimen collection, nucleic acid tests (NAT) and serological tests for SARS-CoV, MERS-CoV, and SARS-CoV-2, several suggestions are put forward to improve the laboratory testing of SARS-CoV-2. In summary, for NAT: collecting stool and blood samples at later periods of illness to improve the positive rate if lower respiratory tract specimens are unavailable; increasing template volume to raise the sensitivity of detection; putting samples in reagents containing guanidine salt to inactivate virus as well as protect RNA; setting proper positive, negative and inhibition controls to ensure high-quality results; simultaneously amplifying human RNase P gene to avoid false-negative results. For antibody test, diverse assays targeting different antigens, and collecting paired samples are needed.

Standards of care for type 2 diabetes in China
Jianping Weng, Linong Ji, Weiping Jia, Juming Lu +4 more
2016· Diabetes/Metabolism Research and Reviews323doi:10.1002/dmrr.2827

The past 30 years have witnessed significant increases in the prevalence of type 2 diabetes mellitus (T2DM) in China. A 1980 epidemiological survey that included 30 000 people from 14 provinces and cities nationwide indicated that the prevalence of diabetes was 0.67% 1. A 1994–1995 epidemiological survey that included 210 000 people from 19 provinces and cities found that the prevalence of diabetes was 2.5% among individuals who were 25–64 years old (with a population standardized rate of 2.2%) and that the prevalence of impaired glucose tolerance was 3.2% (with a population standardized rate of 2.1%) 2. A national nutrition survey conducted in 2002, showed that the prevalences of diabetes were 4.5% and 1.8% among people over 18 years in the urban and rural areas, respectively 3. In 2007–2008, the Chinese Diabetes Society (CDS) performed an epidemiological survey in 14 provinces and cities nationwide. After adopting a weighted analysis that took into account factors such as gender, age, rural and urban distributions and regional differences, the estimated prevalence of diabetes was 9.7% in adults over 20 years of age in China 4, accounting for 92.4 million adults with diabetes (43.1 million rural residents and 49.3 urban residents) (Table 1). This guideline recommends the World Health Organization's (WHO) (1999) the criteria for diagnosis and classification of diabetes, and classification of metabolic status (Table 2): either the fasting plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oral glucose tolerance test (OGTT) can be used alone for epidemiological investigations or mass screenings 7. However, the data in China include only the FPG levels, resulting in a larger proportion of diabetes being missed. The ideal investigation should simultaneously check FPG and 2-h PG after the glucose load; blood glucose levels at other time points after the OGTT are not used as diagnostic criteria. Individuals with impaired fasting glucose should undergo the OGTT to reduce the number of missed diabetes diagnoses. The 2010 American Diabetes Association guidelines added glycated haemoglobin (HbA1c) ≥6.5% as a diagnostic criterion for diabetes 8. In 2011, the WHO also recommended that wherever conditions permit, countries and regions may consider adopting this cut-off point for diabetes diagnosis 9. However, given that the HbA1c test is not yet commonly applied in China, the insufficient degree of standardization, and the fact that the instruments and quality control for measuring HbA1c are currently unable to meet the current diagnostic standard for diabetes, this guideline does not recommend the use of HbA1c for diagnosis of diabetes in China. Nevertheless, for hospitals that use a standardized HbA1c assay with a normal reference value of 4.0–6.0% and strict quality control, HbA1c ≥6.5% can be used as a reference when diagnosing diabetes. This guideline adopts the diabetes aetiology classification system proposed by the WHO (1999), which divides diabetes into four major categories based on aetiological evidence, that is, T1DM, T2DM, gestational diabetes mellitus (GDM) and special types of diabetes. The goal of primary prevention is to prevent the occurrence of T2DM. Secondary prevention aims to prevent diabetic complications in patients with T2DM. Tertiary prevention aims to delay the progression of diabetic complications, to reduce morbidity and mortality and to improve the patients' quality of life. The risk of T2DM depends primarily on the patient's number and degree of risk factors. Some of these factors cannot be changed, whereas others can (Table 3). Primary prevention efforts for T2DM should adopt hierarchical management approaches based on the differences between the high-risk population and general population. It is not feasible either to screen prediabetes in the entire Chinese population or to systematically identify high risk groups by blood glucose tests, considering the huge population in China. Therefore, the identification of high-risk groups relies primarily on opportunistic screening (e.g. screening that occurs during routine physical examinations or during treatment for other diseases). Screening of diabetes benefits the early diagnosis of diabetes and improves the prevention and treatment of diabetes and its complications. Therefore, when conditions permit, high-risk groups should be targeted for diabetes screening. Definition of the high-risk diabetes group among adults are as follows: adults (>18 years) with one or more of the following diabetes risk factors: (1) age ≥40 years, (2) history of impaired glucose regulation, (3) overweight (BMI ≥24 kg/m2) or obesity (BMI ≥28 kg/m2) and/or central obesity (male waist circumference ≥90 cm and female waist circumference ≥85 cm), (4) sedentary lifestyle, (5) first-degree relatives with T2DM, (6) women who delivered a baby weighing ≥4 kg) or were diagnosed with GDM (7) hypertension [systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg (1 mmHg = 0.133 kPa)] or on therapy for hypertension, (8) dyslipidemia [high-density lipoprotein cholesterol (HDL-C) ≤0.91 mmol/L (≤35 mg/dL) and triglycerides ≥2.22 mmol/L (≥200 mg/dL)] or on therapy for hyperlipidemia, (9) atherosclerotic cardiovascular disease, (10) a transient history of steroid diabetes, (11) polycystic ovary syndrome and (12) long-term use of antipsychotics and/or antidepressant treatment. Of the aforementioned factors, impaired glucose regulation is the most important high-risk factor: approximately 5%–10.0% of patients with impaired glucose tolerance progress to T2DM annually 10. For adults in the high-risk group, diabetes screening should be performed as early as possible, regardless of age; for populations with no diabetes risk factors other than age, screening should begin at ≥40 years of age. For children and adolescents at a high risk for diabetes, screening should begin at age 10 years; however, for individuals with an earlier onset of puberty, this guideline recommends that screening starts at puberty. Those whose initial screening results are normal are recommended to undergo screening again at least once every 3 years. At medical institutions with a qualified laboratory, diabetes screening is recommended for high-risk patients during their visits or physical examinations. The fasting blood glucose test is a simple diabetes screening method that should be used for routine screening, albeit there's risk of missing diagnosis. When conditions permit, the OGTT (both FPG and 2-h PG after glucose load) should be performed as often as possible. HbA1c testing is not currently recommended as a routine screening method. To improve the effectiveness of diabetes screening for the general population, targeted diabetes screening should occur according to the individual's degree of diabetes risk. Multiple randomized and controlled studies have shown that people with impaired glucose tolerance can be delayed or prevented from developing to T2DM, through appropriate lifestyle interventions, 11-13. In a study conducted in Daqing, China, patients in the lifestyle intervention group were asked to increase vegetable intake and reduce intake of alcohol and monosaccharides, and those who were defined as overweight or obese (BMI >25 kg/m2) were encouraged to lose weight, increase intensity of physical activity by performing at least 30 min of moderately intense activity per day. After a 6-year lifestyle intervention, the cumulative incidence of T2DM risk for the subsequent 14 years decreased by 43% 14. The lifestyle intervention groups in the Finnish Diabetes Prevention Study 15 and the American Diabetes Prevention Program 16 also demonstrated that the intervention could significantly reduce the risk of developing T2DM among patients with impaired glucose tolerance. This guideline recommends that patients with prediabetes lower the risk of diabetes through diet control and exercise; that patients should receive regular follow-up that provides psychosocial support to ensure patients' long-term adherence to a healthy lifestyle; that blood glucose levels should be regularly tested; that the cardiovascular disease risk factors (such as smoking, hypertension and dyslipidemia) should be closely monitored; and that appropriate intervention measures should be provided. The specific objectives are (1) the BMI of overweight or obese patients should be lowered to approximately 24 kg/m2 or weight loss of at least 5–10% should be achieved, (2) the patients' total daily caloric intake should be reduced by at least 400–500 kcal (1 kcal = 4.184 kJ), (3) the patients' saturated fatty acid intake should be less than 30% of their total fatty acid intake and (4) the patients should be encouraged to engage in moderate-intensity physical activity for at least 150 min/week. Drug intervention trials in a pre-diabetic population showed that the oral administration of hypoglycaemic agents, such as metformin, α-glucosidase inhibitors, thiazolidinediones (TZDs), metformin combined with TZDs, the diet pill orlistat and traditional Chinese herbal medicine (Tianqi capsules), reduced the risk of diabetes 13, 17-21. However, because there is no sufficient evidence showing that drug interventions have long-term efficacy and/or health economics benefits, the clinical guidelines developed by various countries have not widely recommended medical interventions as the primary prevention for diabetes. Given that economic development in China is still in the preliminary stage and significant regional imbalances exist and that diabetes prevention-related health care is currently unsophisticated and imperfect, this guideline currently does not recommend the use of drug interventions to prevent diabetes. The clinical trials on intensive glucose control, such as the Diabetes Control and Complications Trial (DCCT) 22, the United Kingdom Prospective Diabetes Study (UKPDS) 23 and the Kumamoto Study in Japan 24, found that among patients in the early stage of diabetes, intensive glucose control can significantly reduce the risk of diabetic The study also showed that in obese or overweight the use of metformin was with a significant in the risk of and The long-term follow-up studies of the and populations indicated that early intensive control was with a in diabetic and a significant in the of and results evidence that intensive blood glucose control during the early of T2DM can reduce the of diabetic and This guideline recommends that for diagnosed diabetes patients and early T2DM strict control should be to reduce the risk of diabetic complications. The study showed that in patients diagnosed with diabetes, intensive blood pressure control not only significantly reduced the risk of diabetic also the risk of analysis of a in a of therapy and other clinical trials of therapy also showed that intensive blood pressure control reduced the risk of cardiovascular in diabetic patients significant complications The analysis of diabetic patients the Diabetes Study and other clinical studies indicated that the use of to lower lipoprotein cholesterol could reduce the risk of cardiovascular in diabetic patients significant complications. The to Control in Diabetes study showed that the of and drug not cardiovascular benefits, as with alone The results of clinical trials for the primary prevention of cardiovascular in diabetic patients a in the primary prevention of cardiovascular in diabetes patients Nevertheless, a of clinical trials demonstrated that among patients with T2DM and cardiovascular disease risk factors, showed a cardiovascular This guideline recommends that for T2DM patients significant diabetic complications with risk factors for cardiovascular blood blood pressure and to reduce and therapy are to prevent cardiovascular and diabetic The clinical in intensive glucose control trials such as The in Diabetes and and and the Diabetes Trial that intensive glucose control reduced the progression of diabetic (e.g. diabetic and 22, 24, patients who have developed diabetic clinical evidence is still to intensive glucose control measures can reduce the of and The results of clinical trials such as and that for patients with a of diabetes, who are in age and who have cardiovascular risk factors or cardiovascular the use of intensive glucose control measures does not reduce the of cardiovascular and the study showed that in the aforementioned population, intensive glucose control was with an risk of mortality This guideline recommends that for patients who are and who have a diabetes and cardiovascular the and of adopting intensive glucose control be In an should be used a diabetes management system should be developed to control is sufficient clinical evidence that in patients with T2DM who have cardiovascular blood or the use of therapy alone or in can reduce the risk of cardiovascular disease and In patients with diabetic the use of blood agents, the use of or significantly reduced the risk of diabetic progression This guideline recommends that for patients who have a diabetes and cardiovascular disease, in of control, measures such as blood to reduce and should be used to reduce the risk of cardiovascular and and to reduce the risk of diabetic The of and in diabetic patients are significantly than in and these in diabetic patients depends not only on high blood glucose also on other cardiovascular disease risk factors and In to drug diabetes control also blood glucose and other cardiovascular risk factors as to the control the or the treatment be as diabetes is a disease, the and are to diabetes diabetes control is not a treatment in the traditional a management in The ideal control of T2DM according to the age, and complications of patients (Table A treatment that does not the control should not be as a because in the control benefits to the and the with for in HbA1c are closely with in complications and The primary for the for T2DM control is which should consider age, disease of complications or and other factors of is a of diabetes. patients and those with a disease may not treatment to reduce blood pressure to mmHg or The blood pressure value for patients may be to T2DM is a The blood glucose to increase as the disease the intensity of control treatment should be intervention is the for T2DM treatment and should be applied the diabetes treatment When lifestyle alone is unable to blood glucose drug treatment should be The drug for T2DM is no are metformin should of the diabetes treatment who could not metformin may use α-glucosidase or When metformin alone is unable to blood glucose α-glucosidase inhibitors, or can be who could not metformin may undergo therapy with other oral When a therapy of types of oral still unable to blood glucose may be added or or or a of types of oral may be can be used as a treatment. When or combined with other oral is still unable to blood glucose the should be to include daily of or When with and use should be on the and the of Diabetes the American Diabetes Association and for Health and the treatment for in T2DM are proposed and shown in 1. with diabetes or prediabetes medical nutrition treatment should be the of a or an management a diabetes who is with diabetes treatment. To the metabolic control for patients and or quality should be In to control the total intake and various in a and the nutrition status should be quality For overweight or obese this guideline recommends weight loss measures combined with physical and to weight loss an important in the management of T2DM. increases control blood cardiovascular risk factors, weight and improves a primary on populations at high risk of diabetes studies have shown that the regular of more than reduced the HbA1c by and that the mortality of diabetes patients who to regular for years significantly diabetic should be to or status and the of should be and for should be and should be to patients nutrition therapy and treatment are for high blood glucose in T2DM. When diet and cannot control the blood glucose oral should be in a T2DM is a the of T2DM, less as T2DM the on control measures treatment often the use of oral and a of oral and (e.g. and is the primary currently used in medical The major of is blood glucose by the glucose and The diabetes treatment guidelines of countries and recommend metformin as the among the and for control of in T2DM of clinical trials have shown that metformin can reduce HbA1c by and can also reduce weight The efficacy of metformin shown to be from the weight The study results showed that metformin also decreased the of cardiovascular and in obese patients with T2DM In China, randomized controlled clinical trials have conducted to the of metformin and on cardiovascular in patients with T2DM combined with disease, and the results showed that metformin treatment was with a significant of major cardiovascular alone not the of metformin and or the risk of The of metformin was with a and the was an to reduce The efficacy of metformin was by weight The between and risk is are in patients with mg/dL) for mg/dL) for women or estimated rate or those major should be for patients with are and their is the by from the blood glucose trials have shown that can reduce HbA1c by At are the primary recommended in the diabetes treatment guidelines of countries and Prospective and randomized clinical studies have shown that the use of was with reduced of diabetic and the in China are and used can to in patients and in those with and may also weight with should use who can once a day. is a drug and various traditional Chinese that have a to that of with a lower risk of and a more of blood glucose primarily by the to the of the in China are and trials have shown that can HbA1c by not when used may increase the risk of when used in with or and are of TZDs, and these are more when are used in with use with increase risk of and with Association classification and disease, the of and and should not are The currently in China are and This of blood glucose by in the early and can lower HbA1c by be a and can be used or in with other The of clinical studies conducted on T2DM patients in China showed that in of was to and and was to α-glucosidase inhibitors, metformin and A of clinical studies of populations with T2DM, Chinese showed that in of than α-glucosidase and was to and For diagnosed T2DM therapy with metformin reduced HbA1c more significantly than alone with a significantly risk of of are and weight the risk and degree of are lower with than with can be used in patients with reduce blood glucose by in the are for patients who as their and In China, α-glucosidase include and of clinical studies conducted on the T2DM population, Chinese showed that α-glucosidase could reduce HbA1c by and weight loss studies of Chinese people with T2DM showed that the hypoglycaemic of a daily of of was to that of a daily of of metformin can be combined with or to α-glucosidase are such as and with a and the are to reduce The use of this alone does not to and may reduce the risk of no in and are for no increase in the incidence of occurs and this is When patients therapy with α-glucosidase glucose or can be used as and have a to levels of by the of in through of in a glucose and the in China include and trials in T2DM patients in China showed that and can reduce HbA1c by and respectively a study showed that the of was to that of and that and can reduce HbA1c by and the of is to the patient's HbA1c that is, the the HbA1c the be reduced by The use of alone does not increase the risk of have a on weight or may increase and not increase the risk of cardiovascular disease, and When or is for patients with the be reduced according to the of When in patients with or are reduce blood glucose by and in a glucose and can delay intake central in the Chinese the are and lower blood and also significantly reduce weight and improve triglycerides and blood alone not significantly increase the risk of trials of patients with T2DM, Chinese showed that the of was to that of to a weight loss of and a in blood pressure of approximately 3 mmHg reduced HbA1c by and weight by may be used alone or in with other oral A number of clinical studies have shown that when used after the of an oral or showed efficacy than the control drug of are (e.g. and which occur in the initial stage of treatment and with treatment time or can be used to intensive therapy for diagnosed T2DM For diagnosed T2DM patients with HbA1c or FPG mmol/L and with intensive therapy may be The appropriate treatment is 2 with a of mmol/L for fasting blood glucose and mmol/L for blood considering the HbA1c as treatment therapy should be combined with medical therapy and diabetes treatment include a or or or a day. For patients who to treatment after intensive the to therapy or to to should be based on the conditions as by a diabetes For patients have the therapy regular (e.g. every 3 follow-up should be blood glucose increases again FPG mmol/L or 2-h PG the should be is a of intensive therapy delivered an The appropriate populations are women with diabetes who are or to women who therapy and patients with T2DM who intensive The treatment are shown in 2. patients may which may and can be a major to the blood glucose and special of diabetic patients from diabetic which is the of in diabetes patients of diabetic is into which are also used for stage rate and stage stage early diabetic with stage clinical diabetic with and stage is an important type of for diabetic the should be the of in Study or the (Table is the most of onset among adults years. with diabetic and may have no clinical in of regular examinations are diabetic patients are recommended to undergo follow-up once every years; patients with should be once a and patients with should be once every The of should be for is according to the after The clinical standard for diabetic is shown in is one of the most complications of diabetes. may the central system more the to or in diabetic patients that cannot be to other is a diabetic The diagnosis of other diabetic relies on the screening of clinical or (1) blood glucose control, of dyslipidemia and hypertension (2) disease screening and patients should undergo screening for diabetic at least once a after the diagnosis of diabetes. For patients with a of diabetes or complications, such as and should occur every (3) patients from should receive care to reduce the incidence of (1) (2) commonly used such as and factors, may be (3) commonly used such as may be (4) commonly used include and blood for the treatment of diabetic include and and and and disease to is not a specific to diabetes, the risk of disease in patients with diabetes significantly increases with patients diabetes. In patients with diabetes also have an earlier age of onset and of lower disease, as as more and disease is a of disease that as lower or For diabetes patients over age of years, screening should be conducted For diabetes patients with risk factors (e.g. cardiovascular disease, hypertension, or a diabetes of more than years) should be at least once a For diabetes patients with and regardless of their age, a and of disease should be (1) the a regardless of the of lower a diagnosis should be (2) For a who and a by after a a diagnosis should be (3) the a or pressure mmHg or pressure a diagnosis should be The to the prevention of atherosclerotic disease the prevention of cardiovascular the prevention of and the prevention of or the of the and the of the status of patients with Therefore, the standard treatment for diabetic of primary prevention prevent or delay the occurrence of prevention and delay and prevention and reduce and cardiovascular Diabetes is an risk for cardiovascular and with diabetes have risk of cardiovascular and with patients diabetes. FPG and are with an risk of cardiovascular and when not the diagnostic criteria for diabetes. patients often important risk factors for cardiovascular and such as dyslipidemia and hypertension evidence that strict control in patients with T2DM a on the of cardiovascular and and from those among patients with a disease who are and who have a history of cardiovascular or cardiovascular risk factors However, the management of risk factors can significantly the risk of cardiovascular and and from those in patients with diabetes. Therefore, the prevention of diabetic the and control of cardiovascular disease risk factors (e.g. high blood hypertension and dyslipidemia) and appropriate At the incidence of cardiovascular risk factors is high among T2DM patients in China, and are with T2DM, only for blood and total cholesterol The use of also more screening and treatment of cardiovascular risk factors and an rate of therapy are The clinical for screening and the and for patients with T2DM are shown in 3. to an epidemiological analysis of metabolic syndrome in the current Chinese population, this guideline the of the metabolic syndrome based on the The diagnostic criteria are as follows: (1) waist ≥90 cm and women ≥85 (2) high blood fasting blood glucose mmol/L or glucose at 2 after glucose mmol/L and/or diabetes diagnosis and (3) high blood blood pressure mmHg and/or diagnosed and on (4) fasting mmol/L and (5) fasting with or more of the aforementioned are diagnosed with metabolic

Possible Pathogenesis of Painful Intervertebral Disc Degeneration
Baogan Peng, Jianhua Hao, Shuxun Hou, Wenwen Wu +3 more
2006· Spine319doi:10.1097/01.brs.0000201324.45537.46

In Brief Study Design. We collected the specimens of lumbar intervertebral disc (i.e., the symptomatic degenerative disc) from patients with discogenic low back pain to study the histopathologic features and growth factor expressions. Objectives. To study the pathogenesis of disc degeneration, meanwhile discriminating between common disc degeneration (aging disc) (i.e., black asymptomatic disc, not clinically relevant) and painful disc degeneration (i.e., symptomatic disc, clinically relevant). Summary of Background Data. The pathogenesis of intervertebral disc degeneration is poorly understood, mainly because of the difficulty to establish the experimental model with good reproducibility. Recently, the popularity of spinal fusion leads to more opportunities to obtain disc specimens, which could be applied to explore the pathogenesis of disc degeneration with modern biologic techniques. Methods. There were 21 specimens of lumbar intervertebral discs from 15 patients with discogenic low back pain during posterior lumbar interbody fusion, 16 aging discs from patients without low back pain, and 10 normal discs as control collected for the study of their histopathologic features, as well as the expressions of basic fibroblast growth factor (bFGF) and its receptor (Flg), transforming growth factor-β1 (TGF-β1) and its receptor (TGF-βRI) by immunohistochemistry. The distribution of macrophages and mast cells was also noted. Proliferating cell nuclear antigen was assessed to evaluate proliferating activities of disc cells. Results. The distinct histologic characteristic of the disc from the patient with discogenic low back pain was the ingrowth of vascularized granulation tissue along torn fissures, extending from the external layer of the anulus fibrosus into the nucleus pulposus. The immunohistochemical staining showed that there were strong expressions of bFGF and TGF-β1 and their receptors, as well as a strong expression of proliferating cell nuclear antigen in the zones of granulation tissue in the painful discs. However, there were only weak expressions in the nongranulation tissue zones in the painful discs and aging discs, and no expression in the control discs. In addition, abundant macrophages and mast cells were found in the granulation tissue zones of painful discs but absent in the nongranulation tissue zones of painful discs or aging discs and the normal control discs. Conclusions. The findings indicated that degeneration of the painful disc might originate from the injury and subsequent repair of anulus fibrosus. Growth factors, such as bFGF and TGF-β1, macrophages and mast cells might play a key role in the repair of the injured anulus fibrosus and subsequent disc degeneration. There were 21 specimens of painful lumbar intervertebral discs collected for the study of the pathogenesis of disc degeneration. The studies found that the distinct histologic characteristic of the painful disc was the ingrowth of vascularized granulation tissue along torn fissures, extending from the external layer of the anulus fibrosus into the nucleus pulposus. There were strong expressions of basic fibroblast growth factor and transforming growth factor-β1 and their receptors, as well as a strong expression of proliferating cell nuclear antigen in the zones of granulation tissue in the painful discs. In addition, abundant macrophages and mast cells were found in the same area. The findings indicated that the degeneration of painful disc might originate from the injury and subsequent repair of anulus fibrosus.

Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019
Mingzhang Zuo, Yuguang Huang, Wuhua Ma, Zhanggang Xue +3 more
2020· Chinese Medical Sciences Journal302doi:10.24920/003724

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.

Pan-cancer circulating tumor DNA detection in over 10,000 Chinese patients
Yongliang Zhang, Yu Yao, Yaping Xu, Lifeng Li +4 more
2021· Nature Communications289doi:10.1038/s41467-020-20162-8

Abstract Circulating tumor DNA (ctDNA) provides a noninvasive approach to elucidate a patient’s genomic landscape and actionable information. Here, we design a ctDNA-based study of over 10,000 pan-cancer Chinese patients. Using parallel sequencing between plasma and white blood cells, 14% of plasma cell-free DNA samples contain clonal hematopoiesis (CH) variants, for which detectability increases with age. After eliminating CH variants, ctDNA is detected in 73.5% of plasma samples, with small cell lung cancer (91.1%) and prostate cancer (87.9%) showing the highest detectability. The landscape of putative driver genes revealed by ctDNA profiling is similar to that in a tissue-based database (R 2 = 0.87, p &lt; 0.001) but also shows some discrepancies, such as higher EGFR (44.8% versus 25.2%) and lower KRAS (6.8% versus 27.2%) frequencies in non-small cell lung cancer, and a higher TP53 frequency in hepatocellular carcinoma (53.1% versus 28.6%). Up to 41.2% of plasma samples harbor drug-sensitive alterations. These findings may be helpful for identifying therapeutic targets and combined treatment strategies.