First Affiliated Hospital of Fujian Medical University

Comorbidities are associated with the severity of coronavirus disease 2019 (COVID-19). This meta-analysis aimed to explore the risk of severe COVID-19 in patients with pre-existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history. A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases. The languages of literature included English and Chinese. The point prevalence of severe COVID-19 in patients with pre-existing COPD and those with ongoing smoking was evaluated with this meta-analysis. Overall 11 case series, published either in Chinese or English language with a total of 2002 cases, were included in this study. The pooled OR of COPD and the development of severe COVID-19 was 4.38 (fixed-effects model; 95% CI: 2.34-8.20), while the OR of ongoing smoking was 1.98 (fixed-effects model; 95% CI: 1.29-3.05). There was no publication bias as examined by the funnel plot and Egger's test (P = not significant). The heterogeneity of included studies was moderate for both COPD and ongoing smoking history on the severity of COVID-19. COPD and ongoing smoking history attribute to the worse progression and outcome of COVID-19.

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.

Although amyloid-beta peptide (Abeta) is the neurotoxic species implicated in the pathogenesis of Alzheimer's disease (AD), mechanisms through which intracellular Abeta impairs cellular properties, resulting in neuronal dysfunction, remain to be clarified. Here we demonstrate that intracellular Abeta is present in mitochondria from brains of transgenic mice with targeted neuronal overexpression of mutant human amyloid precursor protein and AD patients. Abeta progressively accumulates in mitochondria and is associated with diminished enzymatic activity of respiratory chain complexes (III and IV) and a reduction in the rate of oxygen consumption. Importantly, mitochondria-associated Abeta, principally Abeta42, was detected as early as 4 months, before extensive extracellular Abeta deposits. Our studies delineate a new means through which Abeta potentially impairs neuronal energetics, contributing to cellular dysfunction in AD.

Falling poses a major threat to the steadily growing population of the elderly in modern-day society. A major challenge in the prevention of falls is the identification of individuals who are at risk of falling owing to an unstable gait. At present, several methods are available for estimating gait stability, each with its own advantages and disadvantages. In this paper, we review the currently available measures: the maximum Lyapunov exponent (λS and λL), the maximum Floquet multiplier, variability measures, long-range correlations, extrapolated centre of mass, stabilizing and destabilizing forces, foot placement estimator, gait sensitivity norm and maximum allowable perturbation. We explain what these measures represent and how they are calculated, and we assess their validity, divided up into construct validity, predictive validity in simple models, convergent validity in experimental studies, and predictive validity in observational studies. We conclude that (i) the validity of variability measures and λS is best supported across all levels, (ii) the maximum Floquet multiplier and λL have good construct validity, but negative predictive validity in models, negative convergent validity and (for λL) negative predictive validity in observational studies, (iii) long-range correlations lack construct validity and predictive validity in models and have negative convergent validity, and (iv) measures derived from perturbation experiments have good construct validity, but data are lacking on convergent validity in experimental studies and predictive validity in observational studies. In closing, directions for future research on dynamic gait stability are discussed.

Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low 5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2050, with the average annual growth of 1.1%, meaning that pancreatic cancer will pose a significant public health burden. Due to the special anatomical location of the pancreas, the development of pancreatic cancer is usually diagnosed at a late stage with obvious clinical symptoms. Therefore, a comprehensive understanding of the risk factors for pancreatic cancer is of great clinical significance for effective prevention of pancreatic cancer. In this paper, the epidemiological characteristics, developmental trends, and risk factors of pancreatic cancer are reviewed and analyzed in detail.

Importance: Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited. Objective: To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations. Design, Setting, and Participants: This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China. Main Outcomes and Measures: Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases. Results: The study included 676 394 Chinese adults (395 122 [58.4%] females; mean [SD] age, 59.7 [11.0] years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% [95% CI, 2.6%-2.7%] vs 2.5% [95% CI, 2.5%-2.6%]; P = .02), but the incidence rate (485.5 [95% CI, 462.8-508.3] vs 520.8 [95% CI, 496.3-545.2] per 100 000 person-years; P < .001) and mortality rate (309.9 [95% CI, 291.7-328.1] vs 369.7 [95% CI, 349.1-390.3] per 100 000 person-years; P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 [95% CI, 3.09-3.32]). Conclusions and Relevance: In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.

The programmed cell death protein 1 (PD-1) pathway has received considerable attention due to its role in eliciting the immune checkpoint response of T cells, resulting in tumor cells capable of evading immune surveillance and being highly refractory to conventional chemotherapy. Application of anti-PD-1/PD-L1 antibodies as checkpoint inhibitors is rapidly becoming a promising therapeutic approach in treating tumors, and some of them have successfully been commercialized in the past few years. However, not all patients show complete responses and adverse events have been noted, suggesting a better understanding of PD-1 pathway mediated immunosuppression is needed to predict patient response and improve treatment efficacy. Here, we review the progresses on the studies of the mechanistic role of PD-1 pathway in the tumor immune evasion, recent clinical development and commercialization of PD-1 pathway inhibitors, the toxicities associated with PD-1 blockade observed in clinical trials as well as how to improve therapeutic efficacy and safety of cancer immunotherapy.

ObjectivesCoronavirus Disease 2019 (COVID-19) is a new respiratory and systemic disease which needs quick identification of potential critical patients. This meta-analysis aimed to explore the relationship between lymphocyte count and the severity of COVID-19.MethodsA comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases. The language of literatures included English and Chinese. Mean difference (MD) of lymphocyte count in COVID-19 patients with or without severe disease and odds ratio (OR) of lymphopenia for severe form of COVID-19 was evaluated with this meta-analysis.ResultsOverall 13 case-series with a total of 2282 cases were included in the study. The pooled analysis showed that lymphocyte count was significantly lower in severe COVID-19 patients (MD -0.31 × 109/L; 95%CI: -0.42 to -0.19 × 109/L). The presence of lymphopenia was associated with nearly threefold increased risk of severe COVID-19 (Random effects model, OR = 2.99, 95% CI: 1.31-6.82).ConclusionsLymphopenia is a prominent part of severe COVID-19 and a lymphocyte count of less than 1.5 × 109/L may be useful in predicting the severity clinical outcomes.

BACKGROUND AND AIMS: Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020, the utility of which has not been tested and validated in real world. We aimed to compare the characteristics of MAFLD and non-alcoholic fatty liver disease (NAFLD). METHODS: The data was retrieved from the third National Health and Nutrition Examination Surveys of the United States, which is an unbiased survey dataset and frequently used for the study of fatty liver disease. RESULTS: A total of 13 083 cases with completed ultrasonography and laboratory data were identified from the NHANES III database. MAFLD was diagnosed in 4087/13 083 (31.24%) participants, while NAFLD in 4347/13 083 (33.23%) amongst the overall population and 4347/12 045 (36.09%) in patients without alcohol intake and other liver diseases. Compared with NAFLD, MAFLD patients were significantly older, had higher BMI level, higher proportions of metabolic comorbidities (diabetes, hypertension) and higher HOMA-IR, lipid and liver enzymes. MAFLD patients with alcohol consumption were younger than those without, and more likely to be male. They had less metabolic disorder but higher liver enzymes. There were more cases with advance fibrosis in MAFLD patients with alcohol consumption. CONCLUSION: MAFLD definition is more practical for identifying patients with fatty liver disease with high risk of disease progression.

IMPORTANCE: Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel. OBJECTIVE: To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. DESIGN, SETTING, AND PARTICIPANTS: Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012. INTERVENTIONS: Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome. RESULTS: Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction). CONCLUSIONS AND RELEVANCE: Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00979589.

Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

In this work, an innovative enzyme-free colorimetric immunoassay was proposed for the sensitive detection of alpha-fetoprotein (AFP) by introducing thymolphthalein-modified metal-polydopamine framework (MPDA@TP) for the signal generation and amplification. Using zeolitic imidazolate framework (ZIF-67) as the template, the hollow-structured metal-polydopamine framework (MPDA) with high surface recovery and abundant groups was synthesized and functionalized with thymolphthalein (TP) molecules via typical π-stacking reaction. In the presence of target AFP, an MPDA@TP-linked immunosorbent assay (MLISA) was implemented on the capture antibody-modified microplate by using detection antibody-labeled MPDA@TP as the secondary antibody. Upon alkaline solution introduction, the coated hydrophobic TP on the MPDA was deprotonated into hydrophilic TP2– ion and dissolved in the solution, thereby resulting in the color change of the solution from nearly colorless to deep blue, and the increasing absorbance of the solution at 595 nm. Importantly, the MPDA@TP-based immunoassay could exhibit high sensitivity for the quantitative detection of target AFP on the basis of the absorbance within a linear range of 10–1000 pg mL–1 at a low detection limit of 2.3 pg mL–1. Furthermore, this system was validated preliminarily to screen human serum specimens with well-matched results for the referenced AFP ELISA kit. Taking advantage of simplicity, enzyme-free, convenience, and sensitivity, MPDA@TP-linked immunosorbent assay has the potential for the application in scientific research and clinical diagnosis.

The coronavirus disease 2019 (COVID-19) has evolved into a pandemic rapidly. Most of the literature show that the elevated liver enzymes in COVID-19 are of little clinical significance. Lower albumin level is seen in severe COVID-19 and is not parallel to the changes in alanine aminotransferase and aspartate aminotransferase levels. We aimed to explore the impact of hypoalbuminemia in COVID-19. This retrospective cohort study included adult patients with confirmed COVID-19. The relationship between hypoalbuminemia and death was studied using binary logistic analysis. A total of 299 adult patients were included, 160 (53.5%) were males and the average age was 53.4 ± 16.7 years. The median time from the onset of illness to admission was 3 days (interquartile ranges, 2-5). Approximately one-third of the patients had comorbidities. Hypoalbuminemia (<35 g/L) was found in 106 (35.5%) patients. The difference in albumin was considerable between survivors and non-survivors (37.6 ± 6.2 vs 30.5 ± 4.0, P < .001). Serum albumin level was inversely correlated to white blood cell (r = -.149, P = .01) and neutrophil to lymphocyte ratio (r = -.298, P < .001). Multivariate analysis showed the presence of comorbidities (OR, 6.816; 95% CI, 1.361-34.133), lymphopenia (OR, 13.130; 95% CI, 1.632-105.658) and hypoalbuminemia (OR, 6.394; 95% CI, 1.315-31.092) were independent predictive factors for mortality. In conclusion, hypoalbuminemia is associated with the outcome of COVID-19. The potential therapeutic value of albumin infusion in COVID-19 should be further explored at the earliest.

Background Nasopharyngeal carcinoma (NPC) may be cured with radiation therapy. Tumor proximity to critical structures demands accuracy in tumor delineation to avoid toxicities from radiation therapy; however, tumor target contouring for head and neck radiation therapy is labor intensive and highly variable among radiation oncologists. Purpose To construct and validate an artificial intelligence (AI) contouring tool to automate primary gross tumor volume (GTV) contouring in patients with NPC. Materials and Methods In this retrospective study, MRI data sets covering the nasopharynx from 1021 patients (median age, 47 years; 751 male, 270 female) with NPC between September 2016 and September 2017 were collected and divided into training, validation, and testing cohorts of 715, 103, and 203 patients, respectively. GTV contours were delineated for 1021 patients and were defined by consensus of two experts. A three-dimensional convolutional neural network was applied to 818 training and validation MRI data sets to construct the AI tool, which was tested in 203 independent MRI data sets. Next, the AI tool was compared against eight qualified radiation oncologists in a multicenter evaluation by using a random sample of 20 test MRI examinations. The Wilcoxon matched-pairs signed rank test was used to compare the difference of Dice similarity coefficient (DSC) of pre- versus post-AI assistance. Results The AI-generated contours demonstrated a high level of accuracy when compared with ground truth contours at testing in 203 patients (DSC, 0.79; 2.0-mm difference in average surface distance). In multicenter evaluation, AI assistance improved contouring accuracy (five of eight oncologists had a higher median DSC after AI assistance; average median DSC, 0.74 vs 0.78; P < .001), reduced intra- and interobserver variation (by 36.4% and 54.5%, respectively), and reduced contouring time (by 39.4%). Conclusion The AI contouring tool improved primary gross tumor contouring accuracy of nasopharyngeal carcinoma, which could have a positive impact on tumor control and patient survival. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Chang in this issue.

A new double photosystems-based ‘Z-scheme’ photoelectrochemical (PEC) sensing platform is designed for ultrasensitive detection of prostate-specific antigen (PSA) by coupling with a three-dimensional (3D) DNA walker. Two photosystems consist of CdS quantum dots (photosystem I; PS I) and BiVO4 photoactive materials (photosystem II; PS II), whereas gold nanoparticles (AuNPs) photodeposited on high-active {010} facets of BiVO4 are used as the electron mediators to promote electron transfer from conduction band of PS II to valence band of PS I. 3D DNA walker-based amplification strategy is carried out between hairpin DNA1 conjugated onto the AuNP, hairpin DNA2 labeled with CdS quantum dot (QD-H2), and DNA walker complementary with the PSA aptamer modified to a magnetic bead (Apt-MB). Upon addition of target, DNA walker strand is displaced from DNA walker/Apt-MB to open hairpin DNA1 on AuNP@BiVO4. In the presence of QD-H2, DNA walker induces the hybridization of DNA1 with DNA2 on the gold nanoparticles step by step, thereby resulting in the assembly of CdS QDs on the AuNP@BiVO4 to form Z-scheme double photosystems with strong photocurrent. Under optimum conditions, the Z-scheme PEC sensing system exhibits good photocurrent responses toward target PSA within the working range of 0.01–50 ng mL–1 at a low detection limit of 1.5 pg mL–1. Good reproducibility and accuracy are acquired for analysis of target PSA and human serum specimens relative to the commercial PSA ELISA kit. Importantly, our strategy provides a new horizon for photoelectrochemical in vitro diagnostics.

Abstract Purpose: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies. Patients and Methods: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR12 weeks). Results: A total of 166 patients were included in the final analysis. Overall, the PFR12 weeks was 68%, and objective response rate was 13% (95% confidence interval, 7.6%–18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR12 weeks, median PFS and OS were: 58%, 4.1 and 11 months for UPS (n = 19); 63%, 5.6 and 13 months for LPS (n = 13); 75%, 11 and 15 months for LMS (n = 26); 75%, 7.7 and 12 months for SS (n = 47); 81%, 5.6 and 12 months for FS (n = 18); 77%, 21 and not reached for ASPS (n = 13); 54%, 11 and 16 months for CCS (n = 7); and 44%, 2.8 and 8.8 months for other sarcoma (n = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred. Conclusions: Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. Clin Cancer Res; 24(21); 5233–8. ©2018 AACR.

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

PURPOSE: The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro. METHODS: The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry. RESULTS: The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line. CONCLUSION: The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) has raised world concern for global epidemic since December, 2019. Limited data are available for liver function in COVID-19 patients. We aimed to investigate the risk factors related to liver injury in the COVID-19 patients. METHODS: A retrospective study was performed in non-ICU Ward at Jinyintan Hospital from February 2, 2020 to February 23, 2020. Consecutively confirmed COVID-19 discharged cases were enrolled. The clinical characteristics of patients with liver injury and without liver injury were compared. RESULTS: A total of 79 COVID-19 patients were included. 31.6%, 35.4% and 5.1% COVID-19 patients had elevated levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and bilirubin respectively. Median value of ALT, AST and bilirubin for entire cohort was 36.5 (17.5 ~ 71.5) U/L, 34.5 (25.3 ~ 55.3) U/L and 12.7 (8.1 ~ 15.4) mmol/L respectively. There were no significant differences in age, previous medical history and symptoms between the two groups. Males were more likely to have liver injury when infected with COVID-19 (P < .05); compared with patients without liver injury, patients with liver injury had increased levels of white blood cell counts, neutrophils, CRP and CT score (P < .05) and had a longer length of stay (P < .05). Logistic regression analyses suggested that the extent of pulmonary lesions on CT was a predictor of liver function damage (P < .05). CONCLUSIONS: Liver injury is common in non-ICU hospitalized COVID-19 patients. It may be related to systemic inflammation. Intense monitoring and evaluation of liver function in patients with severe pulmonary imaging lesions should be considered.

Background: Neurological disorders are a major and increasing global health challenge, which accounts for a substantial portion of the disease burden worldwide. The aim of this systematic analysis is to present the most comprehensive and up-to-date estimates of disease burden, epidemiological trends, and attributable risk factors of neurological disorders at global, regional, and national levels. Methods: We extracted data of 18 neurological disorders from the Global Burden of Disease 2019 study database. The burden of neurological disorders was measured using the incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and further described according to age, sex, year, geographical location and socio-demographic Index (SDI). All estimates were presented with corresponding 95% uncertainty intervals (UIs). Findings: Globally, in 2019, there were nearly 10 million deaths and 349 million DALYs due to neurological disorders. Among the 18 neurological disorders, stroke was the biggest contributor to DALYs (143232.18 [95%UI 133095.81-153241.82] in thousands) and deaths (6552.72 [95%UI 5995.20-7015.14] in thousands), followed by neonatal encephalopathy due to birth asphyxia and trauma. From 1990 to 2019, the DALYs of neurological diseases belonging to the communicable, maternal, neonatal and nutritional categories showed a sharp decrease, while Alzheimer's disease and other dementias and Parkinson's disease showed a large increase. Neurological disorders exhibited different profiles in different regions and age groups. A significant correlation between the SDI and the age-standardized DALY rates was also found except for Alzheimer's disease and other dementias. In addition, risk factors such as high systolic blood pressure, low birth weight and short gestation period, and metabolic risk contribute significantly to neurological disorders. Interpretation: The overall burden of neurological disorders has increased from 1990 to 2019, especially for non-communicable neurological disorders. The substantial variations of burden across regions emphasize the need for region-specific interventional strategies and allocation of resources based on priorities.