Shandong Provincial Hospital

BACKGROUND: Antiplatelet agents are the mainstay for secondary prevention of non-cardioembolic stroke. This systematic review examined the safety and efficacy of short-, middle-, and long-term aspirin in combination with clopidogrel as secondary prevention of stroke or transient ischemic attack (TIA) of presumed arterial origin. METHODS: PubMed, EmBase, and CENTRAL were searched up to May 2014. Randomized controlled trials (RCTs) that compared aspirin plus clopidogrel versus aspirin or clopidogrel as secondary prevention of stroke or TIA of arterial origin were included. The analyses were stratified into short-term (≤3 months), middle-term (>3 months and <1 year), and long-term (≥1 year). Outcomes were compared using risk ratio (RR) and 95% confidence interval (95% CI). RESULTS: Eight RCTs (20,728 patients) were included in the overall analysis. Compared with aspirin or clopidogrel alone, the complete analysis of all the data indicated that the combination therapy significantly reduced the risk of stroke recurrence (RR, 0.82; 95% CI 0.70-0.96, p = 0.01) and major vascular events (RR, 0.84; 95% CI 0.73-0.96, p < 0.01). But the risk of hemorrhagic stroke (RR, 1.59; 95% CI 1.08-2.33, p = 0.02) and major bleeding (RR, 1.83; 95% CI 1.37-2.45, p < 0.01) was increased. No RCT studied middle-term combination therapy. The analyses were therefore stratified into only two subgroups, short- and long-term treatment. Stratified analysis of short-term treatment showed that relative to monotherapy, the drug combination reduced the risk of stroke recurrence (RR, 0.69; 95% CI 0.59-0.81, p < 0.01) and did not increase the risk of hemorrhagic stroke (RR, 1.23; 95% CI 0.50-3.04, p = 0.65) and major bleeding events (RR, 2.17; 95% CI 0.18-25.71, p = 0.54). Short-term combination therapy was associated with a significantly lower risk of major vascular events (RR, 0.70; 95% CI 0.69 to 0.82, p < 0.01). Stratified analysis of long-term treatment revealed that the combination treatment did not decrease the risk of stroke recurrence (RR, 0.92; 95% CI 0.83-1.03, p = 0.15), but was associated with a significantly higher risk of hemorrhagic stroke (RR, 1.67; 95% CI 1.10-2.56, p = 0.02) and major bleeding events (RR, 1.90; 95% CI 1.46-2.48, p < 0.01). Long-term combination therapy failed to reduce the risk of major vascular events (RR, 0.92; 95% CI 0.84-1.03, p = 0.09). CONCLUSIONS: Compared with monotherapy, short-term aspirin in combination with clopidogrel is more effective as secondary prevention of stroke or TIA without increasing the risk of hemorrhagic stroke and major bleeding events. Long-term combination therapy does not reduce the risk of stroke recurrence, and is associated with increased major bleeding events. The clinical applicability of the findings of this systematic review, however, needs to be confirmed in future clinical trials.

OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

BACKGROUND: China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS: For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS: Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION: Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING: Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning.

Abstract Objective To assess the prevalence of diabetes and its risk factors. Design Population based, cross sectional study. Setting 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017. Participants 75 880 participants aged 18 and older—a nationally representative sample of the mainland Chinese population. Main outcome measures Prevalence of diabetes among adults living in China, and the prevalence by sex, regions, and ethnic groups, estimated by the 2018 American Diabetes Association (ADA) and the World Health Organization diagnostic criteria. Demographic characteristics, lifestyle, and history of disease were recorded by participants on a questionnaire. Anthropometric and clinical assessments were made of serum concentrations of fasting plasma glucose (one measurement), two hour plasma glucose, and glycated haemoglobin (HbA 1c ). Results The weighted prevalence of total diabetes (n=9772), self-reported diabetes (n=4464), newly diagnosed diabetes (n=5308), and prediabetes (n=27 230) diagnosed by the ADA criteria were 12.8% (95% confidence interval 12.0% to 13.6%), 6.0% (5.4% to 6.7%), 6.8% (6.1% to 7.4%), and 35.2% (33.5% to 37.0%), respectively, among adults living in China. The weighted prevalence of total diabetes was higher among adults aged 50 and older and among men. The prevalence of total diabetes in 31 provinces ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia. Han ethnicity had the highest prevalence of diabetes (12.8%) and Hui ethnicity had the lowest (6.3%) among five investigated ethnicities. The weighted prevalence of total diabetes (n=8385) using the WHO criteria was 11.2% (95% confidence interval 10.5% to 11.9%). Conclusion The prevalence of diabetes has increased slightly from 2007 to 2017 among adults living in China. The findings indicate that diabetes is an important public health problem in China.

OBJECTIVE: To examine and quantify the potential dose-response relation between fruit and vegetable consumption and risk of all cause, cardiovascular, and cancer mortality. DATA SOURCES: Medline, Embase, and the Cochrane library searched up to 30 August 2013 without language restrictions. Reference lists of retrieved articles. STUDY SELECTION: Prospective cohort studies that reported risk estimates for all cause, cardiovascular, and cancer mortality by levels of fruit and vegetable consumption. DATA SYNTHESIS: Random effects models were used to calculate pooled hazard ratios and 95% confidence intervals and to incorporate variation between studies. The linear and non-linear dose-response relations were evaluated with data from categories of fruit and vegetable consumption in each study. RESULTS: Sixteen prospective cohort studies were eligible in this meta-analysis. During follow-up periods ranging from 4.6 to 26 years there were 56,423 deaths (11,512 from cardiovascular disease and 16,817 from cancer) among 833,234 participants. Higher consumption of fruit and vegetables was significantly associated with a lower risk of all cause mortality. Pooled hazard ratios of all cause mortality were 0.95 (95% confidence interval 0.92 to 0.98) for an increment of one serving a day of fruit and vegetables (P=0.001), 0.94 (0.90 to 0.98) for fruit (P=0.002), and 0.95 (0.92 to 0.99) for vegetables (P=0.006). There was a threshold around five servings of fruit and vegetables a day, after which the risk of all cause mortality did not reduce further. A significant inverse association was observed for cardiovascular mortality (hazard ratio for each additional serving a day of fruit and vegetables 0.96, 95% confidence interval 0.92 to 0.99), while higher consumption of fruit and vegetables was not appreciably associated with risk of cancer mortality. CONCLUSIONS: This meta-analysis provides further evidence that a higher consumption of fruit and vegetables is associated with a lower risk of all cause mortality, particularly cardiovascular mortality.

The aberrant Wnt/β-catenin signaling pathway facilitates cancer stem cell renewal, cell proliferation and differentiation, thus exerting crucial roles in tumorigenesis and therapy response. Accumulated investigations highlight the therapeutic potential of agents targeting Wnt/β-catenin signaling in cancer. Wnt ligand/ receptor interface, β-catenin destruction complex and TCF/β-catenin transcription complex are key components of the cascade and have been targeted with interventions in preclinical and clinical evaluations. This scoping review aims at outlining the latest progress on the current approaches and perspectives of Wnt/β-catenin signaling pathway targeted therapy in various cancer types. Better understanding of the updates on the inhibitors, antagonists and activators of Wnt/β-catenin pathway rationalizes innovative strategies for personalized cancer treatment. Further investigations are warranted to confirm precise and secure targeted agents and achieve optimal use with clinical benefits in malignant diseases.

The prognostic value of FoxP3(+) regulatory T cells (Tregs) in cancer remains controversial. We did a meta-analysis to assess the prognostic effect of FoxP3(+) Treg across different types of cancer and to investigate factors associated with variations in this effect. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched to identify eligible studies. In total, we analyzed 76 articles encompassing 17 types of cancer, and including 15,512 cancer cases. The overall pooled analysis including all types of cancer suggested FoxP3(+)Tregs had a significant negative effect on overall survival (OS) (OR 1.46, P < 0.001), but the prognostic effect varied greatly according to tumor site. High FoxP3(+) Tregs infiltration was significantly associated with shorter OS in the majority of solid tumors studied, including cervical, renal, melanomas, and breast cancers, et al; whereas, FoxP3(+) Tregs were associated with improved survival in colorectal, head and neck, and oesophageal cancers. The stratified analysis suggested the molecular subtype and tumor stage significantly influenced the prognostic value of FoxP3(+) Tregs in certain types of cancer. In conclusion, our meta-analysis suggests that the prognostic role of FoxP3(+) Tregs was highly influenced by tumor site, and was also correlated with the molecular subtype and tumor stage.

BACKGROUND: The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome. METHODS: In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer. RESULTS: Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06). CONCLUSIONS: Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).

Coronavirus disease 2019 (COVID-19) has become a pandemic, but its reported characteristics and outcomes vary greatly amongst studies. We determined pooled estimates for clinical characteristics and outcomes in COVID-19 patients including subgroups by disease severity (based on World Health Organization Interim Guidance Report or Infectious Disease Society of America/American Thoracic Society criteria) and by country/region. We searched Pubmed, Embase, Scopus, Cochrane, Chinese Medical Journal, and preprint databases from 1 January 2020 to 6 April 2020. Studies of laboratory-confirmed COVID-19 patients with relevant data were included. Two reviewers independently performed study selection and data extraction. From 6007 articles, 212 studies from 11 countries/regions involving 281 461 individuals were analyzed. Overall, mean age was 46.7 years, 51.8% were male, 22.9% had severe disease, and mortality was 5.6%. Underlying immunosuppression, diabetes, and malignancy were most strongly associated with severe COVID-19 (coefficient = 53.9, 23.4, 23.4, respectively, all P < .0007), while older age, male gender, diabetes, and hypertension were also associated with higher mortality (coefficient = 0.05 per year, 5.1, 8.2, 6.99, respectively; P = .006-.0002). Gastrointestinal (nausea, vomiting, abdominal pain) and respiratory symptoms (shortness of breath, chest pain) were associated with severe COVID-19, while pneumonia and end-organ failure were associated with mortality. COVID-19 is associated with a severe disease course in about 23% and mortality in about 6% of infected persons. Individuals with comorbidities and clinical features associated with severity should be monitored closely, and preventive efforts should especially target those with diabetes, malignancy, and immunosuppression.

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

BACKGROUND: Primary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in elucidating the genetics of POI. METHODS: A search for original articles published up to May 2015 was performed using PubMed and Google Scholar, identifying studies on the genetic etiology of POI. Studies were included if chromosomal analysis, candidate gene screening and a genome-wide study were conducted. Articles identified were restricted to English language full-text papers. RESULTS: Chromosomal abnormalities have long been recognized as a frequent cause of POI, with a currently estimated prevalence of 10-13%. Using the traditional karyotype methodology, monosomy X, mosaicism, X chromosome deletions and rearrangements, X-autosome translocations, and isochromosomes have been detected. Based on candidate gene studies, single gene perturbations unequivocally having a deleterious effect in at least one population include Bone morphogenetic protein 15 (BMP15), Progesterone receptor membrane component 1 (PGRMC1), and Fragile X mental retardation 1 (FMR1) premutation on the X chromosome; Growth differentiation factor 9 (GDF9), Folliculogenesis specific bHLH transcription factor (FIGLA), Newborn ovary homeobox gene (NOBOX), Nuclear receptor subfamily 5, group A, member 1 (NR5A1) and Nanos homolog 3 (NANOS3) seem likely as well, but mostly being found in no more than 1-2% of a single population studied. Whole genome approaches have utilized genome-wide association studies (GWAS) to reveal loci not predicted on the basis of a candidate gene, but it remains difficult to locate causative genes and susceptible loci were not always replicated. Cytogenomic methods (array CGH) have identified other regions of interest but studies have not shown consistent results, the resolution of arrays has varied and replication is uncommon. Whole-exome sequencing in non-syndromic POI kindreds has only recently begun, revealing mutations in the Stromal antigen 3 (STAG3), Synaptonemal complex central element 1 (SYCE1), minichromosome maintenance complex component 8 and 9 (MCM8, MCM9) and ATP-dependent DNA helicase homolog (HFM1) genes. Given the slow progress in candidate-gene analysis and relatively small sample sizes available for GWAS, family-based whole exome and whole genome sequencing appear to be the most promising approaches for detecting potential genes responsible for POI. CONCLUSION: Taken together, the cytogenetic, cytogenomic (array CGH) and exome sequencing approaches have revealed a genetic causation in ∼20-25% of POI cases. Uncovering the remainder of the causative genes will be facilitated not only by whole genome approaches involving larger cohorts in multiple populations but also incorporating environmental exposures and exploring signaling pathways in intragenic and intergenic regions that point to perturbations in regulatory genes and networks.

Abstract Purpose: The third-generation EGFR tyrosine kinase inhibitor osimertinib is approved to treat patients with EGFR T790M-positive non–small cell lung cancer (NSCLC) who have developed resistance to earlier-generation drugs. Acquired EGFR C797S mutation has been reported to mediate osimertinib resistance in some patients. However, the remaining resistance mechanisms are largely unknown. Experimental Design: We performed mutation profiling using targeted next-generation sequencing (NGS) for 416 cancer-relevant genes on 93 osimertinib-resistant lung cancer patients' samples, mainly cell-free DNAs (cfDNAs), and matched pretreatment samples of 12 patients. In vitro experiments were conducted to functionally study the secondary EGFR mutations identified. Results: EGFR G796/C797, L792, and L718/G719 mutations were identified in 24.7%, 10.8%, and 9.7% of the cases, respectively, with certain mutations coexisting in one patient with different prevalence. L792 and L718 mutants markedly increased the half inhibitory concentration (IC50) of osimertinib in vitro, among which the L718Q mutation conferred the greatest resistance to osimertinib, as well as gefitinib resistance when not coexisting with T790M. Further analysis of the 12 matched pretreatment samples confirmed that these EGFR mutations were acquired during osimertinib treatment. Alterations in parallel or downstream oncogenes such as MET, KRAS, and PIK3CA were also discovered, potentially contributing to the osimertinib-resistance in patients without EGFR secondary mutations. Conclusions: We present comprehensive mutation profiles of a large cohort of osimertinib-resistance lung cancer patients using mainly cfDNA. Besides C797 mutations, novel secondary mutations of EGFR L718 and L792 residues confer osimertinib resistance, both in vitro and in vivo, and are of great clinical and pharmaceutical relevance. Clin Cancer Res; 24(13); 3097–107. ©2018 AACR.

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

Recent studies indicate that Traditional Chinese medicine (TCM) can play an important role in the whole course of cancer treatment such as recovery stages of post-operative, radiotherapy or chemotherapy stages instead of only terminal stage of cancer. In this review, we have summarized current evidence for using TCM as adjuvant cancer treatment in different stages of cancer lesions. Some TCMs (e.g., TJ-41, Liu-jun-zi-tang, PHY906, Coumarin, and Aescine) are capable of improving the post-operative symptoms such as fatigue, pain, appetite, diarrhea, nausea, vomiting, and lymphedema. Some TCMs (e.g., Ginseng, Huang-Qi, BanZhiLian, TJ-48, Huachansu injection, Shenqi fuzheng injection, and Kanglaite injection) in combination with chemo- or radio-therapy are capable of enhancing the efficacy of and diminishing the side effects and complications caused by chemo- and radiotherapy. Taken together, they have great advantages in terms of suppressing tumor progression, relieving surgery complications, increasing the sensitivity of chemo- and radio- therapeutics, improving an organism's immune system function, and lessening the damage caused by surgery, chemo- or radio-therapeutics. They have significant effects on relieving breast cancer-related lymphedema, reducing cancer-related fatigue and pain, improving radiation pneumonitis and gastrointestinal side effects, protecting liver function, and even ameliorating bone marrow suppression. This review of those medicines should contribute to an understanding of Chinese herbal medicines as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer, by providing useful information for development of more effective anti-cancer drugs and making more patients "survival with cancer" for a long time.

Metabolic reprogramming is reported to be one of the hallmarks of cancer, which is an adaptive mechanism by which fast-growing cancer cells adapt to their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Meanwhile, the TME is a highly heterogeneous ecosystem incorporating cancer cells, fibroblasts, adipocytes, endothelial cells, mesenchymal stem cells, and extracellular matrix. Accumulated evidence indicates that exosomes may transfer biologically functional molecules to the recipient cells, which facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells and their surrounding stromal cells. In this review, we present the role of exosomes in the TME and the underlying mechanism of how exosomes exacerbate tumor development through metabolic reprogramming. In addition, we will also discuss the potential role of exosomes targeting metabolic process as biomarkers for tumor diagnosis and prognosis, and exosomes-mediated metabolic reprogramming as potential targets for cancer therapy. Furthermore, a better understanding of the link between exosomes and metabolic reprogramming, and their impact on cancer progression, would provide novel insights for cancer prevention and treatment in the future.

OBJECTIVE: To assess the current prevalence of and risk factors for infertility among couples of reproductive age in China. DESIGN: Population-based cross-sectional study. SETTING: We approached 25 270 couples in eight provinces/municipalities, of whom 18 571 (response rate 74%) were interviewed. POPULATION: Couples living together and married for more than 1 year, of whom the female spouse was 20-49 years old. METHODS: Women were approached via telephone and face-to-face conversation to complete the standardised and structured questionnaire by trained interviewers. MAIN OUTCOME MEASURES: Prevalence of and risk factors for infertility. RESULTS: Among women 'at risk' of pregnancy, the prevalence of infertility was 15.5% (2680/17 275). Among 10 742 women attempting to become pregnant, the prevalence of infertility was 25.0% (2680/10 742), which increased with age in the second population. Among women who failed to achieve pregnancy in the last 12 months, 3470 finished our questionnaire about fertility care, and 55.2% (1915/3470) of them had sought medical help. Sociodemographic risk factors for infertility included lower educational level [adjusted odds ratio (aOR) 3.4, 95% CI 2.0-5.5] and employment (aOR 2.3, 95% CI 1.9-2.9). Clinical risk factors were irregular menstrual cycle (aOR 1.8, 95% CI 1.2-2.5), light menstrual blood volume (aOR 1.6, 95% CI 1.2-2.0), history of cervicitis (aOR 1.5, 95% CI 1.2-2.0) and endometriosis (aOR 3.1, 95% CI 1.1-9.3), previous stillbirth (aOR 2.1, 95% CI 1.3-3.3) and miscarriage (aOR 2.7, 95% CI 2.1-3.5). In addition, history of operation was a significant risk factor of infertility. CONCLUSIONS: Among couples of reproductive age in China, the prevalence of infertility was 25%, and almost half of the couples experiencing infertility had not sought medical help. TWEETABLE ABSTRACT: In China, 25% of couples actively attempting to become pregnant suffered infertility.

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) and osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis and function is important. Mitophagy, a process that selectively clears damaged or dysfunctional mitochondria through autophagic machinery, functions to maintain mitochondrial quality control and homeostasis. IVDD and OA are similar joint diseases involving the degradation of cartilaginous tissues that are mainly caused by oxidative stress, cell apoptosis and extracellular matrix (ECM) degradation. Over the past decade, accumulating evidence indicates the essential role of mitophagy in the pathogenesis of IVDD and OA. Importantly, strategies by the regulation of mitophagy exert beneficial effects in the pre-clinical experiments. Given the importance and novelty of mitophagy, we provide an overview of mitophagy pathways and discuss the roles of mitophagy in IVDD and OA. We also highlight the potential of targeting mitophagy for the treatment of degenerative joint diseases.Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy and beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CDH6: cadherin 6; CEP: cartilaginous endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: extracellular matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin 1 beta; IMM: inner mitochondrial membranes; IVDD: intervertebral disc degeneration; MAPK8/JNK: mitogen-activated protein kinase 8; MFN1: mitofusin 1; MFN2: mitofusin 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: mitochondrial transmembrane potential; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; NFE2L2: nuclear factor: erythroid 2 like 2; NP: nucleus pulposus; OA: osteoarthritis; OPA1: OPA1: mitochondrial dynamin like GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin protein ligase; PD: Parkinson disease; PGAM5: PGAM family member 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator 1 alpha; PHF23: PHD finger protein 23; PINK1: PTEN induced putative kinase 1; ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin 1; SIRT2: sirtuin 2; SIRT3: sirtuin 3; SQSTM1/p62: sequestosome 1; TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel.

Although the innate immune response to induce postischemic inflammation is considered as an essential step in the progression of cerebral ischemia injury, the role of innate immunity mediator NLRP3 in the pathogenesis of ischemic stroke is unknown. In this study, focal ischemia was induced by middle cerebral artery occlusion in NLRP3(-/-), NOX2(-/-), or wild-type (WT) mice. By magnetic resonance imaging (MRI), Evans blue permeability, and electron microscopic analyses, we found that NLRP3 deficiency ameliorated cerebral injury in mice after ischemic stroke by reducing infarcts and blood-brain barrier (BBB) damage. We further showed that the contribution of NLRP3 to neurovascular damage was associated with an autocrine/paracrine pattern of NLRP3-mediated interleukin-1β (IL-1β) release as evidenced by increased brain microvessel endothelial cell permeability and microglia-mediated neurotoxicity. Finally, we found that NOX2 deficiency improved outcomes after ischemic stroke by mediating NLRP3 signaling. This study for the first time shows the contribution of NLRP3 to neurovascular damage and provides direct evidence that NLRP3 as an important target molecule links NOX2-mediated oxidative stress to neurovascular damage in ischemic stroke. Pharmacological targeting of NLRP3-mediated inflammatory response at multiple levels may help design a new approach to develop therapeutic strategies for prevention of deterioration of cerebral function and for the treatment of stroke.

OBJECTIVE: To update the prevalence of eating disorders in the general population before 2021 and to analyze the distribution characteristics at different times and in different regions and sexes, as well as the diagnostic criteria. METHODS: Based on the method from a previous report by the authors, studies were identified from the following databases: PubMed/Medline, PsycINFO, ISI Web of Knowledge, Ovid and the 4 most important Chinese databases. Articles in English and Chinese before 2021 were retrieved. The data retrieved at this time were pooled with the data from a previous report for analyses. RESULTS: Thirty-three studies were identified, which included 18 studies supplemented in this retrieval. The pooled lifetime and 12-month prevalence of eating disorders were 0.91% (95% CI, 0.48-1.71) and 0.43% (95% CI, 0.18-0.78), respectively. The pooled lifetime and 12-month prevalence of the subgroup EDs (any), which covers all types of eating disorders, were 1.69% and 0.72%, respectively. The lifetime prevalence of AN, BN and BED was 0.16% (95% CI, 0.06-0.31), 0.63% (95% CI, 0.33-1.02) and 1.53% (95% CI, 1.00-2.17), respectively. The lifetime prevalence of EDs in Western countries was 1.89%, and was high at 2.58% in females. Prevalence studies using DSM-5 criteria were scarce. CONCLUSIONS: The prevalence of eating disorders might be underestimated thus far. Not all types of EDs were included in a majority of epidemiological surveys, and the prevalence rates of the new types of EDs were significantly higher. Eating disorders were especially common in Western countries and in females. New diagnostic criteria should be used to comprehensively assess all types of eating disorders. LEVEL OF EVIDENCE: 1, systematic review and meta-analysis.

OBJECTIVE: To examine and quantify the potential dose-response relationship between red and processed meat consumption and risk of all-cause, cardiovascular and cancer mortality. DESIGN: We searched MEDLINE, Embase, ISI Web of Knowledge, CINHAL, Scopus, the Cochrane library and reference lists of retrieved articles up to 30 November 2014 without language restrictions. We retrieved prospective cohort studies that reported risk estimates for all-cause, cardiovascular and cancer mortality by red and/or processed meat intake levels. The dose-response relationships were estimated using data from red and processed meat intake categories in each study. Random-effects models were used to calculate pooled relative risks and 95 % confidence intervals and to incorporate between-study variations. RESULTS: Nine articles with seventeen prospective cohorts were eligible in this meta-analysis, including a total of 150 328 deaths. There was evidence of a non-linear association between processed meat consumption and risk of all-cause and cardiovascular mortality, but not for cancer mortality. For processed meat, the pooled relative risk with an increase of one serving per day was 1·15 (95 % CI 1·11, 1·19) for all-cause mortality (five studies; P<0·001 for linear trend), 1·15 (95 % CI 1·07, 1·24) for cardiovascular mortality (six studies; P<0·001) and 1·08 (95 % CI 1·06, 1·11) for cancer mortality (five studies; P<0·001). Similar associations were found with total meat intake. The association between unprocessed red meat consumption and mortality risk was found in the US populations, but not in European or Asian populations. CONCLUSIONS: The present meta-analysis indicates that higher consumption of total red meat and processed meat is associated with an increased risk of total, cardiovascular and cancer mortality.