Sixth Affiliated Hospital of Kunming Medical University

The association between abdominal obesity (as measured by waist circumference (WC) and waist-to-hip ratio (WHR)) and colorectal cancer (CRC) has not been fully quantified, and the magnitude of CRC risk associated with abdominal obesity is still unclear. A meta-analysis of prospective studies was performed to elucidate the CRC risk associated with abdominal obesity. Pubmed and Embase were searched for studies assessing the association between abdominal obesity and CRC risk. Relative risks (RRs) with 95% confidence intervals (95% CIs) were pooled using random-effects model of meta-analysis. Nineteen prospective cohort studies from eighteen publications were included in this meta-analysis. A total of 12,837 CRC cases were identified among 1,343,560 participants. Greater WC and WHR were significantly associated with increased risk of total colorectal cancer (WC: RR 1.42, 95% CI 1.30, 1.55; WHR: RR 1.39, 95% CI 1.25, 1.53), colon cancer (WC: RR 1.53, 95% CI 1.36, 1.72; WHR: 1.39, 95% CI 1.18, 1.63), and rectal cancer (WC: RR 1.20, 95% CI 1.03, 1.39; WHR: RR 1.22, 95% CI 1.05, 1.42). Subgroup analyses further identified the robustness of the association above. No obvious risk of publication bias was observed. In summary, abdominal obesity may play an important role in the development of CRC.

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).

OBJECTIVES: This study aimed to investigate the dynamic trends in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels with ageing. DESIGN: A Chinese population-based cross-sectional study. SETTING: A physical examination centre of a general hospital. PARTICIPANTS: Adult subjects (178 167: 103 461 men and 74 706 women) without a known medical history or treatments that affect lipid metabolism. MAIN OUTCOME MEASURES: Dynamic trends in the above-mentioned lipid parameters with ageing were explored; turning points of age were established using age stratification and validated by fitted multivariate linear regression modelling. RESULTS: Age was found to be an independent factor extensively associated with lipid levels in both sexes when adjusted for serum glucose, body mass index, lifestyle, drinking and smoking. Age was positively associated with TC, logarithm-transformed TG (LnTG) and LDL-C levels in men ≤40, ≤40 and ≤60 years old (yo) and in women ≤60, ≤70 and ≤60 yo, respectively. Conversely, age correlated negatively with TC, LnTG and LDL-C levels in men ≥61, ≥41 and ≥61 yo and in women ≥61, ≥71 and ≥61 yo, respectively. TC, TG and LDL-C levels in women were initially lower than those in men but surpassed those in men in 51-55, 61-65 and 51-55 yo age groups. The trends in HDL-C levels with age were relatively irregular, although HDL-C levels in women were higher than in men for all age groups. CONCLUSIONS: The definition of dyslipidaemia, the atherosclerotic cardiovascular disease risk assessment and the initiation/goals of statin therapy should fully consider age-related trends in lipid levels and sex differences.

OBJECTIVE: This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC) by conducting a meta-analysis of 10 cohort studies. METHODS: The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed. RESULTS: The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS), nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR) 1.22; 95% confidence interval (CI) 1.08-1.38). In addition, we also found a promising increased risk for colon cancer (CC) (RR 1.30, 95% CI 1.07-1.58), but no relationship between cholecystectomy and rectum cancer (RC) (RR 1.09; 95% CI 0.89-1.34) was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC) was found (RR 1.18, 95% CI 1.11-1.26). After combining the ACC, transverse colon cancer (TCC), sigmoid colon cancer (SCC) and descending colon cancer (DCC) patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11-1.26). Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11-1.26) in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05-1.36). Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03-1.34). However, there was no relationship between gender and CC or RC. Furthermore, no publication bias was observed, and the sensitivity analysis indicated stable results. CONCLUSIONS: This meta-analysis of 10 cohort studies revealed that cholecystectomy is associated with an increased risk for CRC, CC and ACC, particularly in Western countries. No relationship between cholecystectomy and RC was observed. There was no relationship between gender and either CC or RC, but a positive relationship between female gender and CRC was observed.

Lipotoxicity is the dysregulation of the lipid environment and/or intracellular composition that leads to accumulation of harmful lipids and ultimately to organelle dysfunction, abnormal activation of intracellular signaling pathways, chronic inflammation and cell death. It plays an important role in the development of acute kidney injury and chronic kidney disease, including diabetic nephropathy, obesity-related glomerulopathy, age-related kidney disease, polycystic kidney disease, and the like. However, the mechanisms of lipid overload and kidney injury remain poorly understood. Herein, we discuss two pivotal aspects of lipotoxic kidney injury. First, we analyzed the mechanism of lipid accumulation in the kidney. Accumulating data indicate that the mechanisms of lipid overload in different kidney diseases are inconsistent. Second, we summarize the multiple mechanisms by which lipotoxic species affect the kidney cell behavior, including oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, dysregulated autophagy, and inflammation, highlighting the central role of oxidative stress. Blocking the molecular pathways of lipid accumulation in the kidney and the damage of the kidney by lipid overload may be potential therapeutic targets for kidney disease, and antioxidant drugs may play a pivotal role in the treatment of kidney disease in the future.

Objective To accurately estimate the global prevalence of non-tuberculous mycobacteria (NTM) in adults with non-cystic fibrosis (non-CF) bronchiectasis and to determine the proportion of NTM species and subspecies in clinical patients from 2006 to 2021. Design Systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources Medline, Embase, Cochrane Library and Web of Science were searched for articles published between 2006 and 2021. Eligibility criteria for selecting studies We included all the prospective or retrospective studies without language restrictions and all patients were adults (≥18 years of age) with non-CF bronchiectasis. The studies estimated the effect size of the prevalence of NTM with a sample size ≥40, and patients were registered in and after 2006. Data extraction and synthesis Two reviewers screened the titles, abstracts and full texts independently. Relevant information was extracted and curated into tables. Risk of bias was evaluated following the Cochrane Collaboration’s tool. Meta-analysis was performed with software R Statistics V.3.6.3 using random effect model with 95% CI. I 2 index and Q statistics were calculated to assess the heterogeneity, and mixed-effects meta-regression analyses were performed to identify the sources of heterogeneity. The proportions of NTM subspecies were examined using Shapiro-Wilk normality test in R. Results Of all the 2014 studies yielded, 24 met the inclusion criteria. Of these, 14 were identified to be randomised controlled studies and included for an accurate estimation. The global prevalence of NTM in adults with non-CF bronchiectasis from 2006 to 2021 was estimated to be approximately 10%, with great variations primarily due to geographical location. Mycobacterium avium complex was the most common subspecies, followed by Mycobacterium simiae and Mycobacterium gordonae . Conclusions The prevalence of NTM in adults with non-CF bronchiectasis has been on the rise and the most common subspecies changed greatly in recent years. More cohort studies should be done in many countries and regions for future estimates. PROSPERO registration number CRD42020168473.

OBJECTIVE: ZNF804A is a schizophrenia risk gene that was recently identified by genome-wide association studies as well as subsequent replications. Although the results are consistent among studies in European populations, there have been conflicting reports in Chinese populations. The authors conducted both association and functional analyses to test whether ZNF804A is a risk gene for schizophrenia in Chinese populations. METHOD: The authors recruited two case-control samples of independent Han Chinese (a total of 2,207 participants) from southwestern China. A total of six single-nucleotide polymorphisms (SNPs), including the key SNP (rs1344706) that showed significant association with schizophrenia in European populations and the other five promoter SNPs of ZNF804A, were tested. Based on the results of the association analysis, the authors performed two functional assays to test the impact of the risk SNP on transcriptional factor binding affinity and promoter activity. RESULTS: The SNP rs1344706 was not associated with schizophrenia in either of the two Han Chinese groups, and this result was confirmed by meta-analyses in five Han Chinese samples. However, the authors identified two ZNF804A promoter SNPs that were significantly associated with schizophrenia in both samples, and the significance was strengthened in the combined samples and further supported by haplotype analysis. The functional assays demonstrated that the risk SNP (rs359895) can influence Sp1 binding affinity, resulting in a higher promoter activity of the risk allele. CONCLUSIONS: Our results suggest that ZNF804A is a common risk gene for schizophrenia in world populations and that the newly identified functional SNP (rs359895) is likely a risk SNP for schizophrenia.

BACKGROUND: To analyze and compare the economic outcomes of adjuvant chemotherapy with capecitabine plus oxaliplatin (referred to as the XELOX strategy) and of S-1 (the S-1 strategy) for gastric cancer patients after D2 gastrectomy. METHODS: A Markov model was developed to simulate the lifetime disease course associated with stage II or III gastric cancer after D2 gastrectomy. The lifetime quality-adjusted life years (QALYs), associated costs, and incremental cost-effectiveness ratios (ICERs) were estimated. The clinical data were derived from the results of pilot studies. Direct costs were estimated from the perspective of the Chinese healthcare system, and the utility data were measured from end-point observations of Chinese patients. Sensitivity analyses were used to explore the impact of uncertainty on the model's outcomes. RESULTS: The combined adjuvant chemotherapy strategy with XELOX yielded the greatest increase in QALYs over the course of the disease (8.1 QALYs compared with 7.8 QALYs for the S-1 strategy and 6.2 for surgery alone). The incremental cost per QALY gained using the XELOX strategy was significantly lower than that for the S-1 strategy ($3,502 vs. $6,837, respectively). The results were sensitive to the costs of oxaliplatin and the hazard ratio of relapse-free survival. CONCLUSION: The observations reported herein suggest that adjuvant therapy with capecitabine plus oxaliplatin is a highly cost-effective strategy and more favorable treatment option than the S-1 strategy in patients with stage II or III gastric cancer who have undergone D2 gastrectomy.

BACKGROUND: Melatonin (MT), ubiquitous in almost all organisms, functions as a free radical scavenger. Despite several reports on its role as an antioxidant in animals, plants, and some microorganisms, extensive studies in filamentous fungi are limited. Based upon the role of melatonin as an antioxidant, we investigated its role in heavy metal-induced stress tolerance in Exophiala pisciphila, a dark septate endophyte (DSE), by studying the underlying mechanisms in alleviating oxidative stress and reducing heavy metal accumulation. RESULTS: A significant decrease in malondialdehyde (MDA) and oxygen free radical (OFR) in E. pisciphila was recorded under Cd, Zn, and Pb stresses as compared to the control. Pretreatment of E. pisciphila with 200.0 μM exogenous melatonin significantly increased the activity of superoxide dismutase (SOD) under Zn and Pb stresses. Pretreatment with 200.0 μM melatonin also lowered Cd, Zn, and Pb concentrations significantly. Melatonin production was enhanced by Cd, Cu, and Zn after 2 d, and melatonin biosynthetic enzyme genes, E. pisciphila tryptophan decarboxylase (EpTDC1) and serotonin N-acetyltransferase (EpSNAT1), were transcriptionally upregulated. The overexpression of EpTDC1 and N-acetylserotonin O-methyltransferase (EpASMT1) in Escherichia coli and Arabidopsis thaliana enhanced its heavy metal-induced stress tolerance. The overexpression of EpTDC1 and EpASMT1 reduced the Cd accumulation in the whole A. thaliana plants, especially in the roots. CONCLUSIONS: Melatonin conferred heavy metal-induced stress tolerance by alleviating oxidative stress, activating antioxidant enzyme SOD, and reducing heavy metal accumulation in E. pisciphila. Melatonin biosynthetic enzyme genes of E. pisciphila also played key roles in limiting excessive heavy metal accumulation in A. thaliana. These findings can be extended to understand the role of melatonin in other DSEs associated with economically important plants and help develop new strategies in sustainable agriculture practice where plants can grow in soils contaminated with heavy metals.

Background: COVID-19 first appeared in China in December 2019, with a high rate of infectivity and morbidity, which brought tremendous psychological pressure to healthcare workers. Purpose: To understand the psychological health status of healthcare workers during the COVID-19 outbreak and decline, and to provide a theoretical reference for the future establishment of a psychological crisis intervention system. Methods: Healthcare workers were recruited using convenience sampling and snowball sampling methods, and the electronic version of the SCL-90 scale and a sociodemographic questionnaire were administered. In the pretest, a total of 5018 responses were collected; after six weeks, random sampling was performed. The SCL-90 and measures of other epidemic-related problems were administered, with 1570 responses received; then, the final data analysis was performed. Results: After six weeks, the post-test GSI score; SCL-90 total score; and PST, PSDI, O-C, I-S, DEP, ANX, PHOB, PAR, PSY, and HOS scores were significantly lower than the corresponding pretest scores (p < 0.05). The results by occupational category showed that the scores of nursing staff decreased significantly for 12 indexes and that the scores of the doctors and other hospital staff also significantly decreased. There was a significant difference between the pretest (50.78 ± 28.18) and post-test (45.00 ± 28.49) scores for the degree of worry about the epidemic. Healthcare workers believed that the top three aspects of life affected by the epidemic were economic problems (816 people), interpersonal communication problems (731 people), and mental health (728 people). Conclusion: Over the course of the epidemic, the item scores generally declined significantly. Therefore, during an outbreak period, attention should be paid to psychological crisis interventions for healthcare workers; problems caused by psychological pressure, and even other psychological conditions, can be significantly alleviated to reduce the probability of subsequent health problems.

Secreted frizzled-related protein-1 (SFRP1) is a negative regulatory molecule of the WNT signaling pathway and serves as a therapeutic target for bone formation in osteoporosis. In this study, we first established an ovariectomized (OVX) rat model to simulate postmenopausal osteoporosis and found significant changes in miR-542-3p and sFRP1 expression by RNA sequencing and qRT-PCR. In addition, there was a significant negative correlation between miR-542-3p and sFRP1 mRNA levels in postmenopausal women with osteoporosis. We found that miR-542-3p inhibited the expression of sFRP1 mRNA by luciferase reporter assay. When the miR-542-3p binding site in sFRP1 3'UTR was deleted, it did not affect its expression. Western blot results showed that miR-542-3p inhibited the expression of SFRP1 protein. The expression of SFRP1 was significantly increased in osteoblast-induced mesenchymal stem cells (MSC), whereas the expression of miR-542-3p was significantly decreased. And miR-542-3p transfected MSCs showed a significant increase in osteoblast-specific marker expression, indicating that miR-542-3p is necessary for MSC differentiation. Inhibition of miR-542-3p reduced bone formation, confirmed miR-542-3p play a role in bone formation in vivo. In general, these data suggest that miR-542-3p play an important role in bone formation via inhibiting SFRP1 expression and inducing osteoblast differentiation.

BACKGROUND: Ovarian cancer is the most lethal gynecological malignant cancer in the female genital system. The dysfunction of miRNA contributes to ovarian cancer development. MATERIAL AND METHODS: The miR-1271 level in ovarian cancer tissues and cells was assayed by qRT-PCR. The miR-1271 expression in cells was overexpressed by miRNA-mimic transfection and reduced by miRNA-antisense-oligonucleotide (ASO) transfection. Cell proliferation was analyzed by an MTT assay. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The protein level was assayed by Western blotting. RESULTS: The ovarian cancer tissue and cell lines showed low levels of miR-1271. Low levels of miR-1271 in ovarian cancer tissues were correlated with a low rate of patient survival, and the overexpression of miR-1271 inhibited the proliferation of ovarian cancer cells. The 3' UTR of cyclin G1 (CCNG1) was targeted by miR-1271. CONCLUSIONS: Low levels of miR-1271 in ovarian cancer tissues promoted cancer cell growth. MiR-1271 may be a new predictor of prognosis in ovarian cancer. MiR-1271 exerted its role by targeting CCNG1.

Development of distant metastasis is the main cause of deaths in prostate cancer (PCa) patients. Understanding the mechanism of PCa metastasis is of utmost importance to improve its prognosis. The role of exosomal long noncoding RNA (lncRNA) has been reported not yet fully understood in the metastasis of PCa. Here, we discovered an exosomal lncRNA HOXD-AS1 is upregulated in castration resistant prostate cancer (CRPC) cell line derived exosomes and serum exosomes from metastatic PCa patients, which correlated with its tissue expression. Further investigation confirmed exosomal HOXD-AS1 promotes prostate cancer cell metastasis in vitro and in vivo by inducing metastasis associated phenotype. Mechanistically exosomal HOXD-AS1 was internalized directly by PCa cells, acting as competing endogenous RNA (ceRNA) to modulate the miR-361-5p/FOXM1 axis, therefore promoting PCa metastasis. In addition, we found that serum exosomal HOXD-AS1 was upregulated in metastatic PCa patients, especially those with high volume disease. And it is correlated closely with Gleason Score, distant and nodal metastasis, Prostatic specific antigen (PSA) recurrence free survival, and progression free survival (PFS). This sheds a new insight into the regulation of PCa distant metastasis by exosomal HOXD-AS1 mediated miR-361-5p/FOXM1 axis, and provided a promising liquid biopsy biomarker to guide the detection and treatment of metastatic PCa.

OBJECTIVE: Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan-Meier survival curves. The publication bias was examined by Egger's test. RESULTS: Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542-1.969, P < 0.001) and PFS (HR = 1.385, 95%CI:1.169-1.641, P = 0.003) in the high D-dimer group were significantly lower than those in the low D-dimer group. Subgroup analysis suggested that localization, detection methods and disease stage had an important effect on the prognosis. CONCLUSION: This meta-analysis revealed that the high plasma D-dimer level leads to lower survival than in the low D-dimer level, which might provide an important clue for high plasma D-dimer level as an independent factor of poor prognosis in patients with lung cancer.

OBJECTIVE: The problem of learning burnout of medical students is becoming prominent, and empathy can play a good predictive role in learning burnout. The present study aimed to investigate the relationship between empathy and learning burnout, as well as the mediation effect of resilience in this relation. METHODS: Five hundred and eighty-eighth college students from a key medical university in Yunnan Province was investigated using the Basic Empathy Scale, Learning Burnout Scale, and Connor-Davidson Resilience Scale. All the measures showed good reliability and validity in the present study. Data were analyzed using SPSS 23.0 and Amos 22.0. RESULTS: Using structural equation modeling, we tested a conceptual model indicated that: (1) medical students' empathy negatively and significantly predicted learning burnout; (2) medical students' empathy positively predicts mental resilience; (3) resilience of medical students negatively predicts learning burnout; (4) resilience partially mediated the relationship between empathy and learning burnout of medical students, while also controlling for family socioeconomic status. CONCLUSION: These findings highlight the mediating role of resilience in the effect of empathy on learning burnout of medical college students. It may contribute to a better understanding of the effect of empathy. Moreover, it can also provide constructive suggestions for protecting and improve empathy and resilience of medical college students.

BACKGROUND: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain. METHODS: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90. RESULTS: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups. CONCLUSIONS: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups. TRIAL REGISTRATION: NCT03003559 . Registered on December 28, 2016.

Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting adenylyl cyclase isoform 6 (ADCY6) through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the down-regulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, the present study shows that down-regulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by up-regulating ADCY6, which may represent a novel target for OP treatment.

OBJECTIVE: To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies. METHODS: Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates. RESULTS: Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed. CONCLUSIONS: This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures.

We investigated changes in the susceptibility of Plasmodium falciparum to artesunate in vitro using Rieckmann's microtest in Yunnan Province, China, during the period 1988 to 1999. Longitudinal surveillance studies in 1988, 1992 and 1999 revealed that the IC50s were 6.2, 7.2 and 20.7 nmol/L, respectively and mean concentrations completely inhibiting schizont formation (CIMC) were 37.8, 46.1 and 74.0 nmol/L, respectively. The IC50 and CIMC in 1999 were 3.3 and 2 times greater than in 1988. In cross-sectional tests from 1991 to 1993, the susceptibility of P. falciparum isolates from areas in the western and the southern parts of Yunnan Province were similar, but lower than in the south-eastern and central parts of the province. The results suggest that P. falciparum is generally susceptible to artemisinin derivatives but indicate a reduction in susceptibility during the study period in areas where the drugs have been used for a long time.

The distribution of Yersinia enterocolitica in slaughtered pigs in China was studied. A total of 8,773 samples were collected and examined from different pig abattoirs in 11 provinces from 2009 to 2011. Of these, 4,495 were oral-pharyngeal swab (tonsils) samples from pigs, 1,239 were from intestinal contents, and 3,039 were feces samples from abattoirs or local pigpens. The data showed that 1,132 strains were obtained, from which the isolation rate for Yersinia enterocolitica was 19.53% (878/4,495) from the tonsil samples, 7.51% (93/1,239) from intestinal contents, and 5.30% (161/3,039) from feces. Of the 850 pathogenic Yersinia strains, except for three of bioserotype 2/O:9 and three of bioserotype 4/O:3, most (844/850) were of bioserotype 3/O:3. Interestingly, pathogenic Y. enterocolitica accounted for the majority of the isolated strains from most provinces (85.17% to 100%), whereas from Heilongjiang, 96.52% (111/115) were classified as nonpathogenic biotype 1A with various serotypes, and only 3.48% of the strains (4/115) were pathogenic 3/O:3. All of the pathogenic strains were analyzed using pulsed-field gel electrophoresis (PFGE), and 49 patterns were obtained for the O:3 pathogenic strains; most of them were K6GN11C30021 (53.13%: 450/847) and K6GN11C30012 (21.37%: 181/847). Several strains from diarrhea patient samples revealed PFGE patterns identical to that from samples of local pigs, suggesting a possible link between porcine isolates and human infection. The results above suggested that Yersinia enterocolitica in slaughtered pigs from Chinese abattoirs was characterized by region-specific PFGE patterns and confirmed that strains isolated from pigs are closely related to those from human infections.