OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Humans ; Carcinoma, Hepatocellular/pathology* ; Cell Hypoxia ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Liver Neoplasms/pathology* ; Signal Transduction/genetics* ; tRNA Methyltransferases/metabolism*

Swertia patens Burk. is a commonly used herbal medicine of the Yi nationality in Yunnan, China. It is widely used in the treatment of children with spastic abdominal pain, cholecystitis, and other diseases, mainly containing iridoid glycosides and ketone compounds. The highest and most significant pharmacological activity, with antispasmodic, analgesic, sedative, anti-inflammatory, liver-protecting, stomach-protecting, and other effects, is closely related to its effects of soothing the liver, clearing heat, and relieving stomach pain. As a very distinctive pediatric folk medicine, the related quality standards of Swertia patens Burk. have not been perfected, and the development of preparations is relatively lagging.

ObjectiveTo explore the biological mechanism of drought improving the quality of Rhizoma Atractylodis Chinensis and establish a new method for the production of high-quality medicinal materials. MethodThe fresh roots of Atractylodes chinensis were soaked in 0 （control）， 5%， 10%， and 20% PEG-6000 solutions. The changes in reactive oxygen species （ROS） level， antioxidant enzyme activity， activities of key enzymes in primary metabolism and secondary metabolism， and content of secondary metabolites were compared. ResultCompared with the control group， the treatment with 20% PEG for 2 days elevated the levels of superoxide anion radicals （O2-·）， hydrogen peroxide （H₂O₂）， and malondialdehyde （MDA） by 172.5%， 56.9%， and 14.7%， respectively. The treatment did not change the activity of superoxide dismutase （SOD）， reduced the peroxidase （POD） activity， and increased the catalase （CAT） activity by 10.8%. It increased the activities of 3-hydroxy-3-methylglutaryl-CoA reductase （HMGR）， phosphoenolpyruvate carboxylase （PEPC）， and acetyl-CoA carboxylase （ACC） by 49.9%， 12.1%， and 19.0%， respectively. Furthermore， the content of atractylodin， β-eudesmol， atractylone， and atractylenolide Ⅱ was increased by 51.0%， 36.9%， 47.1%， and 91.5%， respectively. The simulated drought stress can cause the burst of ROS in the fresh roots of A. chinensis， induce the physiological state of plants under drought， change the antioxidant system， and promote the massive synthesis of secondary metabolites in a short time. ConclusionPEG-6000-simulated drought stress can greatly improve the quality of A. chinensis in cultivation.

Objective To investigate the effect of combining electroacupuncture with nerve mobilization to improve lower extremity motor function after sciatic nerve injury. And to document any changes in mRNA and protein expression of Ras-related C3 botoxin substrate 1. Methods 180 New Zealand rabbits were randomly divided into a normal control group, a model control group, an electroacupuncture group, a nerve mobilization group, and an elec-troacupuncture combined with nerve mobilization group, each of 36. Sciatic nerve injury was modelled using the clam-ping method in all except the normal control group. The control group had no intervention, while the nerve mobiliza-tion group, the electroacupuncture group and the combined group were treated with nerve mobilization, and/or elec-troacupuncture applied to the rabbit analogue of the jiaji acupoint. After 1, 2, and 4 weeks of treatment, toe reflex scores and modified Tarlov scores were used to assess any functional recovery. After 1, 2, and 4 weeks of treatment, 12 of the rabbits in each group were sacrificed and the sciatic nerve and the L4-L6 segments of the spinal cord were re-sected. The expression of Ras-related C3 botoxin substrate 1 mRNA and protein was detected using the polymerase chain reaction and western blotting. Results Sciatic nerve function and the expression of Ras-related C3 botoxin sub-strate 1 mRNA in the spinal cords and sciatic nerves of the three treatment groups were significantly higher than in the model control group at all three time points, but significantly lower than in the normal control group. The combined group′s results were significantly better than with electroacupuncture or nerve mobilization alone. After 1, 2, and 4 weeks of treatment, the average expression of Ras-related C3 botoxin substrate 1 protein in the spinal cords of the three treatment groups was significantly higher than the model control group′s average, but significantly lower than that of the normal control group at the same time point. After 1 week of treatment the average expression of Ras-related C3 botoxin substrate 1 protein in the spinal cords of the combined group was significantly higher than that in the group receiving electroacupuncture alone. After 2 and 4 weeks it was also significantly higher than the nerve mobilization group′s aver-age. After 1 week of treatment, the average expression of Ras-related C3 botoxin substrate 1 protein in the sciatic nerves of all three treatment groups was significantly lower than that of the control group. However, 1 and 3 weeks later the av-erage protein expression in the sciatic nerves was significantly higher than in the model control group, but significantly lower than in the normal control group at the same time points. The combined group′s average was then significantly higher than those of the groups receiving electroacupuncture or nerve mobilization alone at the same time point. Conclusion Nerve stimulation combined with electroacupuncture applied to the jiaji acupoint can promote the regener-ation of axons after sciatic nerve injury. The mechanism may be related to up-regulation of the Ras-related C3 botoxin substrate 1 gene and protein expression in the injured sciatic nerve and corresponding spinal cord segments.

OBJECTIVE:To investigate the reliability and validity of the Chinese version Morisky Medication Adherence Scales-8 in assessing medication compliance of the patients with rheumatoid arthritis.METHODS:The Chinese version of MMAS-8 was used to evaluate the compliance of 200 rheumatoid arthritis patients who responded to the WeChat public issue from the public forum of China rheumatism.Item analysis,homogeneity test,reliability analysis,and validity analysis were all conducted.RESULTS:The eight items showed significant difference between the two extreme groups as head and tail 27％ of the total score in Levene method F test (P＜0.001).t test of variance inequality was adopted,with significant difference (P＜0.001).Correlation coefficient between the 7 items and the total score was higher than 0.400,and the 8 items were significantly correlated with the total score (P＜0.001).Internal consistency reliability coefficient Cronbach's α was 0.657,and standardized Cronbach's α was 0.662.For construct validity,KMO was 0.638,Bartlett's sphericity test was 246.278,factor analysis method was adopted to extract 3 common factors,and explainable total variance was 58.846％.Pearson correlation coefficient was 0.435 between MMAS-8 total score and MA-VAS score (P＜0.001).CONCLUSIONS:Reliability and validity of the Chinese version MMAS-8 for the determination of medication compliance in patients with rheumatoid arthritis are good.

Objective To systematically evaluate the risk factors for ovarian metastasis of endometrial carcinoma(EC) to provide an evidence-based medicine basis for formulating the EC surgical mode and ovarian metastatic risk.Methods Studies about the risk factors for EC ovarian metastasis were retrieved by computer from the Pubmed,Embase,Cochrane Library,WanFang database,CNKI,China Biology Medicine(CBM) from Jan.1,1990 to Sep.1,2016.The quality evaluation of included literature was performed by using the Newcastle-Ottawa Scale(NOS).Results A total of 13 studies were included,involving 6 140 EC patients,of whom 344 cases(5.60％) had ovarian metastasis.The Meta analysis results showed that a total of 9 factors had statistical significance,which were deep myometrial infiltration(OR =0.28,95 ％ CI:0.21-0.39),cervical involvement (OR =0.27,95 ％ CI:0.16-0.45),lymph node involvement (OR =0.21,95 ％ CI:0.15-0.27),fallopian tube involvement (OR =0.05,95 ％ CI:0.02-0.10),non-endometrioid adenocarcinoma(OR=0.32,95％CI:0.24-0.43),low differentiation(OR=0.39,95％CI:0.31-0.50),positive ascites cytologic detection(OR=0.14,95％CI:0.09-0.20),high serum CA125 level(OR=0.12,95％CI:0.08-0.19) and lymphovascular cancer embolus(OR =0.34,95 ％ CI:0.23-0.50),the differences were statistically significant(P＜0.05).But the age,lesion location,lesion diameter and estrogenic receptor level had no statistical difference(P＞0.05).Conclusion Deep myometrial infiltration,cervical involvement,lymph node involvement,fallopian tube involvement,non-endometrioid adenocarcinoma,low differentiation and positive ascites cytologic detection,high CA125 level and lymphovascular cancer embolus are the risk factors for EC ovarian metastasis.

Objective To explore the effect and mechanism of exercise preconditioning on neurological deficits in rats after cerebral ischemia-reperfusion. Methods Thirty-six healthy Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12) and exercise preconditioning group (n=12). The latter two groups were occluded middle cerebral artery for 120 minutes and reperfused with modified suture method. The rats were evaluated with Longa's score two, twelve and 24 hours after reperfusion. The expression of mitochondrial ATP-sensitive potassium (mitoKATP) channel proteins inwardly rectifying potassium channel (Kir6.2) and sulphonylurea receptor 1 (SUR1) were detected with Western blotting and the cerebral cell apoptosis was detected with TUENL assay 24 hours after reperfusion. Results Compared with the model group, the Longa's score decreased in the exercise preconditioning group 24 hours after reperfusion (P<0.05), while the expression of Kir6.2 and SUR1 decreased (P<0.05), and TUNEL-positive cells decreased (P<0.05).Conclusion Exercise preconditioning may improve neurological function after cerebral ischemia-reperfusion, which may associate with inhibiting the expression of mitoKATP channel proteins and cell apoptosis.