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.

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.

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*

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 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.

Objective To investigate the effect of acupuncture-rehabilitation therapy on the neurological function and the expression of cleaved-caspase-8, cleaved-caspase-3 and cellular inhibitor of apoptosis 1 (cIAP1) in ischemic penumbra of rats with cerebral ischemia. Methods A total of 90 male Sprague-Dawley rats were randomly divided into sham group, model group, acupuncture group, rehabilitation group and acupuncture-rehabilitation group. Each group was divided into three days, seven days and 14 days subgroups (n=6). The cerebral ischemia model was established with the modified Koizumi suture method. The sham group and the model group received no treatment. The acupuncture group received cluster needling of scalp acupuncture, the rehabilitation group received treadmill training, and the acupuncture-rehabilitation group received both acupuncture and treadmill training. Three days, seven days and 14 days after modeling, their neurological function was assessed with modified Neurological Severity Score (mNSS) and Rota-rod test, and the expression of cleaved-caspase-8, cleaved-caspase-3 and cIAP1 protein in cerebral ischemic penumbra were detected with Western blotting. Results Compared with the model group, the mNSS scores decreased, the retention time of Rota-rod test increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein decreased and the expression of cIAP1 protein increased in each treatment group at each time point (P<0.05). Compared with the other two treatment groups, the mNSS scores further decreased, the retention time further increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein further decreased, and the expression of cIAP1 protein further increased (P<0.05) seven days and 14 days after modeling in the acupuncture-rehabilitation group.Conclusion Acupuncture-rehabilitation therapy can improve the neurological function in rats with cerebral ischemia, that is better than the simple acupuncture or exercise, which may relate to the inhibition of caspase-8 and caspase-3 protein activation, and promotion of cIAP1 protein expression, to inhibit the apoptotic caspases cascade reaction.

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 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.

OBJECTIVETo assess the value of combined fetal karyotyping and chromosomal microarray analysis (CMA) for the verification of high-risk pregnancy signaled by noninvasive prenatal screening (NIPS) based on high-throughput sequencing.

METHODSOne hundred and fifty-one pregnant women with high risks for aneuploidies of chromosomes 13, 18, 21, X and Y or pathological copy number variations (CNVs) by NIPS were subjected to amniocytic karyotyping and CMA analysis.

RESULTSOne hundred and forty-two women were found to have a high risk for fetal chromosomal aneuploidies, which included 83 cases of trisomy 21, 17 cases of trisomy 18, 2 cases of trisomy 13, and 40 cases of sex chromosome aneuploidies. Amniocytic karyotyping and CMA analysis has confirmed 81 cases of trisomy 21, 15 cases of trisomy 18, 10 cases of 47,XXY, 4 cases of 47,XXX, 2 cases of 47,XYY and 1 case of 46,X,del(X)(q26.1). Two trisomy 21, two trisomy 18, 2 trisomy 13, and 23 cases of sex chromosomal aneuploidies were verified as false positives. For 9 women with pathological fetal CNVs detected by NIPS, combined fetal karyotyping and CMA has confirmed 1 case of chromosome 13 microdeletion, 1 case of chromosome 18 microduplication, and 1 case of chromosome 18 deletion. For a case with 30 Mb duplication of chromosome 2 and 25 Mb duplication of chromosome 8, CMA analysis had no positive finding, while fetal umbilical cord blood karyotyping has yielded a 46,XX,dup(2)(p23.1p25.3)[13]/46,XX[87] karyotype. The remaining 5 cases were confirmed as false positive results.

CONCLUSIONCombined fetal karyotyping and CMA has provided a powerful tool for verifying high-risk fetuses signaled by NIPS.

Aneuploidy ; DNA Copy Number Variations ; Down Syndrome ; Female ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis ; Trisomy 13 Syndrome ; Trisomy 18 Syndrome