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Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.
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Medicine, Chinese Traditional/adverse effects , Social ChangeABSTRACT
Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.
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Medicine, Chinese Traditional , Cross-Sectional Studies , Treatment Outcome , Case-Control Studies , Narrative MedicineABSTRACT
Xanthine oxidoreductase (XOR), the key enzyme catalyzing purine to produce uric acid, including two subtypes, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), respectively, in vivo. Usually, XDH and XO can transform to each other. In this study, based on the principle that the subtype XO or XDH uses different electron acceptors, the methods for the measuring the activities of bovine milk XOR (pure enzyme) and its subtypes were established. The optimal concentrations of substrate xanthine (50 μmol·L-1) and electron acceptor NAD+ (50 μmol·L-1), pH value (7.80) were investigated. The ranges of the XOR, XO, XDH activity which could be determined were 0.97-17.5 U·L-1, 1-9 U·L-1, and 66-1 191 mU·L-1, respectively. Furthermore, the methods for determining the activities of XOR and its subtypes in mouse liver were established. The preparation of liver samples, the optimal concentrations of xanthine (100 μmol·L-1) and NAD+ (100 μmol·L-1) were researched. And the activity ranges of XOR, XO and XDH in mouse liver which could be determined were 0.67-3.98, 0.19-1.08, and 0.52-3.55 U·gprot-1, respectively. With the methods above, the effects of classic XOR inhibitor allopurinal (Allo) on XOR, XO and XDH from both milk and mouse liver were determined. All animal experiments have been approved by the Animal Experimental Center, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College (00003346). This study established new methods for the determination of XOR and its subtypes activity in pure enzyme system and in mouse liver, respectively, which were accurate and convenient. It laid the experimental foundation for exploring the different pathophysiological effects of XOR in the body and developing new XOR inhibitors.
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Hyperuricemia is not only the biochemical basis of gout, but also closely related to the development of metabolic syndrome, cardiovascular diseases, chronic kidney disease, etc. Xanthine oxidase (XOD) is the key catalytic enzyme for uric acid biosynthesis, therefore the vital target for anti-hyperuricemic drugs. In this study, compound CC18022 was designed and synthesized specifically targeting to XOD. Molecular docking analysis indicated a fairly tight binding between CC18022 and XOD. In the in vitro study, CC18022 significantly inhibited XOD activity with a half maximal inhibitory concentration (IC50) value in the order of nmol·L-1, which is relative to the XOD inhibitor febuxostat. By using both acute and chronic hyperuricemic mice model, compound CC18022 was found to have serum uric acid-lowering effect in a dose-dependent manner in vivo. The animal welfare and experimental processes were in accordance with the provisions of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. In the acute hyperuricemic mice, CC18022 significantly inhibited serum XOD activity, and also the XOD activity in intestine and liver, which were related to purine absorption and metabolism. Therefore, the novel compound CC18022 exhibited significant inhibition on XOD activity and anti-hyperuricemic effects, making it a favorable candidate for further research.
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Medicinal pair is the cornerstone in compatibility of traditional Chinese medicine prescriptions in clinical application.At present,there are many related studies on Chinese medicine for diabetic nephropathy,but they mainly focus on efficacy observation and prescription summary,lacking in-depth study and summary of the mechanism of action of traditional Chinese medicine (TCM).As compared with prescriptions,Chinese medicinal pair has fewer chemical components,a single form,simple mechanism of action,and fewer interference factors.In recent years,TCM has accumulated rich clinical practice experience in the treatment of diabetic nephropathy.Many researchers pay great attention to the application of medicinal pairs in the compatibility of prescriptions and their action rules.Through the compatibility of medicinal pairs,the optimized combinations can be achieved from various aspects to further improve the therapeutic effect of TCM compound.In order to clarify the ways and targets of Chinese medicinal pairs in treatment of diabetic nephropathy,relevant articles at home and abroad were systemically reviewed in this paper.For the clinical observation and animal experiments of the past 10 years,four types of medicines with "invigorating the spleen and the kidney" ,"clearing damp and promoting diuresis" "activating blood and removing stasis" and "securing and astringing" with curative effect for diabetic nephropathy,were mentioned in this article.The composition rules and the progress of experimental researches of these medicinal pairs were analyzed,while the compatibility principles,chemical compositions,and pharmacokinetic changesof the medicinal pairs were summarized to provide some references for their further application,researches and development.
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To investigate the effects of small molecule compound bicyclol on type 2 diabetes mellitus (T2DM) and its mechanism of action, KKAy mice were treated with various doses of bicyclol (100, 200, and 400 mg·kg-1·d-1) with metformin (200 mg·kg-1·d-1) as a positive control, respectively. Age-matched C57BL/6J mice were used as the non-diabetic control (Con). The effect on hyperglycemia was evaluated by the levels of no-fasting blood glucose, fasting blood glucose (FPG), and glucose tolerance. Whole body insulin sensitivity was evaluated by fasting plasma insulin (FPI) and homeostasis model assessment-insulin resistance (HOMA-IR). The hepatic response to insulin was evaluated by insulin-induced activation of insulin signaling pathway. Western blot was performed to detect hepatic protein expressions. All animal experimental procedures were approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. KKAy mice showed T2DM characteristics such as hyperglycemia and insulin resistance, including attenuated response to insulin in the liver. A 28-day treatment of bicyclol suppressed both FPG and no-fasting blood glucose, in a dose- and time-dependent manner. Moreover, FPI and HOMA-IR values were both significantly decreased, and hepatic insulin-induced-phosphorylation of IRβ and Akt were up-regulated in KKAy mice after bicyclol treatment. Phosphorylation of FoxO1, the key transcription factor for regulating gluconeogenesis, was also significantly elevated by bicyclol treatment. These results suggested that bicyclol has some therapeutic effects on hyperglycemia in a time- and dose-dependent manner in KKAy mice. Its mechanism might be attributed to improving insulin resistance, enhancing hepatic insulin signaling pathway, and inhibiting gluconeogenesis. No significant interference on the hypoglycemic effect of metformin by bicyclol was observed in this study.
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Objective:Using an area in east of China as a case,the paper exploit the methodology to define and visualize the scope of the medical insurance pharmacy service through using ArcGIS and its function modules to analy-zing the basic data including this area's population distribution,address of drugstores,administrative districts,road network and soon.Plan A based on the 15-minute walk distance norm for defining the scopes, shows that this area need to increase 548 medical insurances designated drugstore,the effect of which was service area can be increased by 12.36%,service population can be increased by 10.82%, designated drugstore healthy competition rate can be increased by 8.36%;Plan B based on the 10-minute walk distance norm for defining the scopes, displays that this area need to increase 1197 medical insurance designated drugstore, the effect of which was service area can be in-creased by 15.23%,service population can be increased by 20.49%,designated drugstore healthy competition rate can be increased by 19%.
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Objective: This paper develops a methodology for steady and orderly expansion of the designated medical insurance drugstores. Methods:With the help of grid management ideology, the paper uses ArcGIS and its function modules to define and visualize the scope of the medical insurance drugs service with the guidance of fairness and efficiency through analyzing the basic data including population distribution, the physical distribution of drug-stores and soon. Results:In order to figure out the procedure of the methodology,the key problems were all solved, including defining and visualizing the scope of the medical insurance drugs service area,,checking and ratifying the scope that need to supplement or increase the medical insurance drugstores, making measures for the annual imple-mentation and confirming a selection principle for designated medical insurance drugstores. Conclusion:The Method-ology guided by fairness and efficiency of the medicare designated pharmacy layout planning is practical and feasible, which can probably provide a reference for increasing the designated medical insurance drugstores steadily and orderly.
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Objective:To analyze losses and gains (L&G) of basic medical institutions induced by the Essen-tial Medicines Policy.Methods: Choosing some poverty-stricken county in western China as sample area to conduct field research,using 2009 as baseline year,to calculate L&G and L&G ratio of basic medical institutions caused by adjustments of drug policy,medical services prices, and government subsidies from 2009—2015. Results: Medical facilities have gained after the implementation of the Essential Medicines Policy as a whole. Gains were on an upward trend from 2009—2015,and L&G ratio increased from -2.15% in 2009 to 47.70% in 2015. For medical facilities at different levels, their gains attributed to different causes. Gains for medical facilities at village and town levels mainly attributed to government subsidies;gains for medical facilities at county level mainly attributed to adjustment of medical services prices. Conclusions:Implementation of the Essential Medicines Policy has helped adjust composi-tion of losses and gains of medical facilities. Moving forward,functions and development of medical facilities should be strengthened with a focus on adjusting medical services prices for medical facilities at town level.
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<p><b>OBJECTIVE</b>To study the role of p16 gene mutation status as detected by fluorescence in-situ hybridization (FISH) and p16 protein expression as detected by immunohistochemistry in differential diagnosis of malignant mesothelioma and benign mesothelial hyperplasia.</p><p><b>METHODS</b>p16 gene mutation status and protein expression were detected by FISH and immunohistochemistry respectively in 55 cases of pleural malignant mesothelioma and 30 cases of benign mesothelial hyperplasia.</p><p><b>RESULTS</b>FISH study showed that the rate of p16 deletion in malignant mesothelioma (81.8%,45/55) was higher than that in benign mesothelial hyperplasia (3.3%,1/30). The difference was statistically significant (P<0.05). Immunohistochemical study showed that the rate of p16 protein expression in malignant mesothelioma (23.6%) was lower than that in benign mesothelial hyperplasia (76.7%). The difference was also statistically significant. The sensitivity and specificity of FISH in distinguishing between mesothelioma and reactive mesothelial hyperplasia were higher than those of immunohistochemistry.</p><p><b>CONCLUSIONS</b>In contrast to reactive mesothelial hyperplasia, p16 gene is deleted and p16 protein is not expressed in malignant mesothelioma. The sensitivity and specificity of FISH are higher than those of immunohistochemistry in the distinction.</p>
Subject(s)
Humans , Cyclin-Dependent Kinase Inhibitor p16 , Metabolism , Diagnosis, Differential , Epithelium , Pathology , Genes, p16 , Hyperplasia , Diagnosis , Genetics , Immunohistochemistry , In Situ Hybridization, Fluorescence , Mesothelioma , Diagnosis , Genetics , Metabolism , Mutation , Pleura , Pathology , Pleural Neoplasms , Diagnosis , Genetics , Metabolism , Sensitivity and SpecificityABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Ruji Recipe (RR) in preventing disease recurrence/metastasis and improving quality of life (QOL) for female breast cancer patients after operation.</p><p><b>METHODS</b>Totally 102 female patients with stage I - III breast cancer were retrospectively analyzed. They were assigned to the treatment group (54 cases) and the control group (48 cases) according to whether they would rather accept RR therapy. Estrogen receptor/progesterone receptor (ER/PR) positive patients also accepted endocrine therapy. The overall survival (OS), disease-free survival (DFS), recurrence and metastasis, and QOL were compared between the two groups.</p><p><b>RESULTS</b>Totally 100 patients completed the study. The median follow-up was 59 months. The median OS was 60 months in the treatment group and 52.5 months in the control group (chi2 = 3.274, P > 0.05). The median DFS was 55.0 months in the treatment group and 47.5 months in the control group (chi2 = 10.145, P < 0.01). The DFS rate was 75.9% (41/54) in the treatment group and 54.3% (25/46) in the control group (chi2 = -2.259, P < 0.05). There was statistical difference in the 2-, 3-, and 5-year DFS between the two groups (P < 0.01). There was statistical difference in the 2-year DFS 3-year DFS between stage II and III and stage III (P < 0.05, P < 0.01). There was statistical difference in the ER positive patients between 2-year DFS and 3-year DFS (P < 0.01, P < 0.05). There was statistical difference in the 3-and 5-year distant metastasis rate (DMR) in the treatment group, lower than that of the control group (3.7% vs 31.0%, 20.7% vs 60.7%; P < 0.01). By the end of follow-up, disease progression occurred in 13 cases of the treatment group, local recurrence in 3 cases, single organ metastasis in 7 cases, multi-metastasis in 3 cases, while the corresponding numbers were 21, 1, 11, and 9 in the control group (P < 0.05). As for 1 week before study and at 2-year follow-up using Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) system, there was statistical difference in the QOL between the two groups (P < 0.05), and better effect was obtained in the treatment group.</p><p><b>CONCLUSION</b>RR, as an assistant therapy, could improve the OS rate, the DFS rate, and the QOL for post-surgical female breast cancer patients in 2 -3 years.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Breast Neoplasms , Drug Therapy , Mortality , General Surgery , Disease-Free Survival , Drugs, Chinese Herbal , Therapeutic Uses , Neoplasm Metastasis , Neoplasm Recurrence, Local , Phytotherapy , Postoperative Period , Survival RateABSTRACT
Objective To investigate the effect of dietary nutrition on dental fluorosis degrees of school children in endemic fluorosis areas. Methods Two hundred and eight children aged 8 to 12 years were chosen using cluster random sampling method from a village of municipal suburban and a town of autonomous region, both with a history of serious endemic fluorosis. Morning urinary fluoride was measured by fluoride ion electrode. The Tooth Surface Index of Dean was applied to measure the severity of dental fluorosis. Food and nutrient intakes were analyzed according to the 3-day diet records and duplicate meals. Results The urinary fluoride concentration of the children in the town [(6.80±3.90)mg/L]was much higher than those in the village [(5.20±2.75)mg/L, t= 3.21, P < 0.01]. Dental fluorosis index of the children in the town was 1.9, higher than that of the village of 1.8 (H=10.266, P < 0.01). The town had more children with fluoride tooth degree higher than Ⅱ [63.3%(57/90)]than the village did[48.3% (57/118), χ2=4.633, P < 0.05]. A 3-days diet records showed that children in the village ate more protein, calcium, vitamin C and so on but less dietary fiber, vitamin E, magnesium than those in the town did(all P < 0.01). Duplicate meals revealed that children in the town had more daily intake of magnesium, lithium, lead and less cadmium than those of the village did(P < 0.01 or < 0.05). Children in the village had higher intake of fluoride[(2.24±1.18)mg/d]than those of the town [(1.78±0.06)mg/d, t = 4.21, P < 0.01]. Conclusions Healthy diet can reduce the incidence of dental fluorosis or mitigate the degree of the impairment. This study can provide scientific basis for the future control and elimination of endemic fluorosis.
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<p><b>OBJECTIVE</b>To investigate the association of polymorphisms of CDT1 and GMNN gene, two important genes participating in DNA replication, with the risk of sporadic breast cancer.</p><p><b>METHODS</b>Using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis (PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a case-control study of 427 breast cancer cases and 477 cancer-free controls in a Chinese population.</p><p><b>RESULTS</b>No significant association of the CDT1 838G/A and GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95% CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a significant association of CDT1 GA+AA genotypes with breast cancer risk among subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20-4.09).</p><p><b>CONCLUSION</b>These findings suggest that the CDT1 838G/A and GMNN 387C/A polymorphisms may not play a major role in the etiology of breast cancer, but CDT1 variant may have a potential role only in genetically susceptible women.</p>
Subject(s)
Adult , Female , Humans , Middle Aged , Asian People , Genetics , Breast Neoplasms , Ethnology , Genetics , Case-Control Studies , Cell Cycle Proteins , Genetics , China , Geminin , Gene Frequency , Genetic Predisposition to Disease , Genetics , Genotype , Polymerase Chain Reaction , Polymorphism, Genetic , Genetics , Polymorphism, Restriction Fragment LengthABSTRACT
Background and purpose:It was reported that chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1(SDF-1)were involved in the proliferation,differentiation,and metastasis of tumor.This study was designed to observe the expression of chemokine receptor CXCR4 in hypopharyngeal squamous cell carcinoma tissue and study the relationship between the expression of chemokine receptor CXCR4 and different clinicopathlogical characteristics,and further to explore the clinical significance.Methods:For the detection of the expression of chemokine receptor CXCR4,43 primary hypopharyngeal squamous cell carcinoma tissues,27 normal hypopharyngeal tissues,34 lymph node metastastatic lesions and 9 normal lymph node lesions were detected by immunohistochemical method using rabbit anti-human CXCR4 polyclonal antibody.Results:The positive expression rates of CXCR4 in 43 hypopharyngeal carcinoma tissues and normal tissues were 95.3% and 22.2%,respectively(P