Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Background: and Purpose To evaluate whether the thrombus enhancement sign (TES) can be used to differentiate embolic large vessel occlusion (LVO) from in situ intracranial atherosclerotic stenosis (ICAS)-related LVO in the anterior circulation of patients with acute ischemic stroke (AIS). Methods: Patients with LVO in the anterior circulation who underwent both non-contrast computed tomography (CT) and CT angiography and mechanical thrombectomy were retrospectively enrolled. Both embolic LVO (embo-LVO) and in situ ICAS-related LVO (ICAS-LVO) were confirmed by two neurointerventional radiologists after reviewing the medical and imaging data. TES was assessed to predict embo-LVO or ICAS-LVO. The associations between occlusion type and TES, along with clinical and interventional parameters, were investigated using logistic regression analysis and a receiver operating characteristic curve. Results: A total of 288 patients with AIS were included and divided into an embo-LVO group (n=235) and an ICAS-LVO group (n=53). TES was identified in 205 (71.2%) patients and was more frequently observed in those with embo-LVO, with a sensitivity of 83.8%, specificity of 84.9%, and area under the curve (AUC) of 0.844. Multivariate analysis showed that TES (odds ratio [OR], 22.2; 95% confidence interval [CI], 9.4–53.8; P<0.001) and atrial fibrillation (OR, 6.6; 95% CI, 2.8–15.8; P<0.001) were independent predictors of embolic occlusion. A predictive model that included both TES and atrial fibrillation yielded a higher diagnostic ability for embo-LVO, with an AUC of 0.899. Conclusion TES is an imaging marker with high predictive value for identifying embo- and ICAS-LVO in AIS and provides guidance for endovascular reperfusion therapy.

Abstract: Objective　To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods　The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results　A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion　Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.
Humans ; Frankincense/chemistry* ; Commiphora ; Resins, Plant/chemistry* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

Objective:To study effects of Orff rhythm-beat-tap training on positive emotions in elderly patients with mild dementia.Methods:Using the convenient sampling method, a total of 72 elderly patients with mild dementia who were treated in the Third People's Hospital of Huzhou from August 2018 to August 2019 were selected as the research objects and they were divided into two groups using the simple random sampling method. After the start of the study, 2 cases dropped out because of failure to persist in training, 1 case dropped out because of transfer during hospitalization and 1 case dropped out because of aggravation of the disease and changing drugs. A total of 68 cases were included in the study, including 33 cases in the intervention group and 35 cases in the control group. The control group received routine nursing, while the intervention group received 12-week Orff rhythm-beat-tap training on this basis. The scores of Positive and Negative Affect Schedule (PANAS) , Apathy Evaluation Scale (AES) and Dementia Mood Assessment Scale (DMAS) were evaluated before and after the intervention.Results:The score of positive emotion after intervention in the intervention group was (31.58±1.87) , higher than (26.66±2.93) in the control group, and the difference was statistically significant ( t=8.297, P<0.01) . After intervention, the score of negative emotion of the intervention group was (21.97±2.30) , the score of apathy was (44.88±5.22) , and the score of dementia mood was (23.18±4.33) , which were lower than (23.80±3.94) , (51.91±7.49) and (26.09±6.20) of the control group, and there were statistically significant differences in scores between the two groups ( t=-2.356, -4.514, -2.225; P<0.05) . Conclusions:Orff rhythm-beat-tap training is suitable for elderly patients with mild dementia, which can effectively enhance positive emotional experience of patients, improve apathy and optimize mood.

Objective:To determine whether glutathione dehydrogenase (GLDH), purine nucleotide phosphorylase (PNP), α-glutathione-S-transferase (α-GST), and arginase 1 (Arg1) can be used as the early biomarkers of drug-induced liver injury by comparing the changes of traditional biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin (TBIL) and potential biomarkers GLDH, PNP, α-GST and Arg1 in acetaminophen (APAP)-induced liver injury model rats. Method:The 48 rats were randomly divided into two groups:blank group and model group. 24 rats in each group, half male and half female. The model group received 1 250 mg·kg^-1 APAP solution by intragastric administration to establish the drug-induced liver injury. 6 rats (half male and half female) were randomly selected from each group at 3, 6,12 and 24 h after APAP was given to the model group, to detect the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST, Arg1 in serum and levels of GLDH, PNP, α-GST, Arg1 in liver tissue homogenate at each time point Histopathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. Result:As compared with the blank group, the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST and Arg1 in serum and liver homogenates were significantly increased in model group(P<0.05,P<0.01), indicating that the APAP-induced liver injury model was successfully replicated. GLDH, PNP, α-GST and Arg1 levels in serum and liver tissues of rats in the model group were increased earlier and more significantly than ALT and AST levels. Conclusion:GLDH, PNP, α-GST and Arg1 can be used as biomarkers for early detection of drug-induced liver injury.

Objective:To replicate the animal model of liver injury in rats by using carbon tetrachloride (CCl₄), investigate the dynamic changes of early biomarkers of liver injury, namely glutamate dehydrogenase (GLDH), purine nucleotide phosphorylase(PNP), α-dynamic changes of glutathione-S-transferase (α-GST) and arginase 1(Arg1), and provide experimental evidence for early detection of acute liver injury. Method:Forty-eight Wistar rats were randomly divided into a blank group and a model group. The model group was intraperitoneally injected with 10 mL·kg^-1 10% CCl₄ olive oil solution, fasting but except water. Animals were sacrificed at 3, 6, 12, and 24 h. The serum liver function alanine aminotransferase(ALT), aspartate aminotransferase (AST), bilirubin (TBIL), alkaline phosphatase (ALP) levels, α-GST, Arg1, GLDH, PNP levels, and liver homogenate superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) levels were then detected. Result:As compared with blank group, the levels of ALT, AST, TBIL, α-GST, Arg1, GLDH, PNP and MDA were increased significantly 3 h after administration, and SOD was decreased significantly(P<0.01). After 6,12 h, the levels of ALT, AST, α-GST, ARG-, GLDH, TBIL, ALP and MDA were increased significantly, while GSH and SOD were decreased significantly (P<0.05, P<0.01). After 24 h, the levels of ALT, AST, α-GST, Arg1, TBIL, ALP and MDA were significantly increased, while GSH and SOD were significantly decreased (P<0.01). Conclusion:α-GST, Arg1, GLDH and PNP have better sensitivity than traditional liver function test indicators, and can be used for early detection of liver injury induced by CCl₄ in rats.

Objective:To investigate the dynamic changes of the biomarkers of alcoholic liver injury, including glutamate dehydrogenase(GLDH), α-glutathione-S-transferase(α-GST), purine nucleotide phosphorylase(PNP), and arginine enzyme 1(Arg1), and clarify whether these indexes can be used as early diagnostic biomarkers for alcoholic liver injury. Method:48 Wistar rats were randomly divided into a blank group and a model group, 24 rats in each group, half male and half female. After fasting but except water for 7 h, 50% ethanol/10 mL·kg^-1 was given to the model group by intragastric administration and the same volume of normal saline was administered to the blank group. After 1 h, 50% ethanol was again given for once by intragastric administration according to the previous dosage. In the blank group, the same volume of normal saline was administered. After modeling and administration for 6 d, acute alcoholic liver injury model was established. 3 h after the last intragastric administration of alcohol at day 2, 3, 4, 6, six rats (half male and half female) in each group were randomly selected. All the animals were sacrificed to determine the aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), bilirubin(TBIL), GLDH, α-GST, PNP, and Arg1 levels. Result:As compared with the blank group, the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST and Arg1 in the model group were significantly different (P<0.01), indicating that the alcoholic liver injury model was successfully established. In the model group, GLDH, PNP, α-GST and Arg1 levels were increased earlier and more significantly than ALT and AST levels. Conclusion:GLDH, PNP, α-GST and Arg1 can be used as biomarkers for early detection of alcoholic liver injury.