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.

Objective To investigate the expression of CD123 in children with acute lymphoblastic leukemia(ALL)and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia(B-ALL).Methods A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology,Children's Hospital of Kunming Medical University,from December 2019 to June 2022.According to the expression of CD123 at initial diagnosis,the children were divided into CD123+group and CD123-group,and the two groups were compared in terms of clinical characteristics and treatment outcome.The factors influencing the prognosis were analyzed.Results Among the 251 children with ALL,there were 146 children(58.2%)in the CD123+group.The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group(P<0.05).Compared with the CD123-group,the CD123+group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years,with a relatively low proportion of children with E2A-PBX1 fusion gene(P<0.05).The multivariate Cox proportional-hazards regression model analysis showed that compared with the>10 years group,the 1-10 years group had a significantly higher overall survival rate(P<0.05),and compared with the high risk group,the moderate risk group had a significantly higher event-free survival rate in children with B-ALL(P<0.05).Conclusions CD123 is widely expressed in children with B-ALL,and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL,which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Aim To explore the effect of ginsenoside Rg3 on the biological behavior of human gastric cancer SGC-7901 cells by regulating E2F1.Methods MTT assay was used to determine the effect of ginsenoside Rg3(0,80,160,320 μmol·L-1)on cell prolifera-tion.The effects of different concentrations of ginsen-oside Rg3 on apoptosis were measured by flow cytome-try.The effects of different concentrations of ginsen-oside Rg3 on cell migration and invasion were deter-mined by scratch healing experiment and Transwell ex-periment.The effects of different concentrations of gin-senoside Rg3 on the expression of E2F1,MMP-2,MMP-9,BCL-2 and Bax were determined by Western blot.Results Compared with the blank control group,the cell survival rate of 80,160 and 320 μmol ·L-1 ginsenoside Rg3 group was significantly lower,and it was concentration-dependent(P＜0.05).Com-pared with the blank control group,the apoptosis rate of 80,160 and 320 μmol·L-1 ginsenoside Rg3 group significantly increased in a concentration-dependent manner(P＜0.05).Compared with the blank control group,the number of cell migration in 80,160 and 320 μmol·L-1 ginsenoside Rg3 groups was significantly lower in a concentration-dependent manner(P＜0.05).Compared with the blank control group,the number of cell invasion in 80,160 and 320 μmol· L-1 ginsenoside Rg3 groups was significantly lower in a concentration-dependent manner(P＜0.05).The E2F1 mRNA and E2F1 protein expression in the 80,160,and 320 μmol·L-1 ginsenoside Rg3 groups were significantly reduced in a concentration-dependent manner compared with that in the blank control group(P＜0.05).The protein expression of MMP-2,MMP-9,and BCL-2 in the cells of 80,160,and 320 μmol ·L-1 ginsenoside Rg3 group significantly decreased compared with those of the blank control group,and BCL-2 significantly increased compared with that of the blank control group in a concentration-dependent man-ner(P＜0.05).Conclusions Ginsenoside Rg3 can reduce the proliferation,inhibit the migration and inva-sion of gastric cancer SGC-7901 cells,and promote the apoptosis of SGC-7901 cells in a concentration-depend-ent manner,and its mechanism may be related to the down-regulation of MMP-2,MMP-9,and BCL-2 ex-pression and up-regulation of Bax expression through E2F1.

Objective: To understand and analyze the incidence of club drug abuse and influencing factors in men who have sex with men (MSM) in Qingdao, and provide reference for the AIDS prevention and intervention in this population. Methods: From March 2017 to July 31, 2022, MSM who did not abuse club drug were recruited by snowball sampling of MSM social organizations in Qingdao, a prospective cohort was established, and a follow-up survey was conducted every 6 months. The survey collected the information about the MSM's demographic characteristics, sexual characteristics, club drug abuse and others. The incidence of club drug abuse was the outcome dependent variable and the interval between the recruitment into the cohort and the incidence of club drug abuse was the time dependent variable. Cox regression analysis was conducted to identify the influencing factors for club drug abuse. Results: A total of 509 MSM were recruited at baseline survey, and 369 eligible MSM were enrolled in this cohort. A total of 62 MSM began to abuse club drug during the study period, and the cumulative follow-up time was 911.54 person-years, the incidence of club drug abuse was 6.80/100 person-years. All the club drug abusers shared drugs with others in the first club drug abuse, and 16.13% (10/62) had mix-use of club drugs. The multivariate Cox proportional risk regression analysis showed that being students (aHR=2.17, 95%CI: 1.15-4.10), receiving no HIV testing or receiving 1 HIV testing during past 6 months (aHR=4.57, 95%CI:1.80-11.60; aHR=5.15, 95%CI: 2.83-9.36), having sex only with regular sexual partners during past 6 months (aHR=4.75,95%CI:2.32-9.75), having more than 4 homosexual partners (aHR=1.70, 95%CI:1.01-2.87) and abuse of club drug of sexual partners during past 6 months (aHR=12.78, 95%CI:3.06-53.35) were significantly associated with club drug abuse in the MSM. Conclusions: The incidence of club drug abuse was at a high level in the MSM cohort in Qingdao, indicating a high risk for HIV infection. Being student, receiving less HIV testing, having sex only with regular sexual partners, having more homosexual partners and abuse of club drug of sexual partners during past 6 months were risk factors for the incidence of club drug abuse in the MSM. Targeted surveillance and intervention measures should be strengthened to reduce the risk of club drug abuse in MSM.
Male ; Humans ; Homosexuality, Male ; Cohort Studies ; Illicit Drugs ; Incidence ; HIV Infections ; Prospective Studies ; Sexual and Gender Minorities ; Substance-Related Disorders

Objective: To analyze associated factors and adverse pregnancy outcomes of postpartum hemorrhage in the caesarean section of puerperae with different types of placenta previa. Methods: This retrospective research was a case-control study. Puerperae with cesarean section of placenta previa from January 2019 to December 2020 in Women's Hospital, School of Medicine, Zhejiang University were collected and divided into the<1 000 ml control group or ≥1 000 ml postpartum hemorrhage group according to the amount of blood loss during cesarean section. Differences in continuous variables were analyzed by t-test and categorical variables were analyzed by χ² test. The risk factors of postpartum hemorrhage were analyzed by logistic multivariate regression. Results: A total of 962 puerperae were enrolled with 773 cases in the control group and 189 cases in the postpartum hemorrhage group. The incidence of gestational weeks, gravidity, parity, induced abortion, placental accreta and preoperative hemoglobin<110 g/L was significantly different between two groups in different types of placenta previa (P<0.001). Logistic multivariate regression model analysis showed that the independent risk factors of postpartum hemorrhage in the caesarean section of low-lying placenta included placental accreta (OR=12.713, 95%CI: 4.296-37.625), preoperative hemoglobin<110 g/L (OR=2.377, 95%CI: 1.062-5.321), and prenatal vaginal bleeding (OR=4.244, 95%CI: 1.865-9.656). The independent risk factors of postpartum hemorrhage in the caesarean section of placenta previa included once induced abortion (OR=2.789, 95%CI:1.189-6.544), induced abortion≥2 (OR=2.843, 95%CI:1.101-7.339), placental accreta (OR=6.079, 95%CI:3.697-9.996), HBsAg positive (OR=3.891, 95%CI:1.385-10.929), and placental attachment to the anterior uterine wall (OR=2.307, 95%CI:1.285-4.142). The rate of postpartum hemorrhage and premature delivery in puerperae with placenta previa was higher than that in puerperae with low-lying placenta (P<0.001). Conclusions: The associated factors of postpartum hemorrhage in puerperae with different types of placenta previa are different. Placenta accreta is the common risk factor of postpartum hemorrhage in puerperae with low-lying placenta and placenta previa.
Female ; Pregnancy ; Humans ; Cesarean Section ; Postpartum Hemorrhage/surgery* ; Pregnancy Outcome ; Retrospective Studies ; Case-Control Studies ; Placenta Previa/surgery* ; Placenta ; Risk Factors

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl₄-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

A quantitative analysis method for six principal active constituents (acubin, geniposidic acid, chlorogenic acid, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside) of crude Eucommiae Cortex (EC) and its salt-processed product extracts was developed to investigate and compare their pharmacokinetic behaviors in adenine-induced renal fibrotic rats in vivo. UHPLC-QqQ-MS/MS technology was employed. Scan was conducted in negative ion mode and quantitative determination was carried out by MRM paired ion. The established method was fully validated by specificity, linearity, precision, accuracy, stability, recovery, and matrix effect, and the results of methodological investigation met the requirements of biological sample analysis. Then, a quick, sensitive, and accurate method was successfully established, which could simultaneously measure the contents of six active constituents of crude and salt-processed EC extracts in rat plasma. After a single administration to renal fibrotic rats of crude EC and its salt-processed product extracts, the plasma concentration of each constituent at different time points was measured, the pharmacokinetic parameters were calculated and the concentration time curves were structured. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that compared to the crude Eucommiae Cortex group, the t_max of aucubin, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside in the salt-processed Eucommiae Cortex group rat plasma were significantly lower than those in the crude group (P < 0.05, P < 0.01); the C_max and AUC_{0-48 h} of chlorogenic acid, the C_max, AUC_{0-48 h} and AUC_0-∞ of pinoresinol di-O-glucopyranoside, and the C_max of geniposide and pinoresinol 4-O-glucopyranoside were significantly higher than those in the crude group (P < 0.05, P < 0.01). Our investigation found that compared to crude Eucommiae Cortex, a variety of active ingredients could play a role of quick effect with higher peak blood concentration and bioavailability after oral administration of salt-processed Eucommiae Cortex, which were consistent with the traditional Chinese medicine theory of "salt-processing enhancing drug into kidney meridian", providing an experimental basis for the selection of quality control indexes and the in-depth study of processing mechanisms and metabolic rules in vivo of Eucommiae Cortex and its salt-processed product.

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.
Rats ; Animals ; Rats, Inbred SHR ; Paraventricular Hypothalamic Nucleus/physiology* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Rats, Inbred WKY ; Corticotropin-Releasing Hormone/metabolism* ; Neurons/physiology* ; Hypertension ; Sympathetic Nervous System

Objective By review of the studies comparing the measurements properties of EuroQol five-dimensional questionnaire (EQ-5D) and short-form 6-dimension health survey (SF-6D) in Chinese populations,this study aims to provide a reference for selecting,applying,and improving the health-related quality of life and health utility measurement tools for Chinese populations.Methods We retrieved the original studies which compared the two tools from both Chinese and English databases and then summarized the findings of the included studies from the measurement properties.Results A total of 12 studies were screened out,including 9 studies about diseased populations and 3 studies about the general populations.The included studies generally demonstrated that both EQ-5D and SF-6D had good feasibility,while the utility scores generated from them cannot be used interchangeably.For the diseased populations,both EQ-5D and SF-6D and their utility scores had good construct validity,including convergent and known-groups validity,while only the utility scores had good construct validity for the general populations.For the diseased populations,SF-6D had smaller ceiling effect and better sensitivity than EQ-5D-3L,while the comparison results between SF-6D and EQ-5D-5L were inconsistent.For the general populations,SF-6D also had better sensitivity than EQ-5D.In addition,there was little comparative evidence for reliability such as test-retest reliability and responsiveness between SF-6D and SF-6D in the two populations.Conclusion This review summarized the characteristics,methods,results,and conclusions of the studies that directly compared the two tools for the populations in China.Although only the studies directly comparing EQ-5D and SF-6D are included in this review,the common findings in these studies provide a basis for better comparison between the two in the future.

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.