1.Factors influencing repeat blood donor lapsing in Guangzhou: based on the zero-inflated poisson regression model
Rongrong KE ; Guiyun XIE ; Xiaoxiao ZHENG ; Yingying XU ; Xiaochun HONG ; Shijie LI ; Yongshi DENG ; Jinyu SHEN ; Jinyan CHEN ; Jian OUYANG
Chinese Journal of Blood Transfusion 2025;38(1):73-78
[Objective] To analyze the influencing factors of repeat blood donor lapsing using a zero-inflated poisson regression model (ZIP). [Methods] The blood donation behavior of 12 498 whole blood donors from 2020 was tracked until December 31, 2023. The factors influencing the frequency of blood donations in a given year was analyzed using ZIP, and donors with 0 blood donation in that year were considered to have lapsed. The changes in relevant influencing factors associated with each blood donation were measured and modeled for analysis. [Results] The zero-inflated part of ZIP showed that the risk of lapsing of male blood donors was 2.24 times that of female blood donors (OR 95% CI:1.864-2.696, P<0.001); the risk of lapsing of the 35-44 age group and over 45 age group was respectively 40% (OR 95% CI:0.455-0.790, P<0.001) and 61%(OR 95% CI:0.268-0.578, P<0.001) lower than that of the under 25 age group; the risk of lapsing for those who have donated blood twice and ≥3 times was respectively 50% (OR 95% CI:0.405-0.609, P<0.001) and 81% (OR 95% CI:0.154-0.225, P<0.001) lower than that of first-time donors; the risk of lapsing of those with junior high or high school education was 1.2 times that of those with a college degree or higher (OR 95% CI:1.033-1.384, P<0.05); the risk of lapsing for the divorced group was 2.02 times that of the married group (OR 95% CI:1.445-2.820, P<0.001); the risk of lapsing for those with an income (Yuan) of 10 000 to 50 000, 50 000 to 100 000 and more than 100 000 was respectively 0.67 (OR 95% CI:0.552-0.818, P<0.001), 0.72 (OR 95% CI:0.591-0.884, P=0.002) and 0.67 (OR 95% CI:0.535-0.834, P<0.001) times that of those with an income (Yuan) of less than 10 000. The results of the Poisson part are consistent with the results of the zero-inflated part in terms of age and education level. [Conclusion] Blood donor lapsing is overall related to factors such as gender, age, donation frequency, education, marital status and family income. It's essential to care for those blood donors prone to lapse to retain more regular blood donors.
2.Characteristics of HIV primary drug resistance and molecular transmission clusters in newly reported men who had sex with men in Taizhou City, Zhejiang Province
Shanling WANG ; Xuanhe WU ; Guixia LI ; Tingting WANG ; Yating WANG ; Tailin CHEN ; Weiwei SHEN ; Yali XIE ; Haijiang LIN ; Na HE ; Xiaoxiao CHEN
Shanghai Journal of Preventive Medicine 2025;37(6):496-502
ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P25, P75)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.
3.Comprehensive Clinical Evaluation of Duliang Soft Capsules in Treatment of Migraine with Wind-cold Blood Stasis Syndrome
Xiaoxiao ZHAO ; Xuming ZHANG ; Junyu XI ; Zhenkai LU ; Fumei LIU ; Lianxin WANG ; Yuanyuan LI ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):223-232
ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome, and to provide guidance for national medical decision-making, clinical drug promotion, and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version, 2021) using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software, this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions, including safety pre- and post-market launch, effectiveness in treating migraine, economy (cost-effectiveness), and innovation, suitability, accessibility, and traditional Chinese medicine (TCM) characteristics in both its technology and clinical applications. ResultSafety: Duliang soft capsules were found to have good safety based on evidence from known adverse reactions (spontaneous reporting system (SRS) data, literature data, etc.), pre-marketing toxicological research, and post-marketing drug monitoring. Effectiveness: A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy: Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation: Duliang soft capsules, with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components, hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction (CO2 supercritical extraction technology) and formulation (soft capsule) processes. The product's innovation was rated as "Better". Suitability: A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility: Duliang soft capsules are moderately priced, making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics: The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio (Shi Zhai Bai Yi Xuan Fang) from the Song Dynasty, and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue (Jing Yue Quan Shu) as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch, and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness, suitability, and accessibility, and outstanding TCM characteristics. The product's safety, economy, and innovation received good ratings. In summary, Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics, the evidence was sufficient, and the result was confirmed, providing crucial references for clinical decision-making and pharmaceutical management.
4.Bidirectional Mendelian randomization study on gut microbiota and constipation
LI Hongmei ; XIAO Qian ; XIE Xiaoxiao ; LIU Chunqiang ; HUANG Yebao
Journal of Preventive Medicine 2024;36(3):198-202
Objective:
To investigate the causal relationship between gut microbiota and constipation using Mendelian randomization (MR) method.
Methods:
Genetic variation data of gut microbiota were obtained from the MiBioGen Consortium database. The genetic variation data of constipation were sourced from the IEU Open GWAS database. A forward MR analysis was performed using the inverse-variance weighted (IVW) method with 2 511 SNPs associated with gut microbiota as instrumental variables, and constipation as study outcome, and a reverse MR analysis was performed with 13 microbiota-associated SNPs as instrumental variables and gut microbiota as study outcome. The heterogeneity was assessed using the Cochran test, reverse causation of SNP were examined using MR Steiger test, and the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression. In addition, the robustness of the results was verified with the leave-one-out.
Results:
Forward MR analysis results showed that an increased abundance of genus Coprococcus1 driven by host genetics was associated with a decreased risk of constipation (OR=0.791, 95%CI: 0.709-0.884), and increased abundance of phylum Bacteroidetes driven by host genetics was associated with an increased risk of constipation (OR=1.240, 95%CI: 1.102-1.394). Cochran test detected no heterogeneity (both P>0.05), MR Steiger test was not revealed reverse causation of SNP, and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (all P>0.05), and the leave-one-out method confirmed the robustness of results. Reverse MR analysis showed no association between gut microbiota and constipation (both P>0.05).
Conclusion
Genus Coprococcus1 and phylum Bacteroidetes in the gut microbiota are associated with constipation.
5.Effects of three rehydration methods on prevention of on-site and delayed blood donation-related vasovagal responses: a cluster-randomized trial
Guiyun XIE ; Shijie LI ; Jian OUYANG ; Fanfan FENG ; Xiaoxiao ZHENG ; Zhiyu ZHOU ; Lianfang MAI ; Jinyan CHEN
Chinese Journal of Blood Transfusion 2024;37(1):43-50
【Objective】 To compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.
6.Treatment failure and drug resistance among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022
Yan LI ; Xuanhe WU ; Lu SHI ; Guixia LI ; Shanling WANG ; Yating WANG ; Tailin CHEN ; Tingting WANG ; Yali XIE ; Weiwei SHEN ; Haijiang LIN ; Xiaoxiao CHEN ; Na HE
Shanghai Journal of Preventive Medicine 2024;36(11):1031-1038
ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age (P25,P75) was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.
7.Prevalence of frailty and related factors in middle-aged and elderly people in island and mountainous areas of Taizhou, Zhejiang Province
Xinyue LIANG ; Qionggui ZHOU ; Liangyou WANG ; Shaling WANG ; Yali XIE ; Xuan YANG ; Jiayu HE ; Zhiyi ZHANG ; Miaochen WANG ; Shuxian HE ; Yunqiu ZHANG ; Tailin CHEN ; Xuanhe WU ; Tingting WANG ; Haijiang LIN ; Xiaoxiao CHEN ; Na HE
Chinese Journal of Epidemiology 2024;45(1):139-147
Objective:To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province.Methods:Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty.Results:A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (a OR=1.55,95% CI: 1.07-2.25, P=0.019). In island area, older age (60-74 years:a OR=2.52,95% CI: 1.56-4.13; ≥75 years:a OR=11.65,95% CI:5.38-26.70), being women (a OR=1.94,95% CI: 1.20-3.17), suffering from depression (a OR=1.09,95% CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: a OR=1.74,95% CI:1.04-2.94;≥75 years: a OR=4.78,95% CI:2.45-9.50). Polydrug use (a OR=2.08,95% CI: 1.14-3.80) and suffering from depression (a OR=1.10,95% CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: a OR=0.40,95% CI: 0.21-0.75; senior high school and technical secondary school: a OR=0.29,95% CI: 0.15-0.53; college or above:a OR=0.22,95% CI: 0.11-0.42). Conclusions:The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.
8.Prevalence and epidemiological characteristics of major chronic diseases in people living with HIV in Taizhou, Zhejiang Province, 1998-2022
Tingting WANG ; Shanling WANG ; Yating WANG ; Yali XIE ; Weiwei SHEN ; Xiaoxiao CHEN ; Xing LIU ; Haijiang LIN ; Na HE
Chinese Journal of Epidemiology 2024;45(7):983-989
Objective:To understand the prevalence of major chronic diseases of diabetes, cardiovascular disease and malignant tumor in people living with HIV in Taizhou.Methods:The data were collected from China Information System for Disease Control and Prevention and Taizhou Chronic Disease Information Management System. A total of 5 126 people living HIV under follow-up in Taizhou from 1998 to 2022 were included in the analysis. Software SAS 9.4 was used for χ 2 test, trend analysis and logistic regression analysis. Results:In the 5 126 people living with HIV, the reported prevalence rates of diabetes,cardiovascular disease and malignant tumor were 10.28% (527/5 126),3.98% (204/5 126) and 6.01% (308/5 126), respectively. 37.00% (195/527) and 48.58% (256/527), 40.20% (82/204) and 48.53% (99/204), 37.66% (116/308) and 48.38% (149/308) were diagnosed as diabetes, cardiovascular disease and malignant tumor before and after confirmation of HIV infection. From 2013 to 2022, the proportion of HIV infected people diagnosed with diabetes, cardiovascular disease and malignant tumor after confirmation increased (trend χ2=79.98, P<0.001; trend χ2=17.44, P<0.001; trend χ2=32.06, P<0.001). Based on the analysis on the factors for complicated chronic diseases in people living with HIV, it was found that women under 60 years old (a OR=0.66, 95% CI: 0.50-0.86) and those with access to antiviral treatment for >5 years before 2016 (a OR=0.54,95% CI:0.37-0.78) were less likely to develop complicated chronic diseases, and those under 60 years old with initial CD4 +T lymphocytes counts <200 cells/μl (a OR=1.32, 95% CI: 1.02-1.70), those aged 40-49 and 50-59 years (a OR=2.88, 95% CI:2.20-3.79; a OR=5.43, 95% CI: 4.10-7.21) as well as those without a record of treatment medication use after 2016 (a OR=1.95,95% CI:1.20-3.16) were more likely to develop complicated chronic diseases. The probability of developing complicated chronic diseases might increase with age in people living with HIV. Conclusions:From 1998 to 2022, there was a certain proportion of complicated chronic diseases among HIV infected individuals in Taizhou, and the proportion of diagnosed cases increased after HIV infection was confirmed. It is necessary to conduct early chronic disease screening, behavior intervention and standardized management in people living with HIV.
9.Effect observation of Kanglaite injection assisted with camrelizumab combined with chemotherapy in the treatment of advanced NSCLC
Xiaoxiao ZHANG ; Zhiwei ZHANG ; Xiaoqian DONG ; Manli XIE ; Wanli DENG ; Ming ZHANG
China Pharmacy 2024;35(15):1882-1887
OBJECTIVE To observe the clinical efficacy of Kanglaite injection assisted with camrelizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS A total of 192 patients with advanced NSCLC and hospitalized in the TCM oncology department of our hospital from January 1st, 2018 to December 1st, 2022 were retrospectively selected as the study objects, and were divided into observation group (additional use, n=104) and control group (without additional use, n=88) according to whether the patients additionally received Kanglaite injection based on camrelizumab combined with chemotherapy (carboplatin+pemetrexed). The short-term therapeutic effects of 2,4 and 6 cycles were compared between the two groups. The levels of peripheral blood immune function indexes and serum tumor markers were compared before treatment, after 3 cycles of treatment and after treatment. The long-term therapeutic effects as well as the occurrence of adverse drug reaction(ADR) during hospitalization were compared between the two groups. RESULTS After 3 treatment cycles and at the end of treatment, the CD4+ T lymphocyte ratio and CD4+/CD8+ in the observation group were notably greater than the control group (P<0.05); the levels of serum carcinoembryonic antigen and cytokeratin 19 fragment antigen 21-1 were significantly lower than those in the control group (P<0.05). The overall survival of the observation group was significantly longer than that of the control group (P<0.05), and the median overall survival was (185.27±38.21) d and (132.11±34.23) d, respectively. There were no significant differences in the whole ADR and grade ≥3 ADR between the two groups during hospitalization(P>0.05). CONCLUSIONS Based on camrelizumab combined with chemotherapy, the addition of Kanglaite injection can enhance immunological response and prolong overall survival in advanced NSCLC patients.
10.Mechanism of Qinggongtang Against Generalized Anxiety Disorder Based on Glu/GABA Metabolic Balance
Xiaoxiao HUANG ; Zhongli XIE ; Mengyue XIE ; Shengzhen LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):28-35
ObjectiveTo investigate the therapeutic effect of Qinggongtang in regulating Glu/GABA metabolic balance and the mechanism of its anxiolytic effect on rat models of anxiety. MethodFifty-four rats were randomly divided into normal, model, diazepam (0.225 mg·kg-1), and low-dose, medium-dose, and high-dose groups of Qinggongtang (5.085, 10.17, 20.34 g·kg-1), with nine rats in each group. Except for the normal group, the other groups were subjected to indeterminate vacutainer stress and chronic restraint stress for 12 days to prepare the anxiety model. On the 3rd day of the stress, 10 days of corresponding drug intervention was started. At the end of the drug treatment, the anxiety level of rats in each group was evaluated by the elevated cross maze experiment (EPM) and the light and dark box experiment (LDB), and the effect of Qinggongtang on the anxiety behavior of rats was preliminarily analyzed. The levels of Glu and GABA in the amygdala tissue of the rats were detected by enzyme linked immunosorbent assay (ELISA), and the changes in the synaptic ultrastructure of the amygdala of the rats in each group were observed by electron microscopy. The mRNA expression of glutamic acid decarboxylase (GAD65 and GAD67), glutamine synthetase (GS), and glutamate transporter-1 (GLT-1) in the amygdala were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and their protein expression was detected by Western blot. ResultCompared with those in the normal group, rats in the model group showed an obvious anxiety state and dull yellow and lusterless fur. They were irritable, easy to anger, and preferred to curl up in the corner. The number of times the EPM entered the open arm and the residence time in the open arm were significantly reduced (P<0.01), and the residence time in the open box and the number of times the LDB went through the box were significantly reduced (P<0.01). The content of Glu in the amygdala was increased (P<0.01), and the content of GABA was reduced (P<0.01). The value of Glu/GAB was elevated (P<0.01), and the number of synaptic and pre-synaptic membrane vesicles in the amygdala was decreased. Sparse dense material in the post-synaptic membrane, increased synaptic gap, slightly disrupted internal structure, and decreased mRNA and protein expressions of GAD65, GAD67, GS, and GLT-1 in the amygdala were observed (P<0.01). Compared with those in the model group, rats in the medium-dose and high-dose groups of Qinggongtang and the diazepam group had bright fur, sensitive reactions, and more active behavior. The number of times EPM entered the open arm and the residence time in the open arm increased significantly (P<0.01), and the residence time in the open box and the number of times the LDB went through the box increased significantly (P<0.01). The content of Glu in all-dose groups of Qinggongtang and the diazepam group decreased (P<0.05, P<0.01), while GABA content increased (P<0.05, P<0.01). The value of Glu/GABA decreased (P<0.01), and the internal and external synaptic structure of each groups of Qinggongtang and the diazepam group was more complete. Synapses and vesicles were numerous, and the synaptic gap was more clearly defined. The efficacy of the high-dose group of Qinggongtang and the diazepam group was the best, and the mRNA and protein expressions of GAD65, GAD67, GS, and GLT-1 in the amygdala were increased in the high-dose group of Qinggongtang and diazepam group (P<0.05, P<0.01). ConclusionQinggongtang can improve synaptic plasticity and affect the expression of GAD65, GAD67, GS, and GLT-1 in the amygdala of rats to regulate Glu/GABA metabolic balance and thus exert anxiolytic effects.


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