1.Safety of endoscopic variceal ligation and endoscopic cyanoacrylate injection in treatment of esophagogastric varices in patients with liver cirrhosis and influencing factors for postoperative bleeding
Luyao JIA ; Baoying CAO ; Chunming HUANG ; Biao XIE ; Hongbo GAO ; Chuo LI ; Qinghua HUANG
Journal of Clinical Hepatology 2026;42(2):356-361
ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation (EVL) or endoscopic cyanoacrylate injection (ECI) for the treatment of esophagogastric varices in patients with liver cirrhosis, as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital, Guangzhou Medical University, from January 2018 to December 2023 were enrolled as subjects, and according to the presence or absence of bleeding after surgery, they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups; the receiver operating characteristic (ROC) curve was plotted to determine the cut-off value of MELD score; a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×109/L and the 103 patients with a platelet count of (25 — 49)×109/L (5 days: 1.94% vs 2.85%, P=0.870; 2 weeks: 2.91% vs 4.92%, P=0.544). The overall bleeding rate was 2.66% (13/489) and 4.50% (22/489), respectively, within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days (odds ratio [OR]=3.726, 95% confidence interval [CI]: 1.214 — 11.429, P=0.021) and 2 weeks (OR=5.760, 95%CI: 1.779 — 18.651, P=0.003) after EVL/ECI, while hemoglobin (Hb) was a protective factor against bleeding within 5 days (OR=0.972, 95%CI: 0.948 — 0.996, P=0.025) and 2 weeks (OR=0.976, 95%CI: 0.957 — 0.995, P=0.016) after surgery; portal vein tumor thrombus (OR=2.667, 95%CI: 1.000 — 7.117, P=0.050) was an independent risk factor for bleeding within 2 weeks after surgery, while platelet count [(25 — 49)×10⁹/L] was not a risk factor for postoperative bleeding (P>0.05). ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI, while Hb is a protective factor; portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.
2.Mechanism of Xuefu Zhuyutang in Intervening in Ferroptosis in Rats with Coronary Heart Disease with Blood Stasis Syndrome Based on ACSL4 Signalling Pathway
Yi LIU ; Yang YANG ; Chang SU ; Peng TIAN ; Mingyun WANG ; Ruqian ZHONG ; Xuejiao XIE ; Qing YAN ; Qinghua PENG ; Qiuyan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):27-38
ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 (ACSL4) signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group, sham-operation group, model group, trimetazidine group (5.4 mg·kg-1), low-, medium-, and high-dose group (3.51, 7.02,14.04 g·kg-1) of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome, and continuous treatment for 7 d was conducted, while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed, and indicators such as electrocardiogram, echocardiography, and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin (HE) staining, and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe2+, lipid peroxidation (LPO), glutathione (GSH), and T-GSH/glutathione disulfide (GSSG) in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species (ROS). Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), ACSL4, and ly-sophosphatidylcholine acyltransferase3 (LPCAT3) in myocardial tissue. ResultsCompared with those in the normal group, the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage, bow-back elevation of the ST segments, elevated T waves, J-point elevation, and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01). Blood rheology showed that the viscosity of the whole blood (low, medium, and high rate of shear) was significantly increased (P<0.01). HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken, and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles, and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased (P<0.01). The content of Fe2+, LPO, and ROS in myocardial tissue was significantly increased (P<0.01). The content of GSH was significantly decreased (P<0.01), and T-GSH/GSSG was decreased (P<0.01). The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased (P<0.05, P<0.01), while those of ACSL4 and LPCAT3 increased significantly (P<0.01). Compared with the model group, the general macroscopic symptoms and electrocardiogram results of rats in low-, medium- and high-dose groups of Xuefu Zhuyutang were alleviated, and the differences in LVEF/LVFS ratios were all significantly increased (P<0.05, P<0.01). The differences in whole-blood viscosity (low, medium, and high rate of shear) were all significantly decreased (P<0.01). The results of HE staining and transmission electron microscopy showed that the morphology, structure, and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). The content of Fe2+, LPO, and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and the content of GSH and T-GSH/GSSG was significantly increased (P<0.05, P<0.01). The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and ACSL4 and LPCAT3 were decreased to different degrees in the low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway, thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.
3.Pharmacovigilance Signal Mining and Analysis of Ustekinumab versus Upadacitinib for Inflammatory Bowel Disease Based on the FAERS Database
Dong XIE ; Yu WANG ; Haojia LIN ; Qiuyue TU ; Hetong ZHANG ; Huizhen LI ; Qinghua YI ; Zhengxiang LI ; Hengjie YUAN ; Xiaocang CAO
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1376-1383
To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety. Data were extracted from the Food and Drug Administration Adverse Event Reporting System(FAERS) database using OpenVigil 2.1. ADE reports were collected for ustekinumab(from Q3 2017 to Q1 2025) and upadacitinib(from Q3 2019 to Q1 2025), where each drug was identified as the primary suspected medication for IBD. Signal detection and statistical analysis were performed using the reporting odds ratio(ROR) and proportional reporting ratio(PRR) methods. A total of 3648 ADE reports for ustekinumab and 3812 for upadacitinib, with each as the primary suspected drug in IBD treatment, were retrieved. Using the ROR-PRR combined detection method, relevant ADE signals were identified. High-frequency ADEs associated with ustekinumab included hypersensitivity reactions, various infections, and brain fog, while those associated with upadacitinib included acne, flatulence, and herpes zoster. System organ class(SOC) analysis of positive signals indicated that both drugs commonly caused ADEs in categories such as Infections and infestations, Gastrointestinal disorders, Nervous system disorders, Skin and subcutaneous tissue disorders, and Respiratory, thoracic, and mediastinal disorders. Among these, Infections and infestations were the most frequent SOC, involving preferred terms such as Escherichia sepsis and Pneumococcal pneumonia. Ustekinumab and upadacitinib exhibit distinct safety profiles in the treatment of IBD. In addition to known ADEs described in the prescribing information, ustekinumab requires close monitoring for hypersensitivity reactions, opportunistic infections, and potential neurological risks. For upadacitinib, attention should be paid to risks of acne, herpes zoster, hypercholesterolemia, and thrombotic events. These findings provide important safety information to support individualized clinical decision-making in IBD management.
4.Analysis on rate of adverse pregnancy outcomes in HIV-infected pregnant women and influencing factors in some regions of China, 2017-2023
Xinwei LI ; Ailing WANG ; Yanli CAO ; Qinghua QIN ; Jiarui ZHENG ; Xiaohua XIE ; Maimaitiming AIBIBAI ; Lingling GUAN ; Xiaoyan WANG ; Dongxu HUANG ; Qian WANG
Chinese Journal of Epidemiology 2025;46(1):125-130
Objective:To understand the incidence of adverse pregnancy outcome in HIV-infected pregnant women and influencing factors in China and provide reference for the improvement of the health status of HIV-infected pregnant women and their newborns.Methods:Based on a mother-child cohort of HIV-infected pregnant women and children (PMTCT-MC-2005) established in Guangxi Zhuang Autonomous Region, Yunnan Province and Xinjiang Uygur Autonomous Region, this study enrolled pregnant women with or without HIV infection as study subjects from January 2017 to June 2023, a total of 1 646 pregnant women (558 HIV-infected and 1 088 HIV-uninfected) were included, and 34 cases with missing data were excluded. The χ2 test was used to analyze the difference in the incidence adverse pregnancy outcome between two groups, and used logistic regression model to identify the influencing factors of adverse pregnancy outcome in HIV-infected pregnant women. Results:A total of 1 612 pregnant women were included in the study, in whom 541 were infected with HIV and 1 071 were not infected with HIV. The incidence of adverse pregnancy outcome was 18.8% (303/1 612), the incidence of adverse pregnancy outcome was 33.1% (179/541) in the HIV-infected pregnant women and 11.6% (124/1 071) in the pregnant women without HIV infection. The results of multivariable logistic regression analysis showed that the influencing factors of adverse pregnancy outcome were age <35 years at delivery (a OR=0.64, 95% CI: 0.43-0.95) compared with the age ≥35 years and the duration of antiviral treatment over 10 years (a OR=0.43, 95% CI: 0.23-0.79) compared with less than one year. Conclusions:The incidence of adverse pregnancy outcome in HIV-infected pregnant women was high in some regions of China during 2017-2023. It is necessary for HIV-infected women to get pregnancy at appropriate time based on antiretroviral treatment effect and strengthen self-care to reduce the incidence of adverse pregnancy outcome.
5.Analysis on rate of adverse pregnancy outcomes in HIV-infected pregnant women and influencing factors in some regions of China, 2017-2023
Xinwei LI ; Ailing WANG ; Yanli CAO ; Qinghua QIN ; Jiarui ZHENG ; Xiaohua XIE ; Maimaitiming AIBIBAI ; Lingling GUAN ; Xiaoyan WANG ; Dongxu HUANG ; Qian WANG
Chinese Journal of Epidemiology 2025;46(1):125-130
Objective:To understand the incidence of adverse pregnancy outcome in HIV-infected pregnant women and influencing factors in China and provide reference for the improvement of the health status of HIV-infected pregnant women and their newborns.Methods:Based on a mother-child cohort of HIV-infected pregnant women and children (PMTCT-MC-2005) established in Guangxi Zhuang Autonomous Region, Yunnan Province and Xinjiang Uygur Autonomous Region, this study enrolled pregnant women with or without HIV infection as study subjects from January 2017 to June 2023, a total of 1 646 pregnant women (558 HIV-infected and 1 088 HIV-uninfected) were included, and 34 cases with missing data were excluded. The χ2 test was used to analyze the difference in the incidence adverse pregnancy outcome between two groups, and used logistic regression model to identify the influencing factors of adverse pregnancy outcome in HIV-infected pregnant women. Results:A total of 1 612 pregnant women were included in the study, in whom 541 were infected with HIV and 1 071 were not infected with HIV. The incidence of adverse pregnancy outcome was 18.8% (303/1 612), the incidence of adverse pregnancy outcome was 33.1% (179/541) in the HIV-infected pregnant women and 11.6% (124/1 071) in the pregnant women without HIV infection. The results of multivariable logistic regression analysis showed that the influencing factors of adverse pregnancy outcome were age <35 years at delivery (a OR=0.64, 95% CI: 0.43-0.95) compared with the age ≥35 years and the duration of antiviral treatment over 10 years (a OR=0.43, 95% CI: 0.23-0.79) compared with less than one year. Conclusions:The incidence of adverse pregnancy outcome in HIV-infected pregnant women was high in some regions of China during 2017-2023. It is necessary for HIV-infected women to get pregnancy at appropriate time based on antiretroviral treatment effect and strengthen self-care to reduce the incidence of adverse pregnancy outcome.
6.Study of the Differences and Mechanisms in Synaptic Plasticity by the Orexin Signalling Pathway in the Rat Models of Insomnia by Using"Raw and Cooked Jujube Kernel"Together and Removing the Formula of AMD
Bo XU ; Kang SUN ; Ping WANG ; Guangjing XIE ; Zijing YE ; Qinghua QIN ; Jing XIA
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(12):3218-3233
Objective To evaluate the effects and the possible mechanisms based on the synaptic plasticity regulated by the orexin signalling pathway of the classic Qing Dynasty prescription AnMeidan(AMD),whose"Raw and cooked jujube kernel"used and without the prescription on learning and memory in a rat model of insomnia.Methods The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine(PCPA)into rats,and AMD was administered by gavage and a decoction of the formula was disassembled.Observing 24 h autonomous activity using the EthoVision XT animal motion trajectory tracking system,Morris water maze was used to evaluate the learning and memory ability;hematoxylin-eosin(HE)and Nissl staining were used to observe the neuronal changes in rat hippocampal CA1 area;Golgi staining and immunohistochemistry(IHC)were used to observe the neuronal dendritic changes in rat hippocampal CA1 area,and the changes in synaptic plasticity proteins,synaptophysin(SYN),microtubule-associated protein 2(MAP-2),glial fibrillary acidic protein43(GFAP-43);Western blotting and Reverse transcription-qPCR(RT-qPCR)were used to detect hippocampal orexin A(OXA)/phosphatidylinositol-specific phosphodiesterase Cβ1(PLCβ-1)/protein kinase Cα(PKCα)/extracellular signalling-regulated kinase(ERK1/2)signalling pathway protein and gene expression.Results Compared with the blank group,the model group showed prolonged upper platform latency,decreased number of crossing stations,decreased distance travelled by periplatform range I activity,the frequency and duration of mania increase,while the frequency and duration of stillness decrease(P<0.01),damaged muscle fibres in the CA1 region of the hippocampus,uneven staining of the nuclei,decreased and disorganized Nyctal microsomes,reduced dendritic spine length and number(P<0.05),and faded staining and decreased expression of SYN,MAP-2,and GFAP-43(P<0.01),hippocampal OXA protein and gene expression increased(P<0.01),and PLCβ-1,PKCα,ERK1/2 protein and gene expression decreased(P<0.01).Compared with the model group,Suvorexant and AMD,AMD desiccated,and cooked jujube seed increased the static frequency、number of times they traversed the station,the distance travelled in the first quadrant and the range of periportal activities,and the time of periportal range I activities(P<0.05,P<0.01);hippocampal muscle fibres were more neatly arranged,the number of Nissin bodies increased,and dendritic spine lengths and numbers were increased(P<0.05),and the SYN,MAP-2,and GFAP-43 expression was elevated(P<0.05,P<0.01),OXA expression was decreased(P<0.01,P<0.05),and PLCβ-1,PKCα,ERK1/2 expression was elevated(P<0.01,P<0.05).Compared with the AMD group,both AMD de-raw and ripe date palm kernel groups could increase the number of times and distances they traversed the stations(P<0.05,P<0.01),decrease the length and number of dendritic spines(P<0.05),decrease the expression of SYN,MAP-2,GFAP-43,and OXA proteins in hippocampal CA1 region(P<0.01),and elevate the PLCβ-1,PKCα,and ERK1/2 expression(P<0.05).Conclusion AMD can regulate the synaptic plasticity of hippocampus in insomniac rats through regulating the OXA/PLCβ-1/PKCα/ERK1/2 signalling pathway to improve the learning memory,the effect of"raw and cooked jujube kernel"used together was better than that of"raw and cooked jujube kernel"used separately.
7.Comparison of rat models of pulmonary fibrosis induced by one or two intratracheal bleomycin instillations
Huimeng TANG ; Qinghua SONG ; Yunyun XIE ; Xin SUN ; Fan YANG ; Shuguang YANG ; Yange TIAN
Acta Laboratorium Animalis Scientia Sinica 2024;32(9):1139-1148
Objective A rat model of pulmonary fibrosis was constructed using a single or two intratracheal drops of bleomycin(BLM)and the modeling rate and stability of the two modeling modalities were compared.Methods A total of 150 specific pathogen-free SD rats were divided randomly into blank control(control),single intratracheal drop of bleomycin(BLM-S),and two intratracheal drops of bleomycin(BLM-M)groups.Rats in the BLM-S group received a single dose of 3 mg/kg BLM by noninvasive intratracheal instillation,and rats in BLM-M group received 3 mg/kg BLM on day 1 and BLM 2 mg/kg on day 14.Rats in the control group were given intratracheal instillation of 0.9%sodium chloride(1 mL/kg).The rats were euthanized on days 28,42,56,and 84 after modelling,respectively.Deep inspiratory capacity(IC),vital capacity(VC),static lung compliance(Cchord),and dynamic lung complication(Cdyn)were measured in all rats.Pathological changes in lung tissue were observed,and the extent of alveolitis and fibrosis was graded.Collagen-Ⅲ(COL-Ⅲ)expression in rat lung tissue was detected by immunohistochemistry.Results(1)The survival rates in the control,BLM-S,and BLM-M groups were 100%,80%,and 66%,respectively.Rats in the BLM-S and BLM-M groups had significantly lower body weights on days 14~42 compared with the control group(P<0.05,P<0.01),and rats in the BLM-M group had significantly lower body weight on days 28~42 than rats in the control and BLM-S groups(P<0.05,P<0.01).(2)Regarding lung function,IC,VC,Cchord,and Cdyn were all markedly decreased in the BLM-S group compared with the control group(P<0.05,P<0.01)and IC,VC,and Cchord were significantly decreased in the BLM-M group(P<0.05,P<0.01)on day 28.IC,VC,and Cchord were significantly decreased in rats in the BLM-S group on day 42(P<0.05,P<0.01),and were also significantly decreased in rats in the BLM-M group on days 42~84(P<0.05,P<0.01).(3)In terms of lung pathology,inflammatory infiltration and fibrous cords appeared in the BLM-S group from days 28~84 and then gradually decreased(P<0.05,P<0.01),while fibrosis and alveolitis were relatively stable in the BLM-M group(P<0.05,P<0.01).(4)COL-Ⅲ expression levels in lung tissue were significantly higher in rats in the BLM-S and BLM-M groups compared with the control group(P<0.05,P<0.01),and the COL-Ⅲ content in the BLM-S group was significantly lower at 42~84 days than at 28 days(P<0.05).Conclusions Both method are capable of effectively creating pulmonary fibrosis models.The single-dose approach is straightforward,has a lower death rate,and the degree of fibrosis is clearly visible by day 28,but progressively recovers after 42 days.In contrast,the two-dose instillation model has a greater success rate and better stability,with over half the rats still exhibiting visible fibrosis on day 84.
8.Comparison of pulmonary fibrosis rat models induced by different dosed of bleomycin
Qinghua SONG ; Huimeng TANG ; Xin SUN ; Yang LIU ; Yunyun XIE ; Yange TIAN
Chinese Journal of Comparative Medicine 2024;34(10):28-37
Objective To compare the success rate and stability of rat pulmonary fibrosis(PF)models induced by intratracheal instillation of different doses of bleomycin(BLM).Methods One hundred and fifty Sprague Dawley rats were divided randomly into control,low-dose BLM 3 mg/kg(BL-L),and high-dose BLM 5 mg/kg(BL-H)groups.General status,mortality,and weight changes were observed,and the lung inspiratory capacity(IC),vital capacity(VC),chord compliance(Cchord),and dynamic compliance(Cdyn)were detected on days 28,42,56,and 84.Lung coefficients were recorded and pathological changes in lung tissue were observed by hematoxylin and eosin and Masson staining.The lung hydroxyproline(HYP)content was detected and collagen type Ⅲ(COL Ⅲ)was detected by immunohistochemistry.Results The mortality rates in the BL-L and BL-H groups were 20%and 28%,respectively.Body weight was significantly lower in the BL-L group compared with the control group on days 0~56,and weight recovery after day 56.Body weight was significantly lower in the BL-H group compared with the control and BL-L groups from days 0~56(P<0.01).Regarding lung function,IC,VC,Cchord,and Cdyn were significantly lower in the BL-L group compared with the control group on day 28(P<0.01,P<0.05),and IC and Cdyn were significantly lower in the BL-H group(P<0.01).IC,VC,and Cchord were significantly decreased in the BL-L group on day 42(P<0.01,P<0.05),while IC,VC,Cchord,and Cdyn were significantly decreased in the BL-H group(P<0.01,P<0.05),and IC,VC,and Cchord were significantly lower compared with in the BL-L group(P<0.01).Cchord was significantly lower in the BL-H group compared with the control and BL-L groups on day 56(P<0.01).The lung coefficients on day 28 were significantly higher in the BL-L and BL-H groups compared with the control group(P<0.01),and were significantly higher in the BL-H group from days 42~56 compared with the BL-L and control groups(P<0.01).Regarding lung histopathology and immunohistochemistry,inflammatory infiltration,fibrotic streaks,and COL Ⅲ expression were observed in the BL-L group from days 28~56,and almost complete disappearance of the fibrotic lesions on day 84.In contrast,fibrotic lesions could be observed from days 28~84 in the BL-H group,with significantly elevated COL Ⅲ expression compared with the control group(P<0.01).The HYP content was significantly higher in the BL-L group compared with the control group from days 28~42(P<0.05,P<0.01),and then gradually decreased,and the HYP content was significantly higher in the BL-H group than in the control group from days 28~84(P<0.01).Conclusions Both 3 and 5 mg/kg BLM can successfully induce PF rat models.Rats treated with 3 mg/kg BLM developed fibrosis on day 28,which lasted until day 42 and then gradually recovered.Rats treated with 5 mg/kg BLM developed fibrosis on day 28,and the degree of fibrosis was more severe with the higher compared with the lower dose,with stable fibrotic lesions up to day 56 and moderate-to-severe fibrosis still present in half of the rats until day 84.
9.Anmeidan Regulates Hepatic Neurotransmitters and Circadian Rhythm in Rat Model of Insomnia via OX1R/PLCβ-1/PKCα/ERK1/2 Signaling Pathway
Bo XU ; Ping WANG ; Jing XIA ; Guangjing XIE ; Zijing YE ; Qinghua QIN ; Jing CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):11-20
ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan (AMD) developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor (OX1R)/phosphatidylinositol-specific phospholipase Cβ-1 (PLCβ-1)/protein kinase Cα (PKCα)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. MethodSixty SPF-grade SD rats were randomized into blank, model, suvorexant (30 mg·kg-1·d-1), and low-, medium-, and high-dose (4.55, 9.09, 18.09 g·kg-1·d-1, respectively) AMD groups, with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine (PCPA) and administrated with corresponding drugs by gavage, and the blank group received an equal volume of normal saline. The general condition, body mass, and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin(HE)staining and Masson staining. The expression of gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), epinephrine (EPI), norepinephrine (NE), and acetylcholine (ACh) in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate (Glu) expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1, Per2, Cry1, Cry2, Bmal1, and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR, respectively. ResultCompared with the blank group, the modeling decreased the body mass (P<0.05, P<0.01) and caused mania and disturbed resting rhythms (P<0.01), hepatic muscle fiber fracture, and edema with inflammatory cell infiltration. In addition, the modeling decreased the GABA, 5-HT, EPI, NE, and ACh content, increased Glu content (P<0.01), down-regulated the mRNA levels of Per1, Per2, Cry1, and Cry2 (P<0.01), up-regulated the mRNA levels of Bmal1 and Bmal2 (P<0.01), and promoted the expression of OX1R, PLCβ-1, PKCα, and ERK1/2 at both protein and mRNA levels (P<0.01). Compared with the model group, suvorexant and AMD increased the body mass (P<0.05, P<0.01), alleviated the mania, and increased the resting time and frequency (P<0.05, P<0.01). Moreover, the medications elevated the levels of GABA, 5-HT, EPI, NE, and ACh, lowered the Glu level, up-regulated the mRNA levels of Per1, Per2, Cry1, and Cry2 (P<0.05, P<0.01), down-regulated the mRNA levels of Bmal1 and Bmal2, and inhibited the expression of OX1R, PLCβ-1, PKCα, and ERK1/2 at both mRNA and protein levels (P<0.05, P<0.01). ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway, and high-dose AMD demonstrated the strongest effect.
10.Factors influencing success of external cephalic version: analysis of 118 cases
Genxia LI ; Panpan ZHAO ; Chunhua CHENG ; Mingkun XIE ; Xianrong MENG ; Qinghua XU ; Jiao LI
Chinese Journal of Perinatal Medicine 2024;27(3):220-225
Objective:To investigate the factors influencing the success of external cephalic version.Methods:Pregnant women who underwent an external cephalic version due to breech or transverse presentation by the same operator in the Third Affiliated Hospital of Zhengzhou University from July 2015 to July 2021 were selected as the study objects. Univariate analysis and logistic regression analysis were used to explore the clinical factors influencing the success of the external cephalic version. The receiver operating characteristic (ROC) curve was used to analyze the best cut-off value of gestational week and amniotic fluid index at the time of operation and to evaluate the predictive value of the influencing factors on the success of the external cephalic version.Results:(1) A total of 118 cases finally entered this study. Among the 118 cases,77 cases (65.3%) succeeded in the external cephalic version, among which the success rate was 49.1% (27/55) for primipara and 79.4% (50/63) for multipara. The vaginal delivery rate was 56.8% (67/118). (2) Complications occurred in 19 (16.1%) of the 118 cases. The main complications were abnormal fetal heart rate (13 cases, 11.0%), umbilical cord presentation, and fetal position reversion (two cases and 1.7% in each), and the serious complications were intrauterine fetal death and placental abruption (one case and 0.8% in each).The complication rate of patients with successful external cephalic version was 7.8% (6/77), which was lower than that of those who failed the external cephalic version [31.7%(13/41)] ( χ 2=11.33, P=0.001). (3) Multivariate analysis showed that gestational week at surgery before 38, amniotic fluid index >11.10 cm, and multipara were the factors affecting the success of the external cephalic version [ OR(95% CI)=0.561(0.351-0.897), 1.173(1.018-1.351) and 4.201(1.547-11.404), all P<0.05]. (4) The area under the ROC curve of the combination of the gestational week at surgery, amniotic fluid index, and parity was 0.744 (95% CI: 0.640-0.848, P<0.001), and the Youden index was 0.518, with a sensitivity of 70.0% and a specificity of 81.8%. Conclusion:Gestational weeks, amniotic fluid index, and multipara are related to the success of the external cephalic version, and the combination of the three has certain predictive power for the success of the surgery.

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