1.Mechanisms of Improving Hippocampal Synaptic Plasticity Through GLP-1/GLP-1r Pathway to Alleviate Anxiety and Depression-like Behaviors in Chronic Restraint Stress Rats by Xiaoyaosan
Hao WANG ; Yanan YAN ; Jiepeng WANG ; Chaoyi FANG ; Fang FANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):34-42
ObjectiveTo observe the effects of Xiaoyaosan on glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1r) and protein kinase A (PKA)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways in the hippocampal CA1 region of rats under chronic restraint stress (CRS),and to explore the mechanism of this formula to alleviate anxiety and depression-like behaviors. Methods40 specific pathogen-free male Sprague-Dawley (SD) rats were randomly divided into normal,model,Xiaoyaosan,and fluoxetine groups,with 10 rats in each group. CRS was used to induce anxiety and depression-like behaviors. The rats in the Xiaoyaosan group were gavaged with aqueous solution of traditional Chinese medicine formula granules (7.36 g·kg-1·d-1),while those in the fluoxetine group were gavaged with aqueous solution of fluoxetine (2 mg·kg-1·d-1). Body weight was measured on days 0,7,14,and 21 of the experiment. On days 0 and 22 of the experiment,the sucrose preference test (SPT),forced swimming test (FST),and open field test (OFT) were performed. The pathological morphology of the hippocampal CA1 region was observed by Nissl staining. The relative mRNA expression of post-synaptic density protein-95 (PSD95) and synapsin (SYP) was detected by reverse transcription quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect expression of proteins in the GLP-1/GLP-1r and PKA/CREB/BDNF pathways in the hippocampal CA1 region. ResultsAfter CRS modeling,compared with the normal group,the rats of the model group had anxiety and depression-like behavioral manifestations,neuronal damage in the hippocampal CA1 region,significantly downregulated expression of synaptic plasticity markers PSD95 and SYP genes (P<0.01),and inhibition of GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways (P<0.05,P<0.01). Compared with the model group,the Xiaoyaosan group exhibited alleviated anxiety and depression-like behaviors,reduced neuronal damage in the hippocampal CA1 region, significantly increased expression of PSD95 and SYP genes (P<0.01),and the activation of the GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways (P<0.05,P<0.01). ConclusionXiaoyaosan can alleviate anxiety and depression-like behaviors in CRS rats by improving synaptic plasticity in the hippocampal CA1 region. The mechanisms may be related to the activation of the GLP-1/GLP-1r pathway and its mediated PKA/CREB/BDNF signaling pathway by the formula.
2.Analysis on the Disease-Syndrome-Quantity Pattern of TCM Compounds for Ischemic Stroke Based on Complex Network
Runze ZHANG ; Chenming HE ; Shuang ZHOU ; Liang ZHU ; Jielian LUO ; Liang LIU ; Wei DENG ; Yanan LI ; Bangjiang FANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):45-51
Objective To study the medication law of TCM compounds for ischemic stroke using data mining methods;To provide reference for clinical medication.Methods Literature about TCM treatment for ischemic stroke was retrieved from CNKI,VIP,Wanfang Data and SinoMed from May 31,2014 to May 31,2024.Drug frequency analysis,dosage analysis,property and taste attribution analysis,association rule analysis,factor analysis and clustering analysis were performed using Excel 2019,SPSS Modeler 18,SPSS 25 software.Results A total of 180 prescriptions for the treatment of ischemic stroke were included,involving 208 kinds of Chinese materia medica,with a total frequency of 1 996 times,of which 20 were high-frequency medicines(≥24 times),with Chuanxiaong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix,Paeoniae Radix Rubra and Carthami Flos being the most frequent;the efficacy of the medicines included activating blood circulation and removing blood stasis,tonifying the deficiency,pacifying the liver,calming the wind and clearing away heat;the main properties were warm,cold and neutral;the main tastes were bitter,sweet and pungent;the main meridians were liver,spleen,heart and lung meridians;among the drug dosages of drugs with frequency≥24,the mean dosage of Chuanxiong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix and Paeoniae Radix Rubra were 12.24,12.91,10.52,40.00,12.13 g,respectively.In the systematic clustering and complex network analysis,it was suggested that the core TCM prescriptions were:Xuefu Zhuyu Decoction with modified Banxia Baizhu Tianma Decoction,modified Chaihu Shugan Powder,Buyang Huanwu Decoction with modified Huangqi Guizhi Wuwu Decoction and modified Liujunzi Decoction.Conclusion TCM treatment for ischemic stroke mostly uses the methods of activating blood circulation and expelling phlegm,nourishing blood to promote blood circulation,clearing heat and cooling blood,and benefiting qi and neutralizing qi,which provides ideas and methods for following research.
3.Effects of Zuogui Jiangtang Tongmai Prescription on Short-chain Fatty Acids and G Protein-coupled Receptor 109A in Diabetic Atherosclerotic Mice
Jing CHEN ; Qin WU ; Yanan ZHANG ; Jingjing YANG ; Yanling CHEN ; Wuchaonan LIU ; Fang LEI ; Dingxiang LI ; Yihui DENG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(3):76-82
Objective To investigate the effects of Zuogui Jiangtang Tongmai Prescription on short-chain fatty acids(SCFAs)and G protein-coupled receptor 109A(GPR109A)in diabetic atherosclerotic mice;To explore its mechanism of improving diabetic atherosclerosis.Methods ApoE-/-mice were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to establish atherosclerosis model of diabetes.After modeling,the mice were randomly divided into the model group,Western medicine group(metformin hydrochloride+atorvastatin),and Zuogui Jiangtang Tongmai Prescription low-,medium-and high-dosage groups(19,38,76 g/kg);and the other C57BL/6J mice were set as the control group,with 6 mice in each group.Each group was given solution for gavage,once a day for 4 weeks.Blood glucose of the mice were detected,HE staining was used to observe the morphology of the aorta,TG,TC,LDL-C and HDL-C contents were detected by fully automated biochemistry analyzers,ELISA was used to detect the contents of serum HbA1c,fasting insulin(FINS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α,gas chromatography was used to detect the content of intestinal SCFAs,and RT qPCR and Western blot were used to detect the mRNA and protein expressions of GPR109A in ileal tissue and nuclear factor(NF)-κB p65 in aortic tissue,respectively.Results Compared with the control group,obvious plaques and inflammatory cells infiltration were seen in the aorta of the model group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents increased(P<0.01),FINS and HDL-C content decreased(P<0.01),intestinal acetate,propionate,butyric acid,isobutyric acid and isovaleric acid contents decreased(P<0.01),GPR109A mRNA and protein expression in ileal tissue decreased,NF-κB p65 mRNA and protein expression in aortic tissue increased(P<0.01).Compared with the model group,the aortic plaque area and inflammatory cells infiltration were significantly improved in each drug intervention group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents decreased(P<0.05,P<0.01);the FINS and HDL-C content increased(P<0.05,P<0.01),intestinal acetic,propionic,butyric acid,isobutyric acid and isovaleric acid contents increased(P<0.05,P<0.01),GPR109A mRNA and protein expression in ileal tissue increased and NF-κB p65 mRNA and protein expression in ileal tissue decreased decreased(P<0.05,P<0.01).Conclusion Zuogui Jiangtang Tongmai Prescription can improve glucolipid metabolism and inflammatory response in diabetic atherosclerotic mice,which may be related to regulating SCFAs/GPR109A pathway.
4.Predictive value of TGF-β1,CBX7,and suPAR for postoperative recurrence of cervical intraepithelial neoplasia after cervical conization
Yanan ZHI ; Fang FENG ; Jiawen PENG ; Yang WANG ; Pan LIU
International Journal of Laboratory Medicine 2025;46(14):1694-1701
Objective To explore the predictive value of transforming growth factor beta 1(TGF-β1),chromobox homolog 7(CBX7),and soluble urokinase type plasminogen activator receptor(suPAR)for post-operative recurrence of cervical intraepithelial neoplasia after cervical conization.Methods A total of 200 pa-tients with cervical intraepithelial neoplasia admitted to the hospital from April 2020 to June 2023 were select-ed as the research subjects.All patients were treated with cervical conization.All patients were followed up for one year.According to the postoperative recurrence of cervical intraepithelial neoplasia patients after cervical conization,they were divided into the recurrence group and the non-recurrence group.Univariate and multiva-riate Logistic regression analyses were conducted to analyze the risk factors influencing the postoperative re-currence of cervical intraepithelial neoplasia after cervical conization.The receiver operating characteristic(ROC)curve was drawn to analyze the value of TGF-β1,CBX7 and suPAR in predicting the postoperative re-currence of cervical intraepithelial neoplasia after cervical conization.A nomogram model for predicting the postoperative recurrence of cervical intraepithelial neoplasia after cervical conization was established using R software and verified both internally and externally.The calibration curve and decision curve were used to ana-lyze the calibration ability and application value of the nomogram.Results The levels of TGF-β1,CBX7 and suPAR in the recurrence group were all higher than those in the non-recurrence group,and the difference was statistically significant(P<0.05).The results of multivariate Logistic analysis showed that TGF-β1,CBX7,and suPAR were all risk factors for postoperative recurrence of cervical intraepithelial neoplasia after cervical conization(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of the combined prediction of TGF-β1,CBX7,and suPAR for the postoperative recurrence of cervical intraepithelial neoplasia after cervical conization was higher than AUC of the individual detection of each index(Z=3.554,2.311,2.520,P<0.05).The correction curve of the nomogram model for predicting the postoperative recur-rence of cervical intraepithelial neoplasia after cervical conization approached the ideal curve(P=0.298,0.687).Conclusion The combination of TGF-β1,CBX7 and suPAR has certain value in predicting the postoperative recurrence of cervical intraepithelial neoplasia after cervical conization.
5.Effects of continuous positive airway pressure on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome
Zelin TU ; Rui BAI ; Linyan ZHANG ; Jingyu WANG ; Shenda HONG ; Jingjing YANG ; Jun WEI ; Yan WANG ; Yanan LIU ; Xiaosong DONG ; Fang HAN ; Guoli LIU
Chinese Journal of Obstetrics and Gynecology 2025;60(3):171-176
Objective:To analyze the effect of continuous positive airway pressure (CPAP) on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome (OSAS), especially on the incidence of hypertensive disorder in pregnancy (HDP) in women with moderate to severe OSAS.Methods:A total of 180 pregnant women with OSAS who were diagnosed through sleep monitoring during pregnancy due to high-risk factors of OSAS and registered in Peking University People′s Hospital from January 2021 to May 2024 were selected as the study subjects. Clinical data were collected from medical records for retrospective analysis. According to whether they received standardized treatment with CPAP, they were divided into the CPAP treatment group (42 cases) and the control group (138 cases). The CPAP treatment group consisted of 9 pregnant women with moderate to severe OSAS, while the control group consisted of 34 pregnant women with moderate to severe OSAS. The maternal and neonatal outcomes, the incidence of HDP, placental weight after delivery and placental weight/neonatal birth weight ratio were compared between the two groups.Results:(1) The average gestational age of pregnant women in the CPAP treatment group was higher than that in the control group [(38.7±1.0) vs (38.0±1.4) weeks], the proportion of infants small for gestational age (SGA) in the CPAP treatment group was lower [0 (0/42) vs 12.3% (17/138)], and the birth weight of infants in the CPAP treatment group was bigger [(3 396±475) vs (3 082±710) g); the differences between the two groups were statistically significant (all P<0.05). There were no significant differences between the CPAP treatment group and the control group in terms of delivery mode, rates of postpartum hemorrhage and preterm birth, umbilical artery blood gas analysis pH<7.1, lactate≥6.0 mmol/L, base excess<-12.0 mmol/L and the incidence of gestational diabetes mellitus and HDP (all P>0.05). (2) The placental weight of the CPAP treatment group was significantly lower than that of the control group [(554.0±70.6) vs (615.7±119.1) g], the placental weight/newborn birth weight ratio of the CPAP treatment group was significantly lower than that of the control group (median: 0.17 vs 0.19), and the differences were statistically significant (all P<0.05). (3) The incidence of HDP in pregnant women with moderate to severe OSAS in the CPAP treatment group was lower than that in the control group [1/9 vs 61.8% (21/34)], and the difference was statistically significant ( P<0.05). Conclusions:CPAP treatment could prolong the gestational age in pregnant women with OSAS, reduce the incidence of SGA, increase the birth weight of infants, and reduce the incidence of HDP in pregnant women with moderate to severe OSAS, and is worth promoting in clinical practice. The improvement of neonatal outcomes by CPAP treatment is closely related to the placenta, which is worthy of further exploration.
6.Advances in multi-source surveillance data integration and application of early warning indicators for respiratory infectious diseases
Dazhu HUO ; Ting ZHANG ; Jinzhao CUI ; Xiaochen ZHANG ; Yongtao CHI ; Yanan WANG ; Zhe WANG ; Xin ZHAO ; Ziliang FAN ; Chuchu YE ; Chuangsen FANG ; Yanming LI ; Zhongjie LI ; Weizhong YANG ; Chen WANG
Chinese Journal of Preventive Medicine 2025;59(8):1311-1319
The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.
7.A case diagnosed as highly virulent and highly resistant Campylobacter jejuni ST7268 bloodstream infection
Fang WANG ; Fen GAO ; Yue LIU ; Yanan WANG ; Xuebin XU
Chinese Journal of Laboratory Medicine 2025;48(1):149-152
A 51-year-old female patient was admitted to the hospital due to abdominal pain, vomiting, and fever lasting for one day. The clinical diagnosis was acute pelvic inflammatory disease and adenomyosis. Empirical treatment with cefoperazone/sulbactam sodium was given. Six days later, the blood culture reported Campylobacter jejuni ( C. jejuni), and nine days later, the patient was discharged with negative blood culture. The strain was identified as C. jejuni by morphology and matrix-assisted laser de-sorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Whole-genome sequencing predicted that the multi-locus sequence type was ST7268 (ST464 complex), which was a new invasive clone of foodborne C. jejuni with typical molecular characteristics of high vitality, high virulence and high resistance.
8.Mechanism of cerebroprotein hydrolysate-1 improving cognitive impairment in vascular dementia rats
Qinying MA ; Lixuan LI ; Yanan REN ; Bing LI ; Huimin SHI ; Jiyu FANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(9):1257-1262
Objective To explore the molecular mechanism of cerebroprotein hydrolysate-1(CH-1)in improving cognitive impairment of VD at animal level,and to determine the regulatory effect of CH-1 on Nrf2/ARE signaling pathway.Methods Thirty-six SD rats were randomly divided into sham operation group,VD group,low-and high-dose groups,with 9 rats in each group.VD model was established by bilateral common carotid artery ligation,and CH-1 was injected intraperitone-ally for 3 weeks.Morris water maze test and new object recognition test were performed to evalu-ate cognitive function.Hippocampal tissues was collected for immunohistochemistry/Western blot analysis.Results Compared with the sham operation group,the VD group exhibited significantly prolonged escape latency at 2-4 d of Morris water maze test,and up-regulated expression of ubiquitinated protein,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 protein in the hippocampus,while down-regulated P62 expression(P<0.05).Obviously shortened escape latency was observed in the high-dose group at 3-4 d and the low-dose group at 4 d than the VD group(P<0.05).The resi-dence time in target quadrant,number of platform crossings,total exploration time of novel object recognition in the high-dose group and the total exploration time of novel object recognition in the low-dose group were significantly longer than those in VD group(P<0.05).The expression levels of ubiquitinated,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 were significantly lower in the low-dose group and high-dose group than the VD group(P<0.05).The expression level of P62 protein in the VD group,low-and high-dose group were significantly increased in a dose-dependent manner(2.78±0.44,1.80±0.24 vs 3.67±0.34;2.37±0.26,1.53±0.09 vs 2.92±0.19;2.74±0.14,1.81±0.19 vs 3.93±0.50;2.28±0.17,1.72±0.17 vs 3.17±0.31,P<0.05).Conclusion CH-1 can effectively improve the cognitive ability of VD rats and reduce the autophagy of hippocampal neurons.This therapeutic effect may be closely related to its enhancing activity of Nrf2/ARE signaling pathway.
9.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
10.Explore the Formation and Treatment of Malignant Tumors from the Perspective of Yang Being Solid and Able to Hold on
Liguang FANG ; Dandan GAO ; Tong WANG ; Yanan ZHANG ; Shijun WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(5):576-581
Yang being solid is an important summary of the normal functional state of yang qi in The Yellow Emperor's Inner Classic.Based on the theory of yang being solid and able to hold on,it is proposed that yang being solid is essential to maintain the state of tightness,thoroughness and quietness for maintaining the health of the human body.Yang losing its solidity is the core patho-genesis of the onset and progression of malignant tumors,which manifests as yang deficiency,yang depression and yang restlessness.If yang is not solid due to its deficiency,yang will lose its warmth and defense and the evil qi will be retained;if yang is not solid due to its depression,yang will lose its warmth and circulation and phlegm and stasis will gather;if yang is not solid due to its restlessness,yang will lose its tranquility,burn yin and consume essence.Aiming at the core pathogenesis of yang losing its solidity,the treatment methods of warming yang and replenishing qi to treat the disease before it occurs,unblocking yang and removing turbidity to disperse the staleness,and clearing and resolving restless yang to fight cancer and detoxify are used in clinical practice.Restoring the solidity of yang is taken as the goal of treating malignant tumors,which provides ideas for the clinical practice of treating malignant tumors with traditional Chinese medicine.

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