1.Cigu Xiaozhi Prescription Alleviates NASH Liver Fibrosis by Inhibiting the Activation of the Hedgehog Signaling Pathway
Zhen REN ; Yongjia YANG ; Cai GUO ; Yujie ZHANG ; Yanhua MA
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(7):936-945
OBJECTIVE To explore the potential mechanism of Cigu Xiaozhi Prescription(CGXP)in the treatment of non-alco-holic steatohepatitis(NASH)liver fibrosis.METHODS A NASH mouse model was established.The degree of liver enlargement was evaluated by calculating the liver index.Hematoxylin-eosin(HE)and Masson staining were used to observe the degree of liver fibro-sis.In addition,immunohistochemistry was employed to detect the expression of liver fibrosis-related proteins,including α-SMA,Collagen 1,MMP2,and MMP9.Western blot and qPCR techniques were used to detect the expression levels of HIF-1α,E-cadher-in,N-cadherin,Shh,Smo,Gli1,and Gli2 in the mouse liver.The alkaline hydrolysis method was used to measure the content of liv-er hydroxyproline.RESULTS CGXP could effectively reduce the liver index(P<0.001),alleviate liver enlargement and inflamma-tion,and significantly improve the pathological damage of liver tissue in mice with liver fibrosis.CGXP significantly decreased the ex-pression levels of liver fibrosis-related proteins α-SMA,Collagen 1,MMP2 and MMP9(P<0.01,P<0.000 1);reduced the levels of HIF-1α,E-cadherin,N-cadherin,Shh,Smo,Gli1,and Gli2,and the therapeutic effect of high-dose CGXP was particularly significant(P<0.05,P<0.01,P<0.001,P<0.000 1).CONCLUSION CGXP can relieve NASH liver fibrosis in mice by reducing the liver index,alleviating inflammation,and improving tissue pathological damage.The mechanism may be related to the inhibition of the Hedgehog signaling pathway,which alters the activation and proliferation of hepatic stellate cells and reduces the synthesis and dep-osition of extracellular matrix.
2.Construction and Validation of a Risk Prediction Model for Postoperative Constipation in Patients With Osteoporotic Thoracolumbar Fracture Undergoing Percutaneous Kyphoplasty
Xiaofeng LIU ; Yanhua WU ; Lin KANG ; Shuhui LIN ; Ziming CAI ; Wenping LIN
Journal of Sichuan University (Medical Sciences) 2025;56(5):1305-1312
Objective To develop an instrument for predicting postoperative constipation risks in patients with osteoporotic thoracolumbar fracture(OTLF)who have undergone percutaneous kyphoplasty(PKP).Methods A total of 858 OTLF patients who underwent PKP surgery between January 2020 and December 2024 were enrolled.The patients were randomly assigned to a training set(n=600)and a validation set(n=258)in a 7∶3 ratio.According to whether the patients had postoperative constipation,the training set was divided into a constipation group(n=205)and a non-constipation group(n=395),and the validation set was divided into a constipation group(n=90)and a non-constipation group(n=168).Logistic regression analysis was conducted to analyze the factors influencing postoperative constipation in OTLF patients after PKP,and a nomogram model was constructed accordingly.The receiver operating characteristic(ROC)curve and the calibration curve of the model were plotted,and the Hosmer-Lemeshow test for goodness of fit was performed.Results A total of 205 OTLF patients(34.17%)in the training set and 90 OTLF patients(34.88%)in the validation set experienced constipation after PKP.Univariate analysis revealed significant differences between the constipation and non-constipation groups in terms of operative time,postoperative water intake,time to first postoperative meal,postoperative bed rest time,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the Nutrition Risk Screening 2002(NRS-2002)score,and the levels of sodium,potassium,and HbA1c(P<0.05).Least absolute shrinkage and selection operator(LASSO)regression was performed and operative time,time to first postoperative meal,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the NRS-2002 score,and the levels of sodium,potassium,and HbA1c were identified as candidate predictors.Multivariate logistic analysis showed that the time to first postoperative meal,the levels of Bifidobacterium and Lactobacillus,the NRS-2002 score,and the levels of sodium and HbA1c were influencing factors of postoperative constipation in OTLF patients(P<0.05).The ROC curves showed that the area under the curve(AUC)of the training set was 0.842(95%CI:0.793-0.892),while that of the validation set was 0.860(95%CI:0.830-0.889).The calibration curves demonstrated good agreement between the prediction curve and the standard curve in both the training set and the validation set.Conclusion The time to the first postoperative meal,the NRS2002 score,and the levels of Bifidobacterium,Lactobacillus,sodium,and HbA1c are influencing factors of post-PKP constipation in OTLF patients.The nomogram model built based on these factors exhibited good predictive performance.
3.Analysis of clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry
Jianing GU ; Dongmei XU ; Jing SHAO ; Jing GAO ; Zhuang CAI ; Yanhua QU ; Xiaolu YE ; Mengqian ZHANG ; Dongli MEI ; Yanhong ZHANG ; Bo YANG ; Gen CHENG ; Lina WANG ; Junrong YE ; Ruiyue LIN ; Yongling ZHOU ; Runjuan MA
Chinese Journal of Nursing 2025;60(11):1359-1365
Objective To understand the clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry,and to provide references for promoting the standardized practice of psychiatric protective restraints and updating the consensus.Methods By the convenience sampling method,a questionnaire survey was conducted among nurses from 480 hospitals in 30 provinces from June 15 to July 15,2024.The survey was conducted using the instrument for evaluating clinical applicability of guide-lines(version 2.0)and a self-compiled questionnaire on the clinical implementation of the restraint consensus.Results A total of 7,844 valid questionnaires were collected,with a valid questionnaire recovery rate of 93.78%.The results of clinical applicability scoring showed that the consensus had the lowest availability score(64.72%)and the highest acceptability score(76.74%).The results showed that nurses' receiving training and the level of their hospitals were the main influencing factors for scores in various dimensions(P<0.05).4,774 participants(87.42%)believed that the application of consensus could enhance the standardization of nurses' restraint operations.The safety rate of the restraint consensus was 79.51%,and the economic ratio was 76.87%.Among the evaluators,1,739(22.17%)believed that there were implementation obstacles in the consensus.Conclusion The clinical applicability of the consensus is relatively good,and the application of the consensus helps to improve the standardization of clinical operations.In the future,efforts should be made to strengthen the promotion and training of the consensus,develop hierarchical promotion strategies according to the characteristics of medical institutions,and improve the quality of evidence for the consensus,so as to further enhance the clinical application effect of the consensus.
4.Cigu Xiaozhi Prescription Alleviates NASH Liver Fibrosis by Inhibiting the Activation of the Hedgehog Signaling Pathway
Zhen REN ; Yongjia YANG ; Cai GUO ; Yujie ZHANG ; Yanhua MA
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(7):936-945
OBJECTIVE To explore the potential mechanism of Cigu Xiaozhi Prescription(CGXP)in the treatment of non-alco-holic steatohepatitis(NASH)liver fibrosis.METHODS A NASH mouse model was established.The degree of liver enlargement was evaluated by calculating the liver index.Hematoxylin-eosin(HE)and Masson staining were used to observe the degree of liver fibro-sis.In addition,immunohistochemistry was employed to detect the expression of liver fibrosis-related proteins,including α-SMA,Collagen 1,MMP2,and MMP9.Western blot and qPCR techniques were used to detect the expression levels of HIF-1α,E-cadher-in,N-cadherin,Shh,Smo,Gli1,and Gli2 in the mouse liver.The alkaline hydrolysis method was used to measure the content of liv-er hydroxyproline.RESULTS CGXP could effectively reduce the liver index(P<0.001),alleviate liver enlargement and inflamma-tion,and significantly improve the pathological damage of liver tissue in mice with liver fibrosis.CGXP significantly decreased the ex-pression levels of liver fibrosis-related proteins α-SMA,Collagen 1,MMP2 and MMP9(P<0.01,P<0.000 1);reduced the levels of HIF-1α,E-cadherin,N-cadherin,Shh,Smo,Gli1,and Gli2,and the therapeutic effect of high-dose CGXP was particularly significant(P<0.05,P<0.01,P<0.001,P<0.000 1).CONCLUSION CGXP can relieve NASH liver fibrosis in mice by reducing the liver index,alleviating inflammation,and improving tissue pathological damage.The mechanism may be related to the inhibition of the Hedgehog signaling pathway,which alters the activation and proliferation of hepatic stellate cells and reduces the synthesis and dep-osition of extracellular matrix.
5.Analysis of clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry
Jianing GU ; Dongmei XU ; Jing SHAO ; Jing GAO ; Zhuang CAI ; Yanhua QU ; Xiaolu YE ; Mengqian ZHANG ; Dongli MEI ; Yanhong ZHANG ; Bo YANG ; Gen CHENG ; Lina WANG ; Junrong YE ; Ruiyue LIN ; Yongling ZHOU ; Runjuan MA
Chinese Journal of Nursing 2025;60(11):1359-1365
Objective To understand the clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry,and to provide references for promoting the standardized practice of psychiatric protective restraints and updating the consensus.Methods By the convenience sampling method,a questionnaire survey was conducted among nurses from 480 hospitals in 30 provinces from June 15 to July 15,2024.The survey was conducted using the instrument for evaluating clinical applicability of guide-lines(version 2.0)and a self-compiled questionnaire on the clinical implementation of the restraint consensus.Results A total of 7,844 valid questionnaires were collected,with a valid questionnaire recovery rate of 93.78%.The results of clinical applicability scoring showed that the consensus had the lowest availability score(64.72%)and the highest acceptability score(76.74%).The results showed that nurses' receiving training and the level of their hospitals were the main influencing factors for scores in various dimensions(P<0.05).4,774 participants(87.42%)believed that the application of consensus could enhance the standardization of nurses' restraint operations.The safety rate of the restraint consensus was 79.51%,and the economic ratio was 76.87%.Among the evaluators,1,739(22.17%)believed that there were implementation obstacles in the consensus.Conclusion The clinical applicability of the consensus is relatively good,and the application of the consensus helps to improve the standardization of clinical operations.In the future,efforts should be made to strengthen the promotion and training of the consensus,develop hierarchical promotion strategies according to the characteristics of medical institutions,and improve the quality of evidence for the consensus,so as to further enhance the clinical application effect of the consensus.
6.Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis
Jialin YANG ; Bingjie CAI ; Yuhao DAI ; Shuting LI ; Keke ZHANG ; Yanhua GAO ; Qiman ZHANG ; Ying ZHANG ; Jianying SHEN ; Shaojing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):91-100
ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula (YQ) in treating ischemic stroke (IS) from the perspective of the microbial-gut-brain axis (MGBA). MethodRats were randomly divided into five groups, with six in each group, including sham surgery group, model group, and low, medium, and high dose YQ groups (1, 5, and 25 mg·kg-1). Except for the sham surgery group, all other groups were established with a middle cerebral artery occlusion (MCAO) model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring, and the protective effect of YQ on IS was evaluated. Then, the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology, and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 (IL-6), interleukin-17A (IL-17A), and interleukin-10 (IL-10) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue, and hematoxylin-eosin staining (HE) was used to observe pathological changes in the cerebral cortex and colon, so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats (P<0.01) and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them, significantly changed microorganisms include Morgentia, Escherichia Shigella, Adlercreutzia, and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group, the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A (P<0.01) and a decrease in the content of anti-inflammatory factor IL-10 (P<0.01). Compared with the model group, the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased (P<0.05), and that of anti-inflammatory factor IL-10 increased (P<0.01). The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats (P<0.05), while the expression levels of both increased in the treatment group (P<0.05). ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier, and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia, inhibit systemic inflammatory response, and improve the disruption of the gut-blood brain barrier, preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.
7.Exploring Mechanism of Neferine in Promoting Vascular Regeneration Against Cerebral Ischemia Based on Mitochondrial MCU Channel
Qiman ZHANG ; Yanhua GAO ; Wenjie WU ; Wei YANG ; Chen LIU ; Shuting LI ; Bingjie CAI ; Jialin YANG ; Ying ZHANG ; Jing MA ; Shaojing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):103-113
ObjectiveTo investigate the mechanism of neferine(Nef) in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter(MCU) ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index, the vascular regenerative efficacy of Nef was evaluated, and the median effective concentration(EC50) was calculated. Rats were randomly divided into a sham operation group, a model group, a positive drug group(butylphthalide, 6 mg·kg-1), and Nef low, medium, and high dose groups(0.125, 0.625, 3.125 μg·kg-1). Except for the sham operation group, the middle cerebral artery occlusion(MCAO) model was established in other groups. After modeling, the groups were administered the corresponding dose of drugs by gavage, while the sham operation and model groups received equal volumes of saline, once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats, and the infarct rate of ischemic brain tissue was calculated by 2,3,5-triphenyltetrazolium chloride(TTC) staining. The regional cerebral blood flow(rCBF) of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor(VEGF), platelet endothelial cell adhesion molecule-1(CD31), and hypoxia-inducible factor-1α(HIF-1α) proteins in each group. Human umbilical vein endothelial cells(HUVECs) were divided into the normal group, model group, positive drug group(astragaloside Ⅳ, 10 μmol·L-1), and Nef group (32 nmol·L-1). In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration, the spermine(MCU agonist) and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation(OGD) was established in all groups except the normal group, the cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes(Rhod-2 AM, Fluo-3 AM, JC-1, Calcein AM) and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α, and Western blot was used to detect the effects of Nef on the protein expressions of MCU, B-cell lymphoma-2 associated X protein(Bax), Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group, the area of subintestinal vessels in the model group significantly decreased(P<0.01). Compared to the model group, different concentrations of Nef could significantly increase the area of subintestinal vessels(P<0.01), with the maximum tolerated concentration of 10.24 μmol·L-1 and the EC50 of 0.23 μmol·L-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group, the model group had a significant decrease in rCBF and a significant increase in infarct rate, while CD31 expression significantly decreased(P<0.01), and VEGF and HIF-1α protein expressions significantly increased(P<0.05). Compared to the model group, the treated groups showed significant increases in rCBF, significant reductions in infarct volume, and significant increases in CD31, VEGF, and HIF-1α protein expression(P<0.01). Cell experiment results showed that compared to the normal group, the model group had decreased cell viability and migration ability, increased intracellular Ca2+ and mitochondrial Ca2+ levels, reduced mitochondrial permeability transition pore(MPTP) opening, and decreased mitochondrial energy metabolism capability, with increased expressions of MCU, Bax, Caspase-3 and HIF-1α proteins(P<0.05, P<0.01). Compared to the model group, the Nef group showed increased cell viability and migration ability, decreased intracellular Ca2+ and mitochondrial Ca2+ levels, increased MPTP opening, enhanced mitochondrial energy metabolism capability, decreased expressions of MCU, Bax and Caspase-3 proteins, and increased HIF-1α protein expression(P<0.05, P<0.01). ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU, it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway, enhancing the expression of VEGF and CD31, thereby promoting vascular regeneration to treat ischemic brain injury.
8.Chinese Medicine Regulates Hepatocellular Carcinoma-related Signaling Pathways: A Review
Chun YU ; Fen GAO ; Lanlan ZHENG ; Cai GUO ; Yanfang HE ; Jiaojiao XIE ; Xuan ZHANG ; Yanhua MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):232-243
Hepatocellular carcinoma (HCC) is a common tumor in the digestive tract, the formation mechanism of which remains to be fully elucidated. Although surgery, radiation, chemotherapy, targeted therapy, and immunotherapy have achieved significant results in the treatment of HCC, these methods are accompanied by a considerable number of adverse reactions and complications. In recent years, Chinese medicine has shown remarkable efficacy in the treatment of HCC, and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine, which exerts therapeutic effects via multiple components and multiple targets. However, the pathogenesis of HCC is exceptionally complex and not fully understood, which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Hedgehog, Wnt/β-catenin, nuclear factor-κB (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and transforming growth factor-β (TGF-β)/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis, inhibiting cell proliferation and migration, and blocking the cell cycle via the above pathways. However, the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets, new perspectives, and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.
9.Application of B-ultrasound-guided transabdominal villus and amniocentesis in prenatal diagnosis of thalassemia
Lanlan ZHANG ; Fenfang HUANG ; Feifei GONG ; Haiyan CAI ; Xuemei HU ; Yanhua HUANG ; Pei LIANG ; Yijuan CHEN
China Modern Doctor 2024;62(3):13-15
Objective To explore the clinical application of ultrasound-guided transabdominal villus and amniocentesis in the prenatal diagnosis of thalassemia,and to find a suitable method for the prenatal diagnosis of thalassemia in Qinzhou.Methods A total of 531 high-risk pregnant women with severe or intermediate thalassemia during single pregnancy who were treated in the Department of Medical Genetics and Prenatal Diagnosis,Qinzhou Maternal and Child Health Hospital from March 2021 to April 2022 were selected for the study.According to different sampling methods,they were divided into control group(amniocentesis,n=415)and study group(transabdominal villus puncture,n=116).The success rate,complication rate of the two groups were compared.Results The success rate of puncture in the control group was 100%,2 cases were aborted within 2 weeks after surgery,17 cases were diagnosed with severe alpha-thalassemia,10 cases with severe β-thalassemia and 64 cases with intermediate thalassemia,48 cases with moderate and severe thalassemia induced labor.The success rate of puncture in the research group was 100%,10 cases were diagnosed with severe alpha-thalassemia,4 cases with severe β-thalassemia and 17 cases with intermediate thalassemia,and 26 cases with moderate severe thalassemia were induced labor.There was no significant difference in puncture success rate and abortion rate between the two methods(P>0.05).Conclusion Both methods are safe and effective.Transabdominal villus sampling can detect fetal thalassemia in early pregnancy,and it is worth promoting and applying in clinical practice.
10.Effects of protein powder on the bioavailability of perfluoroalkyl substances in rat kidney
CAI Delei ; ZHENG Yibin ; XIA Yong ; ZHANG Shixin ; SONG Yanhua ; SHEN Haitao ; YAO Jin ; CHEN Qing
Journal of Preventive Medicine 2024;36(3):268-271
Objective:
To explore the effects of protein powder on the bioavailability of perfluoroalkyl substances (PFASs) in blood and kidneys of rats and renal function change.
Methods:
Twenty-four rats of the SD strain were randomly divided into the negative control group, PFASs group and protein powder group, with 8 rats (half males and half females) in each group. PFASs included 13 perfluorocarboxylic acids (PFCAs) and 8 perfluorosulfonic acids (PFSAs), and the mixture was used as a test subject for intervention. The rats in the negative control group were given deionized water at doses of 20 mL/kg·bw, in the PFASs group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of deionized water, and in the protein powder group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of protein powder (0.258 g/mL). After intervention for 28 successive days, body weight and kidney mass were weighed, and the kidney volume index was calculated. Serum creatinine and blood urea nitrogen were detected by an automatic biochemical analyzer. The PFCAs, PFSAs and PFASs contents were quantified in blood and kidney using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry, and the bioavailability was estimated.
Results:
There was no significant differences in kidney mass, kidney volume index, serum creatinine and blood urea nitrogen among the negative control group, PFASs group and protein powder group (all P>0.05). The bioavailability of blood PFCAs, PFSAs and PFASs in the protein powder group was not significantly different from the PFASs group (all P>0.05). Compared with the PFASs group, the bioavailability of PFCAs, PFSAs and PFASs were significantly increased in kidneys of male rats in the protein powder group (all P<0.05), while were not significant different in those of female rats (all P>0.05).
Conclusion
Protein powder at the dose of this study can significantly improve the bioavailability of PFASs in kidneys of male rats, while there no obvious effects on the bioavailability of blood PFASs and renal function.


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