1.Mechanism Study of Yinchenhao Tang Regulating Fas/Caspase-8/Caspase-3 Signaling Pathway to Improve Cholestatic Liver Injury
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Linjing SHE ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):39-46
ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 (Fas)/cysteine protease-8 (Caspase-8)/cysteine protease-3 (Caspase-3) signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury (CLI). MethodsAmong 48 Wistar rats,12 rats were randomly selected as the blank group,and the other rats were administered alpha-naphthalene isothiocyanate (ANIT) by gavage to induce a CLI model. The modeling rats were randomly divided into the model group, the ursodeoxycholic acid group(0.1 g·kg-1) and the Yinchenhao Tang group(9.23 g·kg-1),with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma-glutamyl transpeptidase (γ-GT),total bilirubin (TBil) and total bile acid (TBA) in serum were detected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3,B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with those in the blank group,the levels of ALT,AST,ALP,γ-GT,TBA and TBil in serum of the model group were significantly increased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased (P<0.01). The arrangement of hepatocytes was disordered,and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly increased(P<0.05,P<0.01),while the protein and mRNA expressions of Bcl-2 were significantly decreased (P<0.05,P<0.01). Compared with those in the model group,the levels of ALP,γ-GT,TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased(P<0.05,P<0.01). The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the mRNA expression of Bcl-2 was significantly increased (P<0.05,). The levels of ALT,AST,γ-GT,TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased (P<0.05,P<0.01). The protein expression of Fas and Bax and the mRNA expression of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the protein and mRNA expression of Bcl-2 were significantly increased (P<0.05,P<0.01). Hepatocyte injury,inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI,and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.
2.Mechanism of Yinchenhao Tang in Improving Cholestatic Liver Injury by Inhibiting TLR4/MyD88/NF-κB Signaling Pathway Through FXR
Zhengwang ZHU ; Yang YANG ; Jinghan ZHAO ; Linlin WANG ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):47-54
ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury (CLI) by inhibiting toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) pathway via regulating farnesol X receptor (FXR). MethodsA total of 40 Wistar male rats were randomly selected, with 10 as a blank group,and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate (ANIT). After modeling,they were randomly divided into the model group, the ursodeoxycholic acid (0.1 g·kg-1) group and the Yinchenhao Tang (9.23 g·kg-1) group,with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),γ-glutamyl transpeptidase (γ-GT),total bile acid (TBA),total bilirubin (TBil) and direct bilirubin (DBil) levels in serum were detected. Tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),and interleukin-6 (IL-6) levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR,TLR4,MyD88,NF-κB,F4/80,TNF-α,IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR,TLR4,MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. ResultsCompared with those in the blank group,ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the model group were significantly increased (P<0.01). The levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were significantly increased (P<0.01),and the mRNA and protein expressions of FXR in liver tissue were decreased (P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased (P<0.05,P<0.01). Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group,ALT,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.05,P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased (P<0.05,P<0.01). ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.01). The mRNA and protein expressions of FXR in liver tissue were significantly increased,and the mRNA expressions of TLR4,MyD88,NF-κB,and F4/80, as well as the protein expressions of TLR4 and NF-κB were obviously decreased (P<0.05,P<0.01). The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI,and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.
3.Effect of MOTS-c on hepatocyte injury induced by glycochenodeoxycholic acid by regulating transporter MRP2 expression
Yu AO ; Xuyang ZHANG ; Dan TANG ; Gongwei LIU ; Dan HUANG ; Zhifang CAI
Organ Transplantation 2025;16(3):425-434
Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.
4.Association between sleep characteristics, physical activity patterns with depressive and anxiety symptoms in college students
Chinese Journal of School Health 2025;46(4):552-557
Objective:
To explore the relationship between sleep characteristics, physical activity patterns, with depressive and anxiety symptoms in college students, so as to provide reference for student mental health promotion.
Methods:
From September to November 2023, a convenience sampling method was used to select 7 954 college students aged 18-22 years from 9 universities in Shanghai, Hubei, and Jiangxi. Assessments were conducted using the International Physical Activity Questionnaire Short-Form (IPAQ-SF), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI) to evaluate physical activity, depressive and anxiety symptoms, and sleep quality, respectively. Logistic regression analysis was employed to explore the impact of sleep characteristics and physical activity patterns on depressive and anxiety symptoms and their comorbidity among college students.
Results:
The detection rates for depressive symptoms, anxiety symptoms, and comorbid depression and anxiety symptoms were 25.67%, 35.39%, and 23.15%, respectively. Factors such as gender, grade, household registration, parental education level, annual family income, family structure, and dietary habits were all associated with the detection rates of depressive and anxiety symptoms and their comorbidity (χ2=4.41-118.39, P<0.05). Physical activity patterns, sleep duration, sleep quality, and sleepwake characteristics were also associated with the occurrence of depressive and anxiety symptoms and their comorbidity (χ2=9.66-627.70, P<0.05). Logistic regression analysis showed that college students who stayed up late and slept less than 7 had the highest risk of depressive and anxiety symptoms and their comorbidity (OR=1.93, 1.85, 1.88, P<0.05). Compared to regular physical activity patterns, insufficient physical activity patterns were associated with an increased risk of depressive and anxiety symptoms (all OR=1.18, P<0.05). Further stratified analysis results showed that the risk of depression, anxiety and their comorbidity increased in college students who stayed up late and slept less than 7 h, went to bed before midnight and slept less than 7 h, or went to bed before midnight and slept more than 7 h but did not have sufficient physical activity (P<0.05).
Conclusions
Sleep characteristics and physical activity patterns significantly affect depressive and anxiety symptoms in college students. Universities should strengthen sleep management and implement flexible physical activity interventions to help students establish healthy lifestyles.
5.A finite element analysis of different bone cement injection volumes and distribution patterns in bilateral percutaneous vertebral augmentation
Xiong BAO ; Xiao WU ; Xijie TANG ; Yougao ZHANG ; Jinkui CAI ; Zhanghua LI
Chinese Journal of Tissue Engineering Research 2025;29(10):2006-2014
BACKGROUND:The authors found that when the bilateral percutaneous vertebral augmentation is used to treat osteoporotic vertebral compression fractures with a total bone cement injection of 4 mL or more,different distribution patterns were usually presented on the X-rays;however,there were few reports addressing the effects of these patterns of bone cement distribution on the biomechanical properties of fractural vertebrae. OBJECTIVE:To further explore the biomechanical effects of different bone cement filling doses and distribution patterns on biomechanics of the fractural vertebrae using the finite element method. METHODS:The L1-L3 finite element models of osteoporosis were established,and the vertebral compression fractures were simulated in L2.Four distribution patterns bilateral partial fusion(FH type),full fusion(FO type),symmetrical separation(SA type),and asymmetric segregation(SN type)were simulated in 4 and 6 mL injections in the osteoporotic vertebral compression fracture models,respectively,and a total of nine sets of models were obtained.These models were solved under the same boundary conditions and compared with the stress and displacement of the L2 fractural vertebra. RESULTS AND CONCLUSION:(1)The maximum stresses of the nine groups of models were concentrated in the L2 fractural area,and the maximum stress and maximum displacement of each filling model were lower than in the osteoporotic vertebral compression fracture model,indicating the effectiveness of bone cement filling in the treatment of osteoporotic vertebral compression fracture.(2)Compared with 4 mL bone cement filling,6 mL bone cement filling could significantly reduce the stress of fractured vertebrae and enhance the strength of fractured vertebrae while improving the stability of fractured vertebrae.(3)In the same state of movement,the FH type stress was the least,followed by the SA type,both of which were close.FO type stress was the largest,especially in the lateral bend,which might be associated with its cluster shape resulting in the concentration of lateral stress.In the aspect of displacement,FH type was the least and FO type was the largest.(4)The results show that increased dose of bone cement injection reduces fractural vertebral stress and improves stability,but increases the risk of leakage.Bilateral symmetrical dispersed bone cement(FH type,SA type)is superior in restoring vertebral strength and stability than full fusion(FO type),asymmetric separated(SN type)bone cement.Therefore,when clinically performing bilateral percutaneous vertebral augmentation treatment of osteoporotic vertebral compression fractures,the bilateral symmetric dispersions of the distribution are first guaranteed;priority is recommended for FH type distribution,for appropriate stress stimulation and best stability.
6.Textual Research on Key Information of Famous Classical Formula Jiegengtang
Yang LEI ; Yuli LI ; Xiaoming XIE ; Zhen LIU ; Shanghua ZHANG ; Tieru CAI ; Ying TAN ; Weiqiang ZHOU ; Zhaoxu YI ; Yun TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):182-190
Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics, this study conducted a textual research and analysis on the key information such as formula origin, decocting methods, and clinical application of Jiegengtang. After the research, it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease, which is also known as Ganjietang, and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear, Jiegeng is the dried roots of Platycodon grandiflorum, Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis, the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix, decocted with 600 mL of water to 200 mL, taken warmly after meals, twice a day, 100 mL for each time. In ancient times, Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome, with cough and sore throat as its core symptoms. In modern clinical practice, Jiegengtang is mainly used for respiratory diseases such as pharyngitis, esophagitis, tonsillitis and lung abscess, especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.
7.Textual Research on Key Information of Famous Classical Formula Jiegengtang
Yang LEI ; Yuli LI ; Xiaoming XIE ; Zhen LIU ; Shanghua ZHANG ; Tieru CAI ; Ying TAN ; Weiqiang ZHOU ; Zhaoxu YI ; Yun TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):182-190
Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics, this study conducted a textual research and analysis on the key information such as formula origin, decocting methods, and clinical application of Jiegengtang. After the research, it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease, which is also known as Ganjietang, and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear, Jiegeng is the dried roots of Platycodon grandiflorum, Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis, the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix, decocted with 600 mL of water to 200 mL, taken warmly after meals, twice a day, 100 mL for each time. In ancient times, Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome, with cough and sore throat as its core symptoms. In modern clinical practice, Jiegengtang is mainly used for respiratory diseases such as pharyngitis, esophagitis, tonsillitis and lung abscess, especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.
8.Safety analysis of Yttrium-90 resin microsphere selective internal radiation therapy on malignant liver tumors
Jia CAI ; Shiwei TANG ; Rongli LI ; Mingxin KONG ; Hongyan DING ; Xiaofeng YUAN ; Yuying HU ; Ruimei LIU ; Xiaoyan ZHU ; Wenjun LI ; Haibin ZHANG ; Guanwu WANG
Chinese Journal of Clinical Medicine 2025;32(1):24-29
Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (90Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent 90Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of 90Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (99mTc-MAA) perfusion test and received the 90Y-SIRT; one patient received 90Y-SIRT after the second 99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of 90Y-SIRT for treating malignant liver tumors are mild, indicating good safety.
9.Research progress of meibomian gland dysfunction-related dry eye
Jianbo ZHONG ; Guoqiang ZENG ; Yi ZHANG ; Xiaoyan DOU ; Wanmei TANG ; Kunling CHEN ; Li CAI
International Eye Science 2025;25(2):259-263
In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.
10.Mechanism of Shengmai Injection Against Cerebral Ischemia Based on Proteomics
Jingtong LIU ; Shaowei HU ; Mengli CHANG ; Jing XU ; Qingqing CAI ; Xinghong LI ; Liying TANG ; Huanhuan WANG ; Hongwei WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):57-67
ObjectiveTo evaluate pharmacological effects of Shengmai injection(SMI)on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly divided into a sham group, a model group, a low-dose SMI group(3 mL·kg-1), a middle-dose SMI group(6 mL·kg-1), a high-dose SMI group(12 mL·kg-1), and a Ginaton group(4 mL·kg-1)according to the random number table method, with 12 rats in each group. The rat model of cerebral ischemia-reperfusion(MCAO/R)was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion, which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores, cerebral infarction area, hematoxylin-eosin (HE) staining, Nissl staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay (ELISA), Western blot, and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation(OGD/R)-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group, the model group showed significantly increased neurological function scores, cerebral infarction area, neuronal apoptosis rate, and expression levels of apoptosis related proteins (P<0.05, P<0.01)and significantly decreased density of Nissl bodies and neurons(P<0.01). Compared with the model group, the SMI groups exhibited significantly decreased neurological function scores, cerebral infarction area, neuronal apoptosis rate, and expression levels of apoptosis related proteins (P<0.05, P<0.01)and significantly increased density of Nissl bodies and neurons (P<0.05). The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury, and the chloride intracellular channel protein 1 (CLIC1) was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced, compared with those in the model group(P<0.05, P<0.01), and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 (NLRP3) decreased (P<0.01). In addition, the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate(P<0.01) and significantly decreased the intracellular chloride ion concentration(P<0.05). ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.


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