1.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
2.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
3.Analysis of sports supplement usage among grade 9 students and associated factors
GE Meiqin, CUI Yinchen, XUE Yaqi, BA Yi, CHEN Shuo, LAI Fengkun, ZHANG Hongyu, ZHEN Zhiping
Chinese Journal of School Health 2026;47(3):323-326
Objective:
To investigate the status and associated factors of sports supplement usage among grade 9 students, so as to provide a scientific basis for targeted supervision and health education regarding sports supplement usage among junior high school students.
Methods:
From June to September 2025, a stratified cluster random sampling method was used to select 2 261 grade 9 students from 10 provinces (autonomous regions, municipalities) in China. A questionnaire survey was conducted on their sports supplement usage and related factors. The Chi square test was used to compare the usage rates of sports supplements among different groups of students, and binary Logistic regression analysis was employed to investigate the related factors of sports supplement usage among grade 9 students.
Results:
Totally 59.7% of the grade 9 students used sports supplements. The usage rate (62.5%) was higher among boys than girls (56.3%), higher among students from rural areas and towns/counties (66.5%, 66.2%) than those from urban districts (52.9%), higher among boarding students (65.2%) than non resident students (54.3%), higher among students whose parents occupations were businessmen and workers (fathers: 65.0%, 63.7%; mothers: 63.6%, 61.1%) than those whose parents were farmers and civil servants (fathers: 57.5%, 54.1%; mothers: 58.8%, 55.7%), higher among students with a monthly family income of 5 000- 10 000 yuan (66.3%) than those in other income groups, and higher among students in the high score zone for the entrance physical examination to senior high school (67.7%) than those in the medium and low score zones ( 56.3% , 56.5%) ( χ 2=8.99, 42.21, 27.98, 20.55, 8.20, 22.74, 24.70, respectively, all P <0.05). Binary Logistic regression analysis showed that boys ( OR =1.26), those from rural areas ( OR =1.59), boarding students ( OR =1.36), those with a monthly family income of 5 000- 10 000 yuan ( OR =1.41), and those in the high score zone for entrance physical examination to senior high school ( OR =1.34) were more likely to use sports supplements during the entrance physical examination to senior high school; the probability of sports supplement usage was lower among students whose fathers were civil servants ( OR =0.74) (all P <0.05).
Conclusions
The usage of sports supplements is relatively common among grade 9 students. Intervention measures should be targeted at specific populations to reduce the risk of misuse.
5.P4HA1 mediates YAP hydroxylation and accelerates collagen synthesis in temozolomide-resistant glioblastoma.
Xueru LI ; Gangfeng YU ; Xiao ZHONG ; Jiacheng ZHONG ; Xiangyu CHEN ; Qinglong CHEN ; Jinjiang XUE ; Xi YANG ; Xinchun ZHANG ; Yao LING ; Yun XIU ; Yaqi DENG ; Hongda LI ; Wei MO ; Yong ZHU ; Ting ZHANG ; Liangjun QIAO ; Song CHEN ; Fanghui LU
Chinese Medical Journal 2025;138(16):1991-2005
BACKGROUND:
Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.
METHODS:
Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ.
RESULTS:
This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival.
CONCLUSION
P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide
;
Humans
;
Glioblastoma/drug therapy*
;
Animals
;
Mice
;
Cell Line, Tumor
;
Drug Resistance, Neoplasm/genetics*
;
YAP-Signaling Proteins
;
Hydroxylation
;
Dacarbazine/pharmacology*
;
Adaptor Proteins, Signal Transducing/metabolism*
;
Transcription Factors/metabolism*
;
Collagen/biosynthesis*
;
Collagen Type I/metabolism*
;
Prolyl Hydroxylases/metabolism*
;
Antineoplastic Agents, Alkylating/therapeutic use*
6.Depressive symptoms and associated factors among middle school and college students from 2021 to 2023 in Hunan Province
Chinese Journal of School Health 2025;46(1):96-101
Objective:
To investigate the current status and trends of depressive symptoms among middle school and college students in Hunan Province, and to explore the primary related factors of depressive symptoms, so as to provide a scientific basis for strengthening mental health among students.
Methods:
A total of 279 382 students in Hunan Province were selected through a stratified cluster random sampling method from 2021 to 2023. National Survey Questionnaire on Common Diseases and Health Influencing Factors among Students was adopted for the survey, and the Center for Epidemiological Studies Depression Scale was used to assess their depressive symptoms. The χ 2 test and trend χ 2 test were used to analyze depressive symptoms prevalence and trends, and multivariable Logistic regression was used to analyze the related factors of depressive symptoms.
Results:
The prevalence of depressive symptoms among students in Hunan Province from 2021 to 2023 were 19.66%, 20.17% and 21.47%, respectively, showing an upward trend ( χ 2 trend =9.07, P <0.01). In addition, the results of the multivariable Logistic regression analysis showed that students with healthy diet ( OR=0.43, 95%CI =0.40-0.45), adequate sleep ( OR=0.88, 95%CI =0.86-0.90), and acceptable screen time ( OR=0.61, 95%CI =0.60-0.62) had lower risks in depressive symptoms detection, while students with smoking ( OR= 1.95, 95%CI =1.88-2.02), secondhand smoke exposure ( OR=1.33, 95%CI =1.30-1.36) and Internet addiction ( OR= 4.19 , 95%CI =4.05-4.34) had higher risks in depressive symptoms detection, with differences in the degree of association among different genders, educational stages and urban rural groups ( OR=0.40-6.04, Z =-12.69-11.98) ( P <0.05).
Conclusions
There is an increasing trend of depressive symptoms among middle school and college students in Hunan Province from 2021 to 2023.Targeted depression prevention measures should be taken for students with different demographic characteristics to promote their mental health.
7.Consistent observation of cardiac output in severe patients monitored continuously by LiDCO and PiCCO
Yaqi XU ; Yongyi CHEN ; Dezhi REN ; Chen LI ; Jun DUAN
Journal of Chinese Physician 2025;27(3):373-376
Objective:To investigate whether continuous cardiac output (CO) parameters obtained by LiDCO in hemodynamic monitoring of severe patients are consistent with pulse index continuous cardiac output (PiCCO).Methods:From May 18, 2024 to January 10, 2025, 12 critically ill patients who were monitored by PiCCO in the Intensive Care Unit Department of China-Japan Friendship Hospital were prospectively collected. The PiCCO and LiDCO systems were simultaneously connected to the same critically ill patient, injected with ice saline for external calibration, and the average of paired continuous CO measurements were collected. Bland-Altman was used to analyze whether the two were consistent, and Spearman was used to analyze the correlation between norepinephrine dosage and bias.Results:In the data series of 70 pairs, the CO measured by PiCCO was 5.55±1.74, and the CO measured by LiDCO was 4.40(2.90, 6.50), with a bias of 0.52(95% CI: 0.07-0.96) and an upper limit of agreement of 4.2(95% CI: 3.4-4.9), the lower limit of the conformance limit was -3.1(95% CI: -3.9 to -2.4), and the percentage error was 66%, exceeding the clinically acceptable 45%. In the data series where norepinephrine was continuously pumped at the time of data collection, there was a moderate positive correlation between norepinephrine dosage and absolute bias ( r=0.47, P<0.05). There were statistically significant differences in absolute values of bias between groups defined as 0.5 μg/(kg·min) and 1 μg/(kg·min) ( P<0.05). Conclusions:There is no clinically acceptable consistency between LiDCO and PiCCO for continuous CO monitoring in severe patients, and the size of bias may be related to the dosage of norepinephrine.
8.Application of enhanced CT,energy spectrum CT and enhanced MR in evaluating hepatocellular carcinoma after TACE treatment
Zhichao CAO ; Huanyu CHEN ; Hong ZHANG ; Qianqian YANG ; Wuhao LI ; Yaqi WANG ; Kewu HE
Journal of Interventional Radiology 2025;34(9):971-976
Objective To assess the clinical value of conventional contrast enhanced CT(CECT),multi parameter energy spectrum CT,and contrast enhanced MR(CEMR)imaging methods in evaluating hepatocellular carcinoma(HCC)after TACE treatment.Methods The clinical data of 66 HCC patients,who underwent TACE treatment at authors' hospital and received CECT,multi parameter energy spectrum CT and CEMR in 1-3 months after treatment,were retrospectively analyzed.Taking DSA results as the gold standard,the recurrent or residual lesions detected by DSA were classified as positive lesions,while the lesions having no obvious recurrence or residues were classified as negative lesions.The positive lesions that were detected by both DSA and other imaging methods were regarded as true positive lesions.The accuracy,sensitivity,specificity,Kappa value were used to compare the values of CECT,multi parameter energy spectrum CT and CEMR in evaluating the positive/negative lesions of HCC after TACE treatment,and the number of detected lesions and accuracy rate were used to evaluate the values of the above imaging methods in demonstrating the iodine oil deposition status and in diagnosing true positive lesions.Results A total of 133 positive lesions and 35 negative lesions were detected by DSA.The accuracy of CEMR in diagnosing lesions was highest,the accuracy rate was 88.70%(both P<0.05);CEMR and energy spectrum CT had the highest diagnostic efficiency,the sensitivity for positive lesions was 92.31%and 81.95%respectively,and the difference between the two methods was not statistically significant(P>0.05).No statistically significant difference in the ability of diagnosing negative lesions existed between each other among the three groups(all P>0.05).The Kappa value suggested that the ability for diagnosing lesions after TACE treatment of CEMR was stronger than that of energy spectrum CT(Kappa value was 0.68 and 0.56 respectively,both P<0.05).CECT and multi parameter energy spectrum CT had the same accuracy in evaluating the iodine oil deposition status(both were 91.7%).No statistically significant difference in diagnosing even iodine oil deposition of the true positive lesions existed between each other among the three groups(all P>0.05).For diagnosing uneven iodine oil deposition of the true positive lesions,CEMR had the highest accuracy(92.50%,all P<0.05).Conclusion CEMR and multi parameter energy spectrum CT have more reliable diagnostic performance than conventional CECT,besides,CEMR has the highest diagnostic performance.However,multi parameter energy spectrum CT and CECT are the better choice for evaluating the deposition status of iodine oil.
9.Jianpi Yangzheng Xiaozheng Prescription inhibiting lung pre-metastatic niche formation of gastric cancer through reducing gastric cancer exosome PD-L1
Cancan ZHANG ; Yanzhen CHEN ; Xingxing ZHANG ; Wenjie LI ; Bo HAN ; Yaqi LI ; Jian WU ; Shenlin LIU
International Journal of Traditional Chinese Medicine 2025;47(6):798-806
Objective:To investigate the effects and mechanism of Jianpi Yangzheng Xiaozheng Prescription in lung pre-metastatic niche formation of gastric cancer by regulating the content of programmed death receptor ligand 1 (PD-L1) in gastric cancer exosomes.Methods:Totally 30 615 mice were divided into normal group, model group, Jianpi Yangzheng Xiaozheng Prescription low- and high-dosage groups, and exosome inhibitor group according to random number table method, with 6 mice in each group. The mouse model of lung pre-metastatic niche formation of gastric cancer was established by tail vein injection of MFC cells. After 12 days of administration, the lung metastasis under the intervention of Jianpi Yangzheng Xiaozheng Prescription was evaluated by observing the infiltration of tumor into lung tissue, weighing lung weight and hematoxylin-eosin (HE) staining of lung tissue. Mouse serum exosomes were extracted by ExoQuick kit and identified by transmission electron microscopy and nanoparticle tracking analysis (NTA). The content of PD-L1 in serum exosomes and the expression levels of serum transforming growth factor-β (TGF-β), interleukin-10 (IL-10) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to detect the phenotype of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) and the expression of PD-L1 in MDSC and TAM.Results:Compared with the model group, after the intervention of Jianpi Yangzheng Xiaozheng Prescription, the lung metastases of mice were reduced ( P<0.05), and the weight of metastatic tumors decreased ( P<0.05). PD-L1 in serum exosomes and the proportion of MDSC and M2 TAM in lung tissue microenvironment decreased, as well as the expression of PD-L1 on MDSC and TAM decreased ( P<0.05). The serum levels of IL-10 and IL-6 significantly decreased ( P<0.05). Conclusion:Jianpi Yangzheng Xiaozheng Prescription can reduce the proportion of MDSC and M2 TAM and the expression level of PD-L1 in the microenvironment of lung tissue before metastasis by inhibiting the transmission of gastric cancer exosome PD-L1 to MDSC and TAM, and reduce the contents of inflammatory factorsIL-10 and IL-6, so as to play a role in improving the microenvironment before lung metastasis of gastric cancer.
10.Exploration on Rules of Medication and Clinical Application of Zhongwan Point Based on Association Rules
Xin TIAN ; Yaqi YAO ; Zezhou ZHANG ; Weilu CHENG ; Shaozong CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(3):642-650
Objective To observe the rules of medication and clinical application of Zhongwan(RN12)point,thus to provide reference for the selection of acupoints in clinical treatment.Methods Collect the Zhongwan point-involved prescriptions in the literature of the last 20 years in China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP)and Wanfang Data Knowledge Service Platform,conduct strict screening,organize and record all the acupoints involved in the prescriptions,of which met the acupoint selection criteria,into Excel tables,then use IBM SPSS Statistics 25.0 software,IBM SPSS Modeler 18.0 software,Cytoscape 3.10.1 software,apriori algorithm to analyze the rules of medication and clinical application of Zhongwan point.Results After screening,a total of 781 articles with 830 acupoint-involved prescriptions were included,involves 183 acupoints and 135 diseases.With the leading five acupoints which ranked in decending order of selection was as follows:Zusanli(ST36),Neiguan(PC6),Tianshu(ST25),Guanyuan(BL26)and Qihai(RN6).The distribution of acupoints with the highest frequency of use in combination acupoints was Zusanli(61.205%support),and the meridians with a higher frequency of use in Zhongwan point-involved prescriptions were the foot-yangming stomach meridian,the foot-taiyang bladder meridian,and the conception vessel(CV),with the combination acupoints dominated by the specific acupoints of Xiahe points,He points,front-Mu points,collateral points,Shu Points,and original points,the advantageous diseases were characterized by intractable hiccups,gastritis,functional dyspepsia and so on.Among them,the diseases pertain to the digestive system were the most involved,followed by endocrine system diseases.Conclusion The data mining analysis yielded that there are certain rules to be followed in the acupoints combination of Zhongwan point,and it exerts some efficacy in the treatment of certain advantageous diseases,which can provide references for clinical treatment and scientific research.


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