1.Effect of Berberine-Baicalin Combination on Fecal Microbiota Transplantation-induced Type 2 Diabetes Mellitus Due to Internal Accumulation of Dampness-heat in Mice from Perspectives of Gut Microbiota and Metabolomics
Mengjie CHEN ; Yimin LIU ; Yun ZHOU ; Keming YU ; Min XIA ; Hongning LIU ; Yanhua JI ; Zhijun ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):52-64
ObjectiveTo investigate the mechanisms by which the combination of berberine (BBR) and baicalin (BAI) ameliorates type 2 diabetes mellitus (T2DM) due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group (n=10) and a T2DM (syndrome of internal accumulation of dampness-heat) fecal microbiota transplantation group (n=20). The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage, respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group (n=8) and a BBR-BAI group (n=11). BBR was administrated at a dose of 200 mg·kg-1, and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin (INS), triglycerides (TG), total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1, zonula occludens-1 (ZO-1), and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction(Real-time PCR) was employed to assess the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF-MS), respectively. ResultsThe BBR-BAI combination lowered the FBG, HbA1c, and INS levels (P<0.05, P<0.01) and alleviated insulin resistance (P<0.01) in T2DM mice. Additionally, BBR-BAI elevated the levels of ZO-1, occludin, and claudin-1 (P<0.05, P<0.01) and down-regulated the expression levels of TNF-α, IL-1β, and IL-6 in the colon (P<0.05, P<0.01). The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus, Phascolarctobacterium, and Akkermansia (P<0.05), while significantly decreasing the relative abundance of Alistipes, Odoribacter, and Colidextribacter (P<0.05). UPLC-Q-TOF-MS identified 28 differential metabolites, which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.
2.Investigation of Effect of Different Drying Conditions on Appearance Characteristics and Internal Indicators of Pinelliae Rhizoma Based on Standardization
Suqing LIU ; Xueli ZHANG ; Jing ZHANG ; Cong YANG ; Changfu YANG ; Jun YU ; Bingpeng ZHENG ; Huiwu LI ; Yanhua JIANG ; Chang LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):208-215
ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions, so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values(L*) of the surface, cross-section and powder of the samples, texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography(HPLC) was used to determine the contents of seven nucleoside components(uracil, hypoxanthine, uridine, inosine, guanosine, β-thymidine and adenosine) in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis(PCA) was used to comprehensively rank the data of various indicators, and partial least squares-discriminant analysis(PLS-DA) was used to screen differential components with variable importance in the projection(VIP) value>1. Furthermore, the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature, the color of the intermittently dried samples gradually deepened, while their hardness gradually decreased. Concurrently, the contents of extract, total starch, uridine and adenosine exhibited an upward trend, whereas the contents of uracil, hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group, the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose, the hardness and the total content of nucleoside components in the samples showed a downward trend, while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L* was negatively correlated with the contents of uracil, hypoxanthine and inosine, and positively correlated with the contents of uridine, guanosine and adenosine. Hardness was negatively correlated with adenosine content, and positively correlated with the contents of inosine, uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components, the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract, the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition, while uridine, uracil, guanosine, adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination, which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.
3.ARID1A IDR targets EWS-FLI1 condensates and finetunes chromatin remodeling.
Jingdong XUE ; Siang LV ; Ming YU ; Yixuan PAN ; Ningzhe LI ; Xiang XU ; Qi ZHANG ; Mengyuan PENG ; Fang LIU ; Xuxu SUN ; Yimin LAO ; Yanhua YAO ; Juan SONG ; Jun WU ; Bing LI
Protein & Cell 2025;16(1):64-71
4.Mechanism of Wendantang in Intervention of ApoE-/- Hyperlipidemic Mice Based on Liver Metabolomics
Yun ZHOU ; Songren YU ; Lu ZHANG ; Wenting LIN ; Keming YU ; Min XIA ; Zhijun ZENG ; Yanhua JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):1-9
ObjectiveTo explore the mechanism of action of Wendantang on ApoE-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group (n=6), and they were fed with regular chow, while male ApoE-/- mice constituted the high-fat group (n=30), and they were fed with a 60% high-fat diet. After 11 weeks of model establishment, the mice in the high-fat group were randomly divided into the model group, simvastatin group (3.3 mg·kg-1), and high-dose, medium-dose, and low-dose groups of Wendantang (26, 13, 6.5 g·kg-1, respectively, in terms of crude drug amount), with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline, and all groups continued to be fed their respective diets, receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (NEFA), blood glucose (GLU), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin (HE) staining, and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group, the model group exhibited significantly increased body weight, blood lipid levels, and liver function (P<0.05, P<0.01), with disordered liver tissue structure, swollen hepatocytes, and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group, the simvastatin group and Wendantang groups showed significantly reduced body weight, TG, NEFA, GLU, ALT, and AST levels (P<0.05, P<0.01), with a significant increase in HDL-C levels (P<0.05, P<0.01), demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration, tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group, with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified, mainly including chenodeoxycholic acid, hyocholic acid, taurine, glycocholic acid, dihydroceramide, hydroxy sphingomyelin C14∶1, arachidonic acid, and linoleic acid, enriching 22 metabolic pathways, with 4 being the most significant (P<0.05), namely primary bile acid biosynthesis, sphingolipid metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE-/- hyperlipidemic mice, which may be related to the regulation of primary bile acid biosynthesis, sphingolipid metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism pathways.
5.Epidemiology and management patterns of chronic thromboembolic pulmonary hypertension in China.
Wanmu XIE ; Yongpei YU ; Qiang HUANG ; Xiaoyan YAN ; Yuanhua YANG ; Changming XIONG ; Zhihong LIU ; Jun WAN ; Sugang GONG ; Lan WANG ; Cheng HONG ; Chenghong LI ; Jean-François RICHARD ; Yanhua WU ; Jun ZOU ; Chen YAO ; Zhenguo ZHAI
Chinese Medical Journal 2025;138(8):1000-1002
6.Analysis on distribution and trend of malignant tumor incidence and mortality in Dehui City and Yanji City in Jilin Province from 2009 to 2016
Xinyi YU ; Zhifang JIA ; Yuzheng ZHANG ; Yuchen PAN ; Yangyu ZHANG ; Yanhua WU ; Donghui CAO ; Jing JIANG
Journal of Jilin University(Medicine Edition) 2025;51(3):797-806
Objective:To clarify the changes in incidence and mortality of various cancers based on analysis on registration data of malignant tumor incidence and mortality from Dehui City and Yanji City in Jilin Province.Methods:The incidence and mortality data of malignant tumors from 2009 to 2016 in Dehui City and Yanji City in Jilin Province,were collected from the Chinese Cancer Registry Annual Report published by the National Cancer Center.The number of cases,deaths,crude incidence rate,crude mortality rate,age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and annual percentage change(APC)of the malignant tumors were analyzed by cancer sites and genders.Results:From 2009 to 2016,the CIR of malignant tumors in Dehui City(APC=1.2%,P=0.019)and Yanji City(APC=3.6%,P=0.058)showed an increasing trend.After standard population age adjustment,the ASIR in males in Dehui City showed a significant decline(APC=-5.7%,P=0.021),while the ASIR in females exhibited an overall downward trend,but the difference was not significant(APC=-2.2%,P=0.111).In Yanji City,the ASIR in males(APC=-1.4%,P=0.535)and females(APC=0.0%,P=0.988)showed no significant changes.The CMR of malignant tumors in Dehui City(APC=1.9%,P=0.001)and Yanji City(APC=5.9%,P=0.001)showed a continuous upward trend.After age-standardization,the ASMR in males(APC=-3.1%,P=0.100)and females(APC=-4.2%,P=0.053)in Dehui City,as well as in males(APC=-1.3%,P=0.438)in Yanji City,showed a slight downward trend.Although the ASMR in females in Yanji City showed a slight increase,the difference was not statistically significant(APC=0.5%,P=0.838).In 2016,the most common malignant tumor in terms of both incidence and mortality in Dehui City was lung cancer,with a CIR of 60.76/100 000 and a CMR of 46.96/100 000.In Yanji City,the most common malignant tumor was liver cancer,with a CIR of 49.04/100 000 and a CMR of 51.09/100 000.Conclusion:Lung cancer,liver cancer,and gastric cancer are the major malignant tumors threatening residents in Dehui City,Yanji City,and even the entire Jilin Province,and should be prioritized in cancer prevention and control efforts.Early diagnosis and treatment should be strengthened.
7.Effect of timing of minimally invasive puncture and drainage on the outcome of patients with hypertensive intracerebral hemorrhage in basal ganglia region
Yanhua WANG ; Teng XIE ; Xiaoping YU ; Zhijun HUANG ; Wen LIU
International Journal of Cerebrovascular Diseases 2025;33(2):108-112
Objective:To investigate the correlation between the timing of minimally invasive puncture drainage and the outcome of patients with hypertensive intracerebral hemorrhage (HICH) in the basal ganglia region.Methods:Patients with HICH in the basal ganglia region underwent minimally invasive puncture and drainage at Hanchuan People's Hospital from January 2019 to September 2023 were selected. According to the timing of surgery, the patients were divided into onset to surgery time ≤12-hour group and >12-hour group. According to the modified Rankin Scale score at 90 days after onset, they were divided into a good outcome group (0-2) and a poor outcome group (>2). Multivariate logistic regression analysis was used to evaluate the independent influencing factors of functional outcome. Results:A total of 150 patients were included, with 78 males (52.00%), aged 53.15±4.35 years (range, 40-75 years). Eighty-six patients (57.33%) underwent surgery within 12 hours after onset, while 64 (42.67%) underwent surgery after 12 hours; 97 patients (64.67%) had good outcome, while 53 (35.33%) had poor outcome. Univariate analysis showed that compared with the onset to surgery time ≤12-hour group, the onset to surgery time >12-hour group had a longer time from onset to admission, a larger postoperative hematoma volume, longer hospitalization time, lower postoperative hematoma clearance rate, and a higher proportion of patients with poor outcome and deaths within 90 days (all P<0.05). Compared with the good outcome group, the poor outcome group had a longer time from onset to admission, higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, larger baseline and postoperative hematoma volumes, and a higher proportion of patients with onset to surgery time >12 hours. However, the postoperative hematoma clearance rate, baseline Glasgow Coma Scale (GCS) score, and the proportion of patients with baseline GCS score >8 was lower in the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that the higher baseline NIHSS score (odds ratio [ OR] 1.847, 95% confidence interval [ CI] 1.362-2.503; P=0.001) and the time from onset to surgery >12 hours (compared with ≤12 hours: OR 1.347, 95% CI 1.058-1.715; P=0.016) were the independent risk factors for poor outcome, while higher baseline GCS scores ( OR 0.723, 95% CI 0.558-0.937; P=0.006) and higher postoperative hematoma clearance rates ( OR 0.615, 95% CI 0.462-0.819; P=0.004) were the independent protective factors for good outcome. Conclusion:In patients with HICH in basal ganglia, it is ideal to perform minimally invasive puncture and drainage within 12 h after onset, and the postoperative recovery is relatively better.
8.Evaluation of radiation-induced intestinal injury via a new human intestinal organ-on-a-chip model
Liang HU ; Lin LÜ ; Xuan TANG ; Sihan WANG ; Zuyin YU ; Yanhua LI
Military Medical Sciences 2025;49(3):171-177
Objective To establish a human intestinal organ-on-a-chip model using a multi-array chip array to simulate the microphysiological structure of the human intestine and to investigate the impact of ionizing radiation on radiation-induced damage to human intestinal cells.Methods Caco-2 and human umbilical vein endothelial cells(HUVECs)were co-cultured in an organ chip.The cells were subjected to fluid shear stress via a precision shaker.After 7 days of dynamic culture,the morphological structure of intestinal epithelial cells and venous endothelial cells within the intestinal organ chip was examined using phase contrast microscopy,immunofluorescence staining,and confocal microscopy for three-dimensional(3D)imaging.γ-H2AX and TUNEL immunofluorescence staining were employed to assess DNA damage and apoptosis in intestinal epithelial cells two days post-irradiation.Villin immunofluorescence staining was used to evaluate villus height three days post-irradiation.EdU incorporation assay and Ki67 immunofluorescence staining were conducted to observe the effects of ionizing radiation on the proliferation of intestinal epithelial cells.Results After 7 days of dynamic culture,phase contrast microscopy and immunofluorescence staining combined with confocal 3D imaging revealed that the upper intestinal epithelial cells in the middle compartment of the chip formed a 3D intestinal villus structure,while the vascular endothelial cells in the lower compartment developed a vascular network structure.The chip was subsequently irradiated by 10 Gy X-ray.Immunofluorescence staining results indicated that the mean fluorescence intensity of γ-H2AX and TUNEL in the irradiated group was significantly higher than in the non-irradiated group 2 days after irradiation(P<0.01),and that the proportion of EDU+and Ki67+cells in the irradiated group was significantly lower than in the non-irradiated group three days after irradiation(P<0.05).Conclusion Caco-2 cells and HUVECs co-culture on an organ chip can generate the biomimetic structure of human intestinal villus.Ionizing radiation has been found to shorten intestinal villus,increase DNA damage and apoptosis in intestinal epithelial cells,and inhibit the proliferation of these cells.
9.Effect of Yiqi Tongmai Formula in Intervening in Liver Inflammation and Lipidosis in ApoE-∕- Mice Based on NF-κB/NLRP3 Signaling Pathway
Yuhan CHEN ; Quanna REN ; Kun WANG ; Tingting SU ; Yanhua YANG ; Ming MA ; Yu ZHANG ; Xu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):64-72
ObjectiveTo investigate the effect of Yiqi Tongxin formula (YQTM) on liver inflammation in apolipoprotein E-∕- (ApoE-∕-) mice by regulating the nuclear transcription factor-κB (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway. MethodForty ApoE-∕- mice were randomly divided into a model group, an atorvastatin group (positive drug group), and low-, medium-, and high-dose YQTM groups (0.39, 0.78, 1.56 g·kg-1). Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks, oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin (HE) staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in mouse serum, as well as total cholesterol (TC) and triglyceride (TG) in the liver. Interleukin-1β (IL-1β) and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB, NF-κB inhibitory protein (IκB), IκB kinase β (IKKβ), phosphorylated NF-κB (p-NF-κB), phosphorylated IκB (p-IκB), phosphorylated IKK β (p-IKKβ), NLRP3, and Caspase-1 in the livers of mice. ResultCompared with the blank group, the model group showed severe aortic lipidosis, and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles(P<0.01). The serum levels of TG, TC, LDL-C, AST, and ALT were significantly elevated in the mice(P<0.01). TG and TC levels were elevated in the liver(P<0.01). The levels of IL-1β and IL-18 in liver tissue, as well as the protein expression levels of NF-κB, IκB, IKKβ, p-NF-κB, p-IκB, p-IKKβ, NLRP3, and Caspase-1 in the liver were significantly elevated(P<0.01). Compared with the model group, the aortic arch plaques of mice in each YQTM group were attenuated, and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated(P<0.05,P<0.01). The serum levels of TG, TC, LDL-C, AST, and ALT were significantly reduced(P<0.05,P<0.01). TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue, as well as protein expression levels of NF-κB, IκB, IKKβ, p-NF-κB, p-IκB, p-IKKβ, NLRP3, and Caspase-1 in the liver were significantly reduced(P<0.05,P<0.01). ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.
10.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.

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