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.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.
3.Research on reliability management of medical equipment supply in cardiology ward
Xi TANG ; Ting ZENG ; Yanhua DU ; Lili WU
China Medical Equipment 2024;21(3):123-128
Objective:To construct a reliability management index system of cardiology medical equipment supply,to form a reliability evaluation strategy,and to improve the effectiveness of reliability management.Methods:13 supply management items were decomposed from the three links of spare parts before use,tracking during use and post-use processing of 126 medical equipment,and the probability of work error,probability of quality problems and risk expectation of diagnosis and treatment were evaluated in the whole process management,and the whole-process management countermeasures of grading and stratification,quality standardization and department cooperation was formed.2,000 pieces(sets)of medical equipment used in The People's Hospital of Longhua from 2021 to 2022 were selected by random sampling method,and the department cooperative management[referred to as collaborative management mode,1,000 pieces(sets)times]and reliability evaluation management[referred to as evaluation management mode,1,000 pieces(sets)times]were adopted respectively.The reliability and satisfaction of medical equipment under different management modes were compared.Results:The work error probabilities of pre-use spare parts,in-use tracking,post-use processing and supply of medical equipment adopting evaluation management mode were(4.74±2.19)%,(4.39±1.85)%,(5.75±1.88)%and(8.29±1.30)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=5.367,5.663,5.432,6.847;P<0.05);the probabilities of quality problems were(4.13±1.67)%,(3.89±1.25)%,(5.28±1.84)%and(7.64±1.18)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=6.504,6.229,5.123,6.166,P<0.05);the risk expectations of diagnosis and treatment were(2.74±0.89)%,(2.47±0.96)%,(3.42±0.95)%and(4.02±1.09)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=7.027,6.509,8.915,9.266,P<0.05).The satisfaction of the relevant staff on the performance quality,sterilization specifications,supply timeliness,level of collaboration and safety of the medical equipment adopting the evaluation management mode were(93.54±4.65)%,(91.67±4.11)%,(94.58±4.34)%,(92.39±3.82)%and(90.97±3.76)%,respectively,which were higher than the collaborative management mode,the difference was statistically significant(t=2.809,3.030,2.843,4.939,3.739,P<0.05).Conclusion:The reliability management model can reduce the work errors and security risks in medical equipment supply,improve the reliability of supply and improve the quality of supply service.
4.Gegen Qinliantang and Its Modified Prescriptions Ameliorate Insulin Resistance in Type 2 Diabetes Mellitus: A Review
Yimin LIU ; Yanhua JI ; Mengjie CHEN ; Xiaojun YAN ; Hongning LIU ; Zhijun ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):256-263
Gegen Qinliantang is a representative prescription for dual releasing of exterior and interior and treating diarrhea with fever in the Treatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》). This prescription consists of Puerariae Lobatae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. The combination of the four herbal medicines has the ability to clear both the exterior and the interior, thereby halting diarrhea and clearing heat. According to the idea of treating different diseases with the same method, Gegen Qinliantang is used in clinical practice to treat type 2 diabetes mellitus (T2DM), which demonstrates positive outcomes. T2DM is a chronic metabolic disease characterized by elevated blood glucose levels. The etiology and pathogenesis of T2DM are complex, mainly related to heredity, lifestyle, environment, diet and other factors. Clinical observations and experimental studies have shown that Gegen Qinliantang and its effective ingredients have significant effects of preventing and treating T2DM. Clinically, Gegen Qinliantang is often applied with modification, or in combination with Western drugs, demonstrating better therapeutic effects than Western drugs alone. Clinical practice has confirmed that Gegen Qinliantang can effectively alleviate the clinical symptoms, reduce the occurrence of complications, and alleviate gastrointestinal adverse reactions in T2DM patients. Experimental studies have demonstrated that Gegen Qinliantang can ameliorate insulin resistance and boost pancreatic function by regulating the insulin and inflammation signaling pathways, alleviating oxidative stress, and modulating gut microbiota to treat T2DM. Nevertheless, more thorough studies remain to be carried out to decipher the mechanism of Gegen Qinliantang in ameliorating insulin resistance in T2DM. To provide theoretical and data references for the subsequent in-depth research on the mechanism of Gegen Qinliantang in treating T2DM and the prevention and treatment of this disease, this article systematically reviews the clinical and experimental research progress of Gegen Qinliantang in ameliorating insulin resistance in T2DM.
5.Genetic analysis of the false positive trisomy 7 and false negative trisomy 18 by NIPT-PLUS
Yanhua XIAO ; Ailing WANG ; Rui LI ; Jianhong WANG ; Xinfeng PANG ; Bei ZENG ; Yufei MA ; Heng WANG ; Chu ZHANG ; Pinxiao ZHANG
Chinese Journal of Medical Genetics 2024;41(1):8-13
Objective:To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis.Methods:A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq).Results:The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord.Conclusion:The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.
6.Erratum: Author correction to 'TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner' Acta Pharmaceutica Sinica B 11 (2021) 3994-4007.
Huaqing ZHENG ; Xiaolong LI ; Xin ZENG ; Chengcui HUANG ; Mingming MA ; Xiaofei LV ; Yajuan ZHANG ; Lu SUN ; Guanlei WANG ; Yanhua DU ; Yongyuan GUAN
Acta Pharmaceutica Sinica B 2023;13(9):3956-3960
[This corrects the article DOI: 10.1016/j.apsb.2021.04.013.].
7.Effect of radiofrequency combined with magnetic stimulation on mild and moderate pelvic organ prolapse
Yao TONG ; Xuhong LI ; Wenguang YAN ; Xiaoling ZENG ; Fen XIE ; Jingjing LI ; Yanhua ZHOU
Journal of Central South University(Medical Sciences) 2023;48(11):1696-1702
Objective:The efficacy of using a single electrical or magnetic stimulation for treating pelvic floor dysfunction is limited.This study aims to investigate the efficacy of radiofrequency combined with magnetic stimulation treatment for mild to moderate pelvic organ prolapse. Methods:Patients who completed the treatment in the Third Xiangya Hospital,Central South University were screened,and were divided into 2 groups based on different treatment plans.There were 28 patients who completed magnetic stimulation therapy(the magnetic stimulation therapy group)and 21 patients who completed radiofrequency combined with magnetic stimulation therapy(the combined treatment group).The pelvic organ prolapse quantitation(POP-Q),pelvic floor muscle strength,and pelvic floor ultrasound results were analyzed to assess the efficacy before and after the treatment in both groups,and the POP-Q results of 3 months after the treatment were used to evaluate the maintenance effect of the treatment mode. Results:The POP-Q evaluation results of Aa,Ap,and C points after the treatment in both groups were better than those before the treatment,with statistical significance(all P<0.05).The Aa point POP-Q result of the combined treatment group was better than that of the magnetic stimulation therapy group,with statistical significance(P<0.05).Pelvic floor ultrasound evaluation showed that the bladder neck position during the valsalva maneuver in the combined treatment group was higher than that in the magnetic stimulation treatment group,with statistical significance(P<0.05).The persistence effect of the combined treatment group was long better than that of the magnetic stimulation treatment group,with significant statistical significance(P<0.01). Conclusion:The combined treatment is more effective and has a longer lasting effect than single magnetic stimulation treatment.
8.Establishment and identification of a mitochondrial tracking system
Lin LYU ; Sihan WANG ; Quan ZENG ; Han DUAN ; Zhuang MAO ; Changyao WANG ; Xuetao PEI ; Hua WANG ; Yanhua LI
Chinese Journal of Pharmacology and Toxicology 2023;37(12):928-935
OBJECTIVE To observe whether mitochondria can be transferred from mesenchymal stem cells(MSCs)to irradiated cells by establishing a mitochondrial fluorescent reporting system.METHODS The lentiviral vector pSIN-EF1α-COX8A-DsRed2(named COX8A-DsRed2)that might guide the expres-sion of red fluorescence protein in the membrane of mitochondria was constructed.A lentivirus(named Lv-COX8A-DsRed2)was prepared in 293T cell line.Dental pulp stem cells(DPSCs)(named DPSC-COX8A-DsRed2)was infected with Lv-COX8A-DsRed2.The intracellular expression of the red fluores-cence protein in DPSC was observed under fluorescence microcopy.The mitochondrial localization of the expressed red fluorescent probe in DPSC-COX8A-DsRed2 was confirmed according to TOMM20 immunostaining and MitoTracker Green staining results,which could specifically label mitochondria.The IEC-6 cells that received 10 Gy X-ray radiation were used as an injured cell model.The co-culture system was established by supplementing DPSC-COX8A-DsRed2 into the culture plate with the irradi-ated IEC-6 labelled by CFSE for 24 h.RESULTS The imaging results of fluorescent microcopy obser-vation showed that DPSC-COX8A-DsRed2 expressed the mitochondrial fluorescent reporting system,which was co-located with TOMM20 protein and Mito Tracker Green.The imaging results of confocal fluorescence microcopy showed that the mitochondria with red fluorescent protein were transferred from DPSC-COX8A-DsRed2 to the irradiated IEC-6 cells,suggesting that the established mitochondrial fluorescent reporting system could indicate mitochondrial transfer from donor cells to injured ones.CONCLUSION DPSC-COX8A-DsRed2 stably expressing the mitochondrial fluorescent reporting system is established,which can be used to track mitochondrial transfer.
9.Erratum: Author correction to "TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner" Acta Pharm Sin B 11(12) (2021) 3994-4007.
Huaqing ZHENG ; Xiaolong LI ; Xin ZENG ; Chengcui HUANG ; Mingming MA ; Xiaofei LV ; Yajuan ZHANG ; Lu SUN ; Guanlei WANG ; Yanhua DU ; Yongyuan GUAN
Acta Pharmaceutica Sinica B 2023;13(3):1340-1343
[This corrects the article DOI: 10.1016/j.apsb.2021.04.013.].
10.Shuyuwan Regulates M1/M2 Polarization of Tumor-associated Macrophages to Inhibit Progression of Colorectal Cancer
Fengmei REN ; Chao YANG ; Jingjing ZENG ; Yanhua GUO ; Qunfang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):20-26
ObjectiveTo explore the molecular mechanism of Shuyuwan regulating polarization of tumor-associated macrophages (TAMs) to inhibit the progression of colorectal cancer (CRC). MethodThe nude mouse model of orthotopic transplantation of colon cancer was established. Male BALB/c-nu nude mice (n=28, 4 weeks old) were randomly assigned into 4 groups (n=7): Model group (normal saline) and low-, medium-, and high-dose (1.725, 2.310, 2.895 g·kg-1·d-1, respectively) Shuyuwan groups. On day 9 after the tumor block was inoculated, the mice were administrated by gavage with corresponding agents at a dose of 15 mL·kg-1 once a day, 6 days a week, and no agent on the 7th day. After two consecutive weeks of intervention, the nude mice were sacrificed and the tumor samples were collected. A part of the colon tissue and the tumor tissue was used to prepare sections, and hematoxylin-eosin (HE) staining was performed for pathological observation. The expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in the tumor tissue was detected by immunohistochemistry (IHC). The mRNA levels of interleukin-12 (IL-12), epidermal growth factor (EGF), and transforming growth factor-β1 (TGF-β1) in the tumor tissue were determined by Real-time polymerase chain reaction (PCR). Western blot was employed to determine the protein levels of iNOS, IL-12, EGF, and TGF-β1 in the tumor tissue. ResultCompared with the model group, Shuyuwan inhibited the growth of colon cancer cells in nude mice and caused the tumor cell necrosis in different degrees. The high-dose Shuyuwan group had the strongest inhibitory effect on the growth of tumor cells, which basically lost the normal morphology. Furthermore, Shuyuwan up-regulated the expression of iNOS and IL-12 in M1-type macrophages (P<0.05) and down-regulated the expression of Arg-1, EGF, and TGF-β1 in M2-type macrophages (P<0.05), which indicated the weakened polarization of macrophages toward M2 type and the enhanced polarization toward M1 type after treatment with Shuyuwan. ConclusionShuyuwan can inhibit the growth of orthotopically transplanted colon tumor by blocking the polarization of TAMs to M2 type and promoting the polarization of TAMs to M1 type.

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