1.Gelian Tiaotang Pills Ameliorate Renal Fibrosis in db/db Mice via NLRP3/Caspase-1/GSDMD Pathway
Lihui FAN ; Zhigang WANG ; Xia YANG ; Xiaolong MEI ; Kun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):136-145
ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3)/cysteinyl aspartate-specific proteinase (Caspase)-1/gasdermin D (GSDMD) signaling pathway. MethodsForty db/db mice were randomly assigned into model, positive control (0.001 3 g·kg·d-1 dapagliflozin suspension), and high-, medium-, and low-dose Gelian Tiaotang pills (3.12, 1.56, and 0.78 g·kg·d-1 suspension of Gelian Tiaotang pills, respectively) groups, with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water, while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose (FBG) and body mass were measured every 4 weeks. Kidneys were weighed after sampling, and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). The pathological changes, extracellular matrix deposition, and renal fibrosis degree were examined by hematoxylin-eosin, periodic acid-schiff (PAS), and Masson staining, respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin (IL)-1β and IL-18 in the renal tissue. Immunohistochemistry (IHC) was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, and GSDMD-N in the renal tissue. ResultsCompared with the normal group, the model group generally had poor general states and increases in the body mass, kidney weight, kidney index, and levels of FBG, TG, TC, SCr, and BUN (P<0.01). In addition, glomerular pyknosis, increased matrix, vacuolar degeneration of renal tubular epithelial cells, and interstitial infiltration of inflammatory cells were observed in the model group (P<0.01), together with rises in the levels of IL-1β and IL-18 in the renal tissue (P<0.01) and up-regulated protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-N, fibronectin, and collagen Ⅰ in the renal tissue (P<0.01). Compared with the model group, 12 weeks of drug interventions reduced the body mass, kidney weight, and kidney index and lowered the levels of FBG, TG, TC, SCr, and BUN in the serum and IL-1β and IL-18 in the renal tissue (P<0.05, P<0.01). Furthermore, drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-N, fibronectin, and collagen Ⅰ in the renal tissue (P<0.05, P<0.01). The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway, thus delaying the process of renal fibrosis in diabetes.
2.Bacterial contamination of platelets apheresis: a single-center retrospective analysis
Yuanyuan LUO ; Chunya MA ; Lihui FU ; Zeshan WANG ; Yang YU
Chinese Journal of Blood Transfusion 2025;38(2):233-237
[Objective] To evaluate the risk of bacterial contamination of platelets apheresis and improve the clinical diagnosis rate of transfusion-transmitted bacterial infections. [Methods] A retrospective analysis was conducted on 11 cases involving bacterial contamination detected in apheresis platelets during quality inspections at our center from 2021 to 2023, as well as cases of transfusion-transmitted bacterial infection (TTBI) caused by platelet transfusion. The return of positive platelet bacteria test results and clinical transfusion adverse reactions were statistically analyzed. [Results] There were 9 donors with bacteria-contaminated platelets, of which 3 were reported as clinical transfusion reaction, 4 were detected by quality sampling, and 2 were identified by appearance detection before transfusion. The bacterial contamination rate of platelets was about 0.08% (9/10 762). The contaminated platelets were involved in 11 cases of TTBI, with an incidence of TTBI of approximately 0.05% (11/21 916). Only 3 cases of transfusion reactions were clinically reported, while the rest were case tracking with positive results of platelet bacterial test from quality sampling. The clinical return rate of TTBI was 27.27% (3/11), with an average reporting time of 8.12 hours after the occurrence of transfusion reactions. The majority of the contaminated platelets were detected at the end stage of storage, with 55.56% (5/9) of platelets collected on the 4th day after collection. Partial contaminated platelets were identified through quality sampling, with a positive rate of 2.78% (4/144). [Conclusion] The platelet bacterial contamination rate is high, but with low clinical return rate. It is recommended to conduct routine platelet bacterial monitoring and improve clinical diagnostic level.
3.Mechanism and Combination Therapy of Berberine in Treatment of Nonalcoholic Fatty liver Disease:A Review
Xiaojie WANG ; Heng ZHANG ; Sutong LIU ; Lihui ZHANG ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):269-281
Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the world. Because of its complex pathogenesis, high clinical prevalence and large population, it poses a great threat and challenge to public health in the world. Therefore, active intervention measures are needed. Currently, western medicine is effective in reducing weight, reducing liver fat content, improving glucose-lipid metabolism and insulin resistance. However, for patients with NAFLD-related fibrosis and cirrhosis, there is still a lack of sufficient histological evidence to support its benefits, and randomized controlled trials are still needed to clarify. Lifestyle intervention is an important cornerstone for the treatment of NAFLD, but there are many problems such as poor implementation and low compliance of patients, and the clinical efficacy is not ideal. Traditional Chinese medicine(TCM) has the significant advantages of multiple pathways and multiple targets. Berberine, the active ingredient of TCM, can interfere with the production of NAFLD from multiple pathways, including increasing energy consumption, weight loss, improving glucose-lipid metabolism, improving insulin resistance, anti-inflammatory, anti-oxidation, regulating intestinal flora, restoring bile acid homeostasis, anti-fibrosis and so on, which can play a positive role in the treatment of NAFLD. At the same time, it was found that the combination of BBR with Chinese and western medicines had significant advantages in promoting drug absorption, improving oral bioavailability, increasing the highest biological distribution in the liver, enhancing the overall therapeutic effect of NAFLD, and reducing adverse drug reactions, which could provide reference for clinical medication.
4.Clinical Study on Treatment of Non-alcoholic Steatohepatitis Patients with Dyslipidemia by Dizhuo Huayu Prescription with Catgut Embedding Therapy
Xiaoyan LIU ; Dongfang SHANG ; Lihui ZHANG ; Chenlu ZHAO ; Siying WANG ; Huaxin CHEN ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):152-159
ObjectiveTo observe the clinical efficacy and safety of Dizhuo Huayu prescription combined with catgut embedding therapy in patients with nonalcoholic steatohepatitis (NASH) and dyslipidemia and explore the effect of the combined therapy on inflammatory cytokines interleukin (IL)-18 and IL-1β. MethodsA total of 82 patients with NASH and dyslipidemia from the Gastroenterology Department of the First Affiliated Hospital of Henan University of Chinese Medicine were randomly divided into a control group and a treatment group, with 41 patients in each group. The control group received Polyene Polyenylphosphatidylcholine Capsules, while the treatment group received Dizhuo Huayu prescription granules combined with catgut embedding. The treatment duration was 24 weeks for both groups. At weeks 0, 12, and 24, the traditional Chinese medicine (TCM) syndrome score, body mass index (BMI), liver fat content assessed by Fibroscan (CAP value), the level of alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA), and the expression of inflammatory cytokines IL-18 and IL-1β in serum were observed. Adverse reactions in both groups were recorded. ResultsA comparison of the comprehensive therapeutic effects between the two groups after 24 weeks of treatment revealed that the total effective rate was 62.16% (23/37) in the control group and 85.71% (30/35) in the treatment group, with a statistically significant difference (χ2 = 5.14, P<0.05). At weeks 12 and 24 after treatment, the TCM syndrome score, BMI, CAP value, TC, TG, LDL-C, and FFA were all significantly lower in both groups compared to pre-treatment levels, while the HDL-C level significantly increased (P<0.05). The effect was better at week 24 (P<0.05) than at week 12 (P<0.05), and the treatment group showed better outcomes than the control group at weeks 12 and 24 after treatment (P<0.05). After 24 weeks of treatment, both groups exhibited significant reductions in IL-18 and IL-1β levels (P<0.05). The treatment group demonstrated superior efficacy compared to the control group after treatment (P<0.05). Both groups experienced decreases in ALT, AST, and GGT levels after treatment (P<0.05). However, there were no statistically significant differences between the 12-week and 24-week post-treatment values within each group, nor were there significant differences between the two groups. No significant adverse reactions were observed in both groups. ConclusionThe Dizhuo Huayu prescription combined with catgut embedding therapy is safe and effective in treating patients with NASH and dyslipidemia, exhibiting hepatoprotective, anti-inflammatory, lipid-regulating, and weight-reducing effects.
5.Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy
Rui WANG ; Tiantian BAN ; Lihui XUE ; Xinyi FENG ; Jiyuan GUO ; Jiaqi LI ; Shenghe JIANG ; Xiaolei HAN ; Baofeng HU ; Wenli ZHANG ; Naijun WU ; Shuang LI ; Yajuan QI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):66-77
ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang (BWT) on non-alcoholic fatty liver disease (NAFLD) and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups: normal control, model, positive drug (pioglitazone hydrochloride 1.95×10-3 g·kg-1), and low-, medium-, and high-dose BWT (1.3,2.5 and 5.1 g·kg-1). Following a 12-week high-fat diet (HFD) inducement, the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week, glucose tolerance (GTT) and insulin tolerance (ITT) tests were conducted. Subsequently, the mice were euthanized for the collection of liver tissue and serum, and the subcutaneous adipose tissue (iWAT) and epididymal adipose tissue (eWAT) were weighed. Serum levels of total triglycerides (TG) and liver function indicators,such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined. Histological examinations, including oil red O staining, hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy, were performed to evaluate hepatic lipid deposition, pathological morphology, and ultrastructural changes, respectively. Meanwhile, Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to analyze alterations, at both gene and protein levels, the insulin signaling pathway molecules, including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 (IRS1/2/Akt/FoxO1), glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase (Pepck) and glucose-6-phosphatase (G6Pase), lipid metabolism-related genes stearoyl-coA desaturase-1 (SCD-1) and carnitine palmitoyltransferase-1 (CPT-1), fibrosis-associated molecules α-smooth muscle actin (α-SMA), type Ⅰ collagen (CollagenⅠ), and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3(TGF-β1/p-Smad/Smad2/3), inflammatory factors such as interleukin(IL)-6, IL-8, IL-11, and IL-1β, autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1, and the expression of mammalian target of rapamycin (mTOR). ResultCompared with the model group, BWT reduced the body weight and liver weight of NAFLD mice(P<0.05, P<0.01), inhibited liver lipid accumulation, and reduced the weight of white fat: it reduced the weight of eWAT and iWAT(P<0.05, P<0.01) as well as the serum TG content(P<0.05, P<0.01). BWT improved the liver function as reflected by the reduced ALT and AST content(P<0.05, P<0.01). It improved liver insulin resistance by upregulating IRS2, p-Akt/Akt, p-FoxO1/FoxO1 expressions(P<0.05). Besides, it improved glucose and lipid metabolism disorders: it reduced fasting blood glucose and postprandial blood glucose(P<0.05, P<0.01), improved GTT and ITT(P<0.05, P<0.01), reduced the expression of Pepck, G6Pase, and SCD-1(P<0.01), and increased the expression of CPT-1(P<0.01). The expressions of α-SMA, Collagen1, and TGF-β1 proteins were down-regulated(P<0.05, P<0.01), while the expression of p-Smad/Smad2/3 was downregulated(P<0.05), suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6, IL-8, IL-11 and IL-1β(P<0.01) and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression(P<0.05)while downregulating the expression of p62/SQSTM1 and mTOR(P<0.05). ConclusionBWT ameliorates NAFLD by multifaceted improvements, including improving IR and glucose and lipid metabolism, anti-inflammation, anti-fibrosis, and enhancing autophagy. In particular, BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.
6.Evaluation of perioperative nutritional status and body composition in patients with stomach neoplasms
Hong WANG ; Zhijie DING ; Yafang YE ; Lihui LIN ; Dandan KANG ; Yanping YUAN ; Lei LI
Chinese Journal of Practical Nursing 2024;40(10):772-779
Objective:To investigate the nutritional risk, incidence of malnutrition, and intake of three major energy-supplying nutrients, analyze changes in their body composition and the possible influencing factors in patients with stomach neoplasms during perioperative period in order to provide a theoretical basis for the nutritional management of patients with stomach neoplasms during perioperative period.Methods:This was a cross-sectional study. A total of 105 patients who underwent gastric cancer radical surgery in the Gastrointestinal Department of Zhongshan Hospital Affiliated to Xiamen University from June 2021 to May 2023 were taken as the research subjects using fixed-point continuous sampling method. They were recruited for screening and assessment using Nutritional Risk Screening 2002 (NRS 2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Nutrients intake during the perioperative period were investigated using the 24-h recall method and dietary diary method, etc. Body compositions were measured using the bioelectrical resistance method.Results:Among the 105 patients, there were 78 males and 27 females, with an average age of (61.5 ± 10.3) years. About 83.8% (88/105) gastric cancer patients were at nutritional risk and 82.9% (87/105) were malnourished. The preoperative and postoperative energy intake were (1 646.1 ± 321.5) and (1 317.2 ± 365.8) kcal (1 kcal=4.184 kJ), respectively, which were significantly lower than the target amount of (1 896.7 ± 262.9) kcal, the difference was statistically significant ( t=6.23, 8.29, both P<0.05).The preoperative body mass, muscle mass, skeletal muscle, fat mass, and skeletal muscle index were (51.5 ± 9.6), (40.8 ± 6.0), (23.6 ± 4.0), (8.3 ± 4.9) kg, and 6.7 ± 0.8 respectively, while the postoperative values were (50.0 ± 9.1), (39.8 ± 6.0), (22.8 ± 3.6), (7.8 ± 5.2) kg, and 6.5 ± 0.8 respectively, with statistically significant differences between the two groups ( t values were 2.89-10.61, all P<0.05). Logistic multivariate regression analysis showed that the operation time ( OR=3.984, 95% CI 1.433-11.080, P<0.05) and energy satisfaction ( OR=0.053, 95% CI 0.005-0.610, P<0.05) were independent influencing factors for the degree of skeletal muscle loss. Conclusions:During perioperative period, the gastric cancer patients had poor nutritional status with insufficient nutrient intake and accelerated loss of body muscle and fat. Therefore, it was necessary to conduct a comprehensive nutritional evaluation for patients with stomach neoplasms during perioperative period in time and take steps to promote recovery by providing individualized nutritional therapy.
7.Research progress in ulna impingement syndrome
Kai WANG ; Yi ZHENG ; Lihui ZHOU
Journal of Shenyang Medical College 2024;26(2):200-203
Ulna impingement syndrome is the main cause of wrist ulnar pain.It is caused by repeated impingement between the ulnar bone,triangular fibrocartilage complex,lunate bone and triangular bone,resulting in long-term overload of the ulnar side of wrist,affecting local blood supply and joint lubrication fluid nutrition disorders,and finally causing a series of pathological changes and clinical symptoms of joint degenerative diseases.The main clinical manifestations are pain on the ulnar side of the wrist,which gradually aggravated with repeated strong grasping activities,forearm pronation or ulnar deviation of the wrist.At present,the diagnosis of ulna impingement syndrome mainly depends on the symptoms,physical examination,imaging examination and wrist arthroscopy.Conservative treatment can be selected for ulnar impaction syndrome,but the effect is often poor.Therefore,surgery is still the main treatment.The surgical methods mainly include ulna shortening osteotomy,Wafer,Darrach and Sauvé-Kapandji,and the former two are the most commonly used.This article reviews the progress of diagnosis and treatment of ulna impingement syndrome.
8.Correlation between IL-17 gene polymorphism and type 2 diabetes mellitus in Han population in southeast Shanxi Province
Yan LI ; Qi WANG ; Lu ZHENG ; Lihui FENG ; Li MA ; Jian WEI ; Liangshu LIU
The Journal of Practical Medicine 2024;40(5):695-701
Objective To determine the correlation between single-nucleotide polymorphisms of IL-17 with type 2 diabetes in Han population in southeastern Shanxi Provincein.Methods The basic information and related clinical data of the subjects were collected of normal healthy controls and T2DM.Whole blood DNA was extracted,and IL-17 polymorphisms(rs2275913,rs3819024,rs4711998 and rs8193036)were analyzed by using a polymerase chain reaction-high temperature ligase reaction.Results There was no significant difference in the genotype and allele frequency distribution of the four SNP loci of IL-17 gene between the two groups(P>0.05).IL-17 polymorphism was not linked with T2DM in multiple genetic models after controlling for age,BMI,WC,and dyslipidemia(P>0.05).Further analysis showed that the levels of AA genotype was substantially lower of FPG and HOMA-IR levels when compared with the AG and GG genotypes,and the differences among the three groups were statistically significant(P<0.05).However,BMI,FINS,HbA1c and HOMA-βwas no statistical significance among the three groups(P>0.05).Besides,WC and HOMA-IR of AA genotype(rs3819024)were notable higher than those of GG genotype in T2DM group(P<0.05).Conclusions The IL-17 gene polymorphisms rs2275913,rs3819024,rs4711998,and rs8193036 in the Han population of southeast Shanxi Province may not be associated with T2DM.In this region Han T2DM patients,AA genotype at rs2275913 of the IL-17 gene is associ-ated to FPG and HOMA-IR,while GG genotype at rs3819024 is related to WC and HOMA-IR,which could be the potential genotype of IL-17 impacting glucose metabolism.
9.Expression and in vitro activity of a neutralizing antibody against West Nile virus that reduces antibody-dependent enhancement
Xiangjun HAO ; Nan CHEN ; Wanlu ZHU ; Jing WANG ; Guojiang CHEN ; Chunxia QIAO ; Xinying LI ; Beifen SHEN ; Jiannan FENG ; Lihui CHAI ; He XIAO
Chinese Journal of Microbiology and Immunology 2024;44(1):44-49
Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.
10.Mechanism of Yantiao Fang regulating the Rho/ROCK signaling pathway in apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis
Qian CHEN ; Di WANG ; Dingyi ZHANG ; Sailei JIA ; Lihui WANG ; Yujing CAO ; Xian LI ; Yanhong LI
Chinese Journal of Comparative Medicine 2024;34(2):16-24
Objective To investigate the effect of Yantiao Fang on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating the Rho/ROCK signaling pathway.Methods Seventy BALB/c mice were randomly divided into normal,sham,and model groups.Except for normal and sham groups,mice were subjected to cecal ligation and perforation to establish a mouse model of acute gastrointestinal injury caused by sepsis.The mouse models were randomly divided into model,Low,Medium,and High dose of Yantiao Fang,and ROCK inhibitor groups.Histopathological changes of the ileum were observed by HE staining.Serum levels of IL-1β,IL-6,TNF-α,and IL-10 were measured by ELISA.PCNA and Ki-67 expression was detected by immunohistochemistry.Cleaved caspase3 and Bax expression was detected by Western blot.ROCK and MLC mRNA expression in the ileum was measured by RT-qPCR.Results Compared with normal and sham groups,Chiu's pathological score,proinflammatory factor(IL-1β,IL-6,and TNF-α)levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were increased in the model group(P<0.05).Moreover,anti-inflammatory mediator IL-10 and expression of PCNA and Ki-67 in the ileum were decreased in the model group(P<0.05).Compared with the model group,histopathological changes of the ileum in all Yantiao Fang groups were improved by various degrees with the increase in dose.Chiu's pathological score,IL-1β,IL-6,and TNF-α serum levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were decreased in Yantian Fang groups(P<0.05).The IL-10 level and expression of PCNA and Ki-67 in the ileum were increased in Yantian Fang groups(P<0.05).Conclusions Yantiao Fang may inhibit apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury due to sepsis by regulating the Rho/ROCK signaling pathway,thereby alleviating intestinal tissue inflammation and ultimately preventing intestinal mucosal tissue injury.

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