1.Mechanism of Qishen Yiqi Dropping Pills in regulating gut microbiota and ROS/TXNIP/NLRP3 signaling pathway to improve chronic heart failure in rats
Lifei LYU ; Tingting ZHU ; Fan DING ; Yingdong LU ; Xiangning CUI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):354-369
Objective:
This study explored the regulatory effects of QiShen Yiqi Dropping Pills (QSYQ) on chronic heart failure (CHF) in rats and their related mechanisms based on the gut microbiota and reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.
Methods:
Sixty-five SPF-grade male SD rats were used to establish a CHF model through subcutaneous multiple injections of isoproterenol (ISO) combined with exhaustion and food control methods. The modeled rats were randomly divided into model, captopril (5.30 mg/kg), and QSYQ low-, medium-, and high-dose groups (0.08, 0.16, and 0.32 g/kg, respectively), with 11 rats per group, plus a blank group of seven rats. The medication groups were given corresponding drugs by gavage, whereas the blank and model groups were administered an equivalent volume of purified water continuously for four weeks. Rat heart function was assessed via transthoracic echocardiography, and myocardial tissue pathology changes were observed through hematoxylin and eosin staining. Serum levels of brain natriuretic peptide (BNP), lipopolysaccharide (LPS), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were measured using an enzyme-linked immunosorbent assay. Automated biochemical analyzers were used to determine creatine kinase (CK), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) content. Myocardial ROS levels were examined using flow cytometry; myocardial TXNIP and NLRP3 expression were detected using immunohistochemistry. Real-time qPCR and Western blotting were used to examine myocardial mRNA and protein expression of TXNIP, NLRP3, apoptosis-related spot-like protein (ASC), caspase-1, and IL-1β, as well as myocardial thioredoxin (Trx) and colonic tight junction proteins (zonula occludens-1, ZO-1), occludin, and claudin-5. Differences in the gut microbiota of the blank, model, and QSYQ high-dose groups were determined using high-throughput 16S rDNA sequencing.
Results:
Compared to the blank group, the model group exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01); increased serum BNP, LPS, IL-18, and IL-1β (P<0.01) levels; increased CK, LDH, and CK-MB (P<0.01) contents; visible myocardial tissue fibrous edema, wavy appearance, cytoplasmic loosening, round vacuolar degeneration, local tissue fibrous dissolution replaced by proliferative connective tissue, accompanied by inflammatory cell infiltration; significantly increased myocardial ROS levels (P<0.01); and significantly increased myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly increased (P<0.05, P<0.01, respectively), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly decreased (P<0.01). Compared to the model group, the QSYQ high-dose group showed the most significant changes (P<0.05, P<0.01), with significant increases in LVEF and LVFS (P<0.01); significant decreases in serum BNP, LPS, IL-18, and IL-1β levels (P<0.01); significant reductions in CK, LDH, and CK-MB content (P<0.01); improved myocardial tissue damage; significantly decreased myocardial ROS levels (P<0.01); and significantly reduced myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly decreased (P<0.05, P<0.01), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly increased (P<0.01). 16S rDNA sequencing results confirmed that the gut microbiota of rats changed after modeling and drug intervention, with significant differences in both α- and β-diversity. Compared to the blank group, at the family level, the abundance of Oscillospiraceae decreased (P<0.05), whereas the abundance of Lactobacillaceae increased. At the species level, the abundance of Segatella copri and Treponema succinifaciens increased, whereas the abundance of Kineothrix alysoides (P<0.05), Ruminococcus callidus, and Prevotellamassilia timonensis decreased. Compared to the model group, at the family level, the abundance of Oscillospiraceae increased (P<0.05) in the QSYQ high-dose group, whereas the abundance of Lactobacillaceae decreased. At the species level, the abundance of Segatella copri and Treponema succinifaciens decreased, whereas the abundance of Kineothrix alysoides increased (P<0.05).
Conclusion
QSYQ can regulate the relative abundance of symbiotic bacteria Kineothrix alysoides in the intestines, reduce serum LPS levels, inhibit the ROS/TXNIP/NLRP3 signaling pathway, and improve inflammatory responses, thereby exerting therapeutic effects on CHF.
2.Methacrylated dermal extracellular matrix hydrogel promotes repair of abdominal wall defects
Zhongyu LIU ; Wenya LI ; Yonghong FAN ; Shuang LYU ; Juan PEI ; Yaqin CHEN ; Beiyu LIU ; Hongyu SUN
Chinese Journal of Tissue Engineering Research 2025;29(10):2074-2082
BACKGROUND:Synthetic polymers,such as polypropylene and polyester,used for the treatment of abdominal wall defects not only lack biodegradability and bioactivity but also fail to meet the demands of complex and irregular wounds.Therefore,finding bioactive materials with low immunogenicity and good histocompatibility has become a hot spot in the repair of abdominal wall defects. OBJECTIVE:To prepare methacryloyl modified dermal extracellular matrix hydrogel and explore its potential application in abdominal wall defect. METHODS:(1)The porcine dermis was acellular with 0.25%trypsin and 1%Triton X-100 in turn to obtain the dermal extracellular matrix.After pepsin digestion and methacrylic anhydride modification,the methacrylated dermal extracellular matrix hydrogel was formed by photocrosslinking.The microscopic morphology of the hydrogel was observed by scanning electron microscope,and its rheological properties,swelling properties and other physical and chemical properties were tested.(2)Mice fibroblasts(L929)were inoculated into methacrylated dermal extracellular matrix hydrogel to detect the cell compatibility.(3)Totally 12 SD rats were randomly divided into two groups(n=6)to create abdominal wall defect model with peritoneum preserved.The defect site of the polypropylene group was filled with polypropylene material,and the hydrogel group was filled with methacrylated dermal extracellular matrix hydrogel.The wound skin of both groups was covered with polypropylene material.The wound healing was observed and histological analysis was carried out. RESULTS AND CONCLUSION:(1)Enzymatic hydrolysis had a good decellularization effect on porcine dermis after decellularization,and the original glycosaminoglycans and collagen were well retained.Scanning electron microscope observation revealed that the dermal extracellular matrix hydrogel presented loose and porous structure.The aperture was between 70 and 120 μm.The swelling ratio was(16.88±3.24)%and the water absorption was(94.24±1.11)%.The rheological property test showed that the methacrylated dermal extracellular matrix hydrogel was stable and had shear thinning characteristics,with injectability.(2)CCK-8 assay and live/dead staining showed that methacrylated dermal extracellular matrix hydrogel had good cell compatibility.(3)The results of animal experiments showed that the skin wound healing rate of the experimental group was higher than that of the control group at 7,10,and 14 days after operation(P<0.05).Hematoxylin-eosin and Masson staining of skin and muscle tissue exhibited that compared with the polypropylene group,the skin wound epithelialization,hair follicle formation,collagen fiber arrangement,and neovascularization were better in the hydrogel group 14 days after surgery.The skin wound new tissue structure was similar to the normal tissue at 28 days after surgery,and scar hyperplasia was less.A small amount of muscle regeneration was observed on day 28 after operation.(4)The results show that the methacrylated dermal extracellular matrix hydrogel can promote wound skin healing and muscle tissue regeneration in rats with abdominal wall defect.
3.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
4.Effect of Yishen Tongluo Prescription on Sperm DNA Fragmentation Index and Sperm Mitochondrial Membrane Potential in Patients with Asymptomatic Idiopathic Asthenospermia Infertility
Gaoli HAO ; Xin HE ; Lipeng FAN ; Jianshe CHEN ; Xun LI ; Hui ZHANG ; Xiang CHEN ; Shuilin LYU ; Xiaojun FU ; Zixue SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):145-151
ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index (DFI) and sperm mitochondrial membrane potential (MMP) in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group (64 cases) and a control group (64 cases). The experimental group received Yishen Tongluo prescription, while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate, sperm progressive motility (PR), total sperm motility (PR+NP), sperm function (sperm tail hypotonic swelling rate, sperm acrosin activity), sperm DFI, and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study, and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study, including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% (9/61), higher than that in the control group at 6.67% (4/60), though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group (P<0.05). Compared with the results before treatment, sperm PR, PR + NP, sperm tail hypotonic swelling rate, sperm acrosin activity, sperm DFI, and sperm MMP were significantly improved in both groups after treatment (P<0.05), with greater improvements in the experimental group (P<0.05). However, there was no significant change in sperm concentration in either group after treatment. During the study, no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility, increase spouse pregnancy rate, enhance sperm function, and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.
5.Research progress of hydrogen sulfide in H-type hypertension
Lu-Fan SHEN ; Hong WANG ; Hong-Ying LYU ; Guan-Jun JIA ; Ming-Shuang HOU ; Lin YI
Chinese Pharmacological Bulletin 2024;40(9):1601-1607
Hydrogen sulfide(H2 S),an endogenous gas trans-mitter involved in the regulation of vascular tone,has a variety of physiological properties,such as antihypertensive,vascular re-laxation,anti-inflammatory and antioxidant potential,and plays an important role in cardiovascular regulation.Chinese scholars call essential hypertension combined with hyperhomocysteinemia(HCY≥10 μmol·L-1)as H-type hypertension.Studies have shown that H2S can antagonized hypertension and hyperhomocys-teinemia,suggesting that H2S may be a potential therapeutic tar-get for H-type hypertension.Therefore,this article briefly sum-marizes the mechanism of H2S on hypertension and homocys-teine.Homocysteine(HCY)is closely related to the occurrence and development of cardiovascular diseases.Hyperhomocysteine-mia(HCY ≥ 10 μmol·L-1)is a risk factor for coronary ath-erosclerotic heart disease,stroke,and other cardiovascular dis-eases,and Chinese scholars define primary hypertension accom-panied by hyperhomocysteinemia as H-type hypertension,which accounts for about 75%of the adult hypertensive patients in Chi-na.The treatment of H-type hypertension should simultaneously reduce blood pressure and plasma HCY levels.Studies have shown that hydrogen sulfide(H2 S)can antagonise hypertension and high HCY,suggesting that H2S may be a potential therapeu-tic target for H-type hypertension.Therefore,this paper summa-rizes the mechanism of action of H2S on hypertension and HCY.
6.Effect of ureteral wall thickness at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy
Wei PU ; Jian JI ; Zhi-Da WU ; Ya-Fei WANG ; Tian-Can YANG ; Lyu-Yang CHEN ; Qing-Peng CUI ; Xu XU ; Xiao-Lei SUN ; Yuan-Quan ZHU ; Shi-Cheng FAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1077-1081
Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.
7.Research progress on fecal incontinence in patients undergoing transanal total mesorectal excision
Ao HUANG ; Hua YANG ; Mingyang REN ; Zhenbing LYU ; Yushi FAN
Chinese Journal of Modern Nursing 2024;30(20):2789-2794
Total mesorectal excision (TME) is the gold standard for the treatment of middle and low rectal tumors. Since the first patient who underwent transanal total mesorectal excision (taTME) was reported in 2010, taTME has attracted wide attention from scholars at home and abroad. Fecal incontinence is one of the common complications after taTME, which severely affects the postoperative quality of life of patients. This paper systematically summarizes the commonly used assessment methods, current situation, influencing factors, treatment and nursing progress of postoperative fecal incontinence patients with taTME, in order to provide evidence for improving the quality of life of postoperative defecation incontinence patients with taTME.
8.Correlation between 1, 5-anhydroglucitol and mild cognitive impairment in elderly patients with type 2 diabetes mellitus
Lina WANG ; Xinju JIA ; Yuqing GUO ; Yan KANG ; Fan LIU ; Xiaojing LYU ; Huimin ZHOU
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(7):618-623
Objective:To explore the correlation between serum 1, 5-anhydroglucitol (1, 5-AG) and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes mellitus (T2DM).Methods:A total of 160 patients with T2DM aged 60-75 years old who visited the First Hospital of Hebei Medical University from May 2021 to July 2022 were selected. According to the Montreal cognitive assessment (MoCA), all patients were divided into T2DM with MCI group (T2DM+ MCI group, n=81) and T2DM without MCI group (T2DM group, n=79). All research subjects were tested for glycated hemoglobin A1c (HbA1c), serum 1, 5-AG, serum β-amyloid peptide 42 (Aβ42), and blood biochemical indicators.SPSS 25.0 statistical software was used for data analysis. The t test, Mann-Whitney U test and χ2 test were used to compare the two groups. Binary Logistic regression analysis was used to examine the relevant influencing factors. Results:(1) Compared with T2DM group, patients in T2DM+ MCI group had significantly higher age, systolic pressure and HbA1c(all P<0.05).The level of 1, 5-AG in T2DM+ MCI group was significantly lower than that in T2DM group( (15.65±2.56 )μg/mL, (18.17±3.72 )μg/mL, P<0.01), and the level of Aβ42 was higher than that of T2DM group (2.95 (3.36) pg/mL, 1.91 (2.48) pg/mL, P<0.05). (2) Binary Logistic regression analysis results showed that HbA1c( β=0.230, OR=1.259, 95% CI=1.010-1.568, P=0.040) and Aβ42( β=0.188, OR=1.206, 95% CI=1.033-1.409, P=0.018) were the independent risk factors for MCI in elderly patients with T2DM, while 1, 5-AG ( β=-0.240, OR=0.786, 95% CI=0.698-0.886, P<0.001) was the protective factor for MCI. Conclusion:There is a positive correlation between serum 1, 5-AG and cognitive function, and the decrease of 1, 5-AG level was associated with the increased risk of MCI in elderly patients with T2DM.
9.Family rehabilitation based on digital health management can help elderly diabetes patients with sarcopenia
Yinghua LYU ; Wei WEI ; Wenzhen HUANG ; Fan ZHOU ; Jie WANG ; Huihui MA ; Huijuan YUAN
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(5):443-447
Objective:To observe any effect of family rehabilitation interventions based on digital health management on elderly type 2 diabetes mellitus (T2DM) patients with sarcopenia.Methods:One hundred elderly T2DM patients with sarcopenia who had been discharged from hospital after treatment were divided into an observation group and a control group, each of 50. Both groups continued the diet control and training begun during their hospitalization, but the observation group was additionally provided with family rehabilitation based on digital health management. Before and after 3 months, the glucose and lipid metabolism and sarcopenia of both groups were evaluated with related symptom indexes, and their levels of diabetes self-management were compared.Results:Significant improvement was observed in both groups, but the average glucose and lipid metabolism indexes and sarcopenia-related symptom indexes of the observation group were significantly better than the control group′s averages. Their diabetes self-management was also significantly superior.Conclusion:Family rehabilitation based on digital health management can significantly improve glucose and lipid metabolism and muscle mass in elderly T2DM patients with sarcopenia. Such intervention is worthy of promotion and application in clinical practice.
10.Differential gene expression profiling between subcutaneous fat and orbital septum fat
Wei LYU ; Yanlong LIU ; Enpeng XIE ; Chuan LI ; Fan YANG ; Shirong LI
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(5):506-511
Objective:To investigate the differential gene expression profiling between subcutaneous fat (SF) and orbital septum fat (OF).Methods:Six samples of SF tissue were collected from patients undergoing abdomen or thigh liposuction, and six samples of OF tissue were collected from patients undergoing double eyelid or pouch surgery in Chongqing Xing Rong Plastic Surgery Hospital from May 2022 to June 2022. Transcriptional characteristics of SF and OF were compared by RNA sequencing. The gene expression differences between SF and OF were analyzed by bioinformatics methods. The differences in gene expression were verified by real-time quantitative PCR (qRT-PCR).Results:Principal component analysis (PCA) showed the SF and OF groups were obviously separated as two independent gene clusters. The volcano plot analysis displayed the upregulated genes (such as FOXL2 and FOXL2NB), or the downregulated genes (such as DEFB132 and HOXB3) in SF group compared to those in OF group. Besides, the protein-protein interaction (PPI) network revealed the top 3 upregulated hub genes in SF group (MYH7, TCAP and MYL2) and in OF group (SOX9, WNT1 and WNT2). Heatmap analysis based on the above PPI showed that the two groups of upregulated genes were clustered and separated obviously. In addition, the signaling pathway analysis revealed that cardiomyopathy, muscle contraction and AMPK pathway were enriched in the SF group, while Wnt singling and cancer-related pathway were enriched in OF group. Finally, the qRT-PCR showed that SOX9 ( P<0.001) and WNT2 ( P<0.001) were upregulated, while DEFB132 ( P<0.001) and HOXB3 ( P<0.01) were downregulated in OF group compared to SF group, respectively. Conclusions:Compared to SF group, SOX9 and WNT2 are regulated, while DEFB132 and HOXB3 are downregulated in OF group. The differentially expressed genes in OF may be the key factors mediating its unique physiological features.


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