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.Distribution of Traditional Chinese Medicine Syndrome Elements in Different Risk Populations of Heart Failure Complicated with Type 2 Diabetes: A Retrospective Study Based on Nomogram Model and Factor Analysis
Tingting LI ; Zhipeng YAN ; Yajie FAN ; Wenxiu LI ; Wenyu SHANG ; Yongchun LIANG ; Yiming ZUO ; Yuxin KANG ; Boyu ZHU ; Junping ZHANG
Journal of Traditional Chinese Medicine 2025;66(11):1140-1146
ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine (TCM) syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this, 441 non-heart failure patients were divided into a low-risk group (325 cases) and a high-risk group (116 cases) according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information (four diagnostic methods) was collected for both groups, and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age, disease duration, coronary heart disease, old myocardial infarction, arrhythmia, absolute neutrophil count, activated partial thromboplastin time, and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the modeling group and validation group were 0.934 and 0.935, respectively. The Hosmer-Lemeshow test (modeling group P = 0.996, validation group P = 0.121) indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner, indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency (175 cases, 53.85%), dampness (118 cases, 36.31%), and heat (118 cases, 36.31%), with the primary locations in the spleen (125 cases, 38.46%) and lungs (99 cases, 30.46%). In the high-risk group, the main disease elements were yang deficiency (73 cases, 62.93%), blood stasis (68 cases, 58.62%), and heat (49 cases, 42.24%), with the primary locations in the kidney (84 cases, 72.41%) and heart (70 cases, 60.34%). ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess, with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat, related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat, related to the kidneys and heart.
3.Effect of Qigui Didang Decoction in Improving Metabolic Memory of Diabetic Nephropathy Through Sirt1/p53/NF-κB p65 Pathway
Tingting HU ; Lifei FAN ; Yuqin GUO ; Min LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):20-29
ObjectiveTo explore the effect and mechanism of Qigui Didang decoction, formulated based on the principle of Tonifying Deficiency and Unblocking Collaterals, on improving metabolic memory of db/db mice with diabetic nephropathy (DN) through silent information regulator 1 signal regulator 1 (Sirt1)/p53/nuclear factor kappa-B (NF-κB) p65 pathway. MethodsFifteen db/db mice were randomly divided into model group (10 mL·kg-1·d-1), resveratrol group (20 mg·kg-1·d-1), and Qigui Didang decoction group (3.34 g·kg-1·d-1) Another five db/m mice were selected as the normal group (10 mL·kg-1·d-1). After the intervention, the kidney weight of each group was measured, and the kidney index (KI) was calculated. Fasting blood glucose (FBG), creatinine (CRE), β2-microglobulin (β2-MG), blood urea nitrogen (BUN), and cystatin C (CysC) were measured. Renal pathology was observed by hematoxylin-eosin (HE) staining and Masson staining. The mRNA and protein expression levels of Sirt1, NF-κB, tumor suppressor gene p53, interleukin-1β (IL-1β), and cysteine aspartate protease-3 (Caspase-3) were detected using real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the normal group, the model group showed disordered renal structure, obvious renal damage, and markedly elevated levels of renal function indexes (CRE, β2-MG, BUN, and CysC) (P<0.01). The KI and blood glucose were significantly increased (P<0.01), while Sirt1 expression was markedly decreased (P<0.01). Expression levels of NF-κB p65, p53, IL-1β, and Caspase-3 were increased significantly (P<0.05). Compared with those in the model group, DN mice treated with Qigui Didang decoction exhibited significantly decreased FBG, improved renal function, and markedly decreased KI (P<0.01), along with reduced CRE, β2-MG, BUN, and CysC levels (P<0.05). Protein expression of Sirt1 was significantly upregulated (P<0.05), while that of NF-κB p65, p53, IL-1β, and Caspase-3 was markedly decreased (P<0.05). The mRNA expression levels of NF-κB p65, p53, IL-1β, and Caspase-3 were significantly decreased (P<0.05). The staining results indicate improved renal fibrosis, significantly decreased fiber deposition (P<0.05), and less inflammatory infiltration in the Qigui Didang decoction group. ConclusionThe findings suggest that Qigui Didang decoction can alleviate the metabolic memory effect of DN, thereby inhibiting renal cell apoptosis and inflammatory response in mice, and improving renal function. The mechanism of action is closely related to the Sirt1/p53/NF-κB p65 signaling pathway.
4.Survey on human T-lymphotropic virus infection among blood donors in Hunan province
Binbin ZOU ; Qing HU ; Ni SUN ; Xiangmei KANG ; Tingting HU ; Fei FAN ; Feixue ZHAO
Chinese Journal of Blood Transfusion 2025;38(8):1077-1082
Objective: To investigate the prevalence of human T-lymphotropic virus (HTLV) infection among blood donors in Hunan Province from 2022 to 2024. Methods: A total of 1 830 342 blood donors from 14 prefecture-level blood centers in Hunan Province over the past three years were screened for anti-HTLV-Ⅰ/Ⅱ using enzyme-linked immunosorbent assay (ELISA). Initially reactive samples were further tested with Line Immunoassay (LIA
)/MP-Western blot and RT-PCR nucleic acid test for confirmation. Blood donors confirmed positive for HTLV were tracked and followed up. Results: From 2022 to 2024, the initial ELISA reactive rate for anti-HTLV-I/II among blood donors in Hunan Province was 1.36 per 10 000 (249/1 830 342). The confirmed positive rate was 0.20 per 10 000 (37/1 830 342), accounting for 14.86% of the initially reactive donors. The follow-up success rate for confirmed HTLV-positive blood donors was only 18.92%, while that for HTLV-indeterminate donors was 54.17%. Conclusion: The confirmed HTLV infection rates in Yueyang, Loudi, Shaoyang, Yiyang, and Zhuzhou cities were higher than the provincial (0.20 per 10 000). Chenzhou, Yongzhou, Zhangjiajie, and Xiangxi were identified as low prevalence areas, with an infection rate of 0. The overall follow-up success rate was low, indicating significant difficulties and bottlenecks in follow-up work. The comprehensive screening for HTLV and follow-up studies in Hunan provide valuable data to further improve blood safety testing strategies and risk warning mechanisms.
5.Oncolytic Newcastle disease virus inhibits IL-6 induced migration and invasion of human glioblastoma U87MG cells
TAO Weiyi ; QIN Ying ; WU Xing ; ZHENG Tingting ; FAN Xiaohui ; LIANG Ying
Chinese Journal of Cancer Biotherapy 2024;31(1):27-31
[摘 要] 目的:探讨溶瘤新城疫病毒(NDV)对IL-6诱导的人胶质母细胞瘤U87MG细胞增殖、迁移和侵袭的作用及其可能的机制。方法:将U87MG细胞分为对照组、IL-6组、NDV组、NDV+IL-6组,其中IL-6组与NDV+IL-6组用75 ng/mL IL-6预处理1 h,其余组用DMEM预处理1 h,后分别用DMEM、75 ng/mL IL-6、1 HU NDV、1 HU NDV+75 ng/mL IL-6处理24 h。MTT法、细胞划痕实验和Transwell侵袭实验分别检测IL-6、NDV对U87MG细胞增殖、迁移和侵袭的影响,WB法检测各组细胞JAK2、p-JAK2、STAT3、p-STAT3和MMP2蛋白的表达水平。结果:与对照组相比,IL-6组细胞迁移率显著升高(P<0.05),侵袭细胞数目显著增多(P<0.01);与IL-6组相比,NDV+IL-6组U87MG细胞增殖率显著降低(P<0.05),细胞迁移率和侵袭细胞数目均显著降低(均P<0.01)。WB实验结果显示,与对照组相比,IL-6组p-STAT3/STAT3比值显著升高(P<0.01),NDV组p-JAK2/JAK2、p-STAT3/STAT3比值显著降低(P<0.05,P<0.01),MMP-2蛋白表达量显著降低(P<0.01);与IL-6组相比,NDV+IL-6组p-STAT3/STAT3比值、MMP-2蛋白表达量均显著降低(均P<0.05)。结论:NDV能抑制IL-6对人脑胶质瘤U87MG细胞迁移和侵袭的诱导作用,其机制可能与JAK2/STAT3信号通路的参与调控有关。
6.An accurate diagnostic approach for urothelial carcinomas based on novel dual methylated DNA markers in small-volume urine.
Yucai WU ; Di CAI ; Jian FAN ; Chang MENG ; Shiming HE ; Zhihua LI ; Lianghao ZHANG ; Kunlin YANG ; Aixiang WANG ; Xinfei LI ; Yicong DU ; Shengwei XIONG ; Mancheng XIA ; Tingting LI ; Lanlan DONG ; Yanqing GONG ; Liqun ZHOU ; Xuesong LI
Chinese Medical Journal 2024;137(2):232-234
7.HIV-1 molecular transmission network among men who have sex with men in Shaoxing City
HE Tingting ; CAO Dongqing ; LIN Jiafeng ; JIANG Zhuojing ; ZHANG Jiafeng ; FAN Qin
Journal of Preventive Medicine 2024;36(7):571-575,579
Objective:
To investigate the molecular transmission network characteristics of HIV-1 among men who have sex with men (MSM) in Shaoxing City, Zhejiang Province, so as to provide insights into AIDS prevention and control among MSM.
Methods:
Newly reported HIV/AIDS cases among MSM in Shaoxing City were selected from January 2021 to September 2023. Plasma samples before the antiviral treatment were collected. The HIV-1 pol gene was amplified using reverse transcription PCR and nested PCR to construct phylogenetic trees for gene subtype analysis. The HIV-TRACE method was used to construct a molecular transmission network with a genetic distance of 1.5% to analyze clustering and the characteristics of cases within molecular clusters.
Results:
A total of 216 HIV/AIDS cases among MSM were included, and 179 qualified sequences were obtained. The predominant HIV-1 subtypes were CRF07_BC and CRF01_AE, with 95 and 66 cases, respectively. At 1.5% genetic distance, 20 molecular clusters were formed, with 61 nodes and 58 edges. A total of 61 sequences were connected to the transmission network (34.08%). HIV/AIDS cases among MSM from all the counties (cities, districts) in Shaoxing City were included in the network. There was the largest molecular cluster with ≥10 nodes, involving 12 cases from five counties (cities, districts), 3 medium-sized molecular clusters with 4 to 5 nodes, and the 16 small-sized molecular clusters with 2 or 3 nodes. Seven cases with high risk of transmission, each with ≥4 edges, were all CRF07_BC subtypes. Among them, two cases were from the large molecular cluster, and five cases were from the same molecular cluster composed of cases from Shengzhou City and Xinchang County.
Conclusions
The predominant HIV-1 subtypes among MSM in Shaoxing City were CRF07_BC and CRF01_AE. There was cross-regional HIV transmission, and potential transmission risk might exist in Shengzhou City and Xinchang County.
8.Clinical characteristics and related factors of patients with schizophrenia in different ages of onset
Fan YANG ; Peilin XU ; Yueqin HUANG ; Zhaorui LIU ; Tingting ZHANG ; Yanling HE ; Jie ZHANG ; Yuandong GONG ; Yan LIU ; Bo LIU ; Lesheng ZHAO ; Guoping WU ; Min LIU ; Yanjun WANG ; Jicai WANG ; Changqing GAO ; Jin LU
Chinese Mental Health Journal 2024;38(1):16-24
Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.
9.Pharmacodynamic Comparative of the Novel Huoxue Plaster and the Original Powder in Treating Chronic Soft Tissue Injury
Fanghao ZHENG ; Tingting ZHAO ; Huana FAN ; Yanfen CHEN
Chinese Journal of Modern Applied Pharmacy 2024;41(4):496-503
OBJECTIVE
To compare the efficacy of the novel Huoxue plaster and the original powder in the treatment of chronic soft tissue injury, and to provide experimental basis for the development and clinical application of hospital preparations.
METHODS
According to the different drug administration, mice were assigned to the blank group, the matrix group, the positive control group(voltaren group), the original powder raw product group, the original powder product group and the novel plaster group respectively. The writhing inhibition rate, licking time, analgesic rate and pain threshold were measured by the writhing test, formaldehyde pain test, electrical stimulation test and hot plate test. The purpose of these was to assess disparities in the drugs for analgesic purposes. The mice ear swelling test and capillary permeability test were used to determine the swelling degree, swelling inhibition rate and exudation inhibition rate to compare the differences in anti-inflammatory effects. A rat model of chronic soft tissue injury was established. The changes of calf circumference, soft tissue injury appearance score, hemorheology and histopathological observation and inflammatory factor content were compared before and after the reform of prescription and dosage form.
RESULTS
The novel Huoxue plaster had a significant inhibitory effect on the inflammatory pain induced by acetic acid and formaldehyde in mice, and there was no significant difference compared with the original powder. The analgesic effect of 60 min after administration was better than that of 90 min and 120 min after administration, and there was no significant difference compared with the original powder. The novel Huoxue plaster and the original powder had no significant effect on hot plate pain threshold. The novel Huoxue plaster had a significant anti-inflammatory effect, which could reduce the degree of ear swelling induced by xylene and reduce the inflammatory exudation of capillaries induced by acetic acid, and there was no significant difference compared with the original powder. The novel Huoxue plaster could significantly reduce the circumference and injury symptom index of the swollen leg in rats with chronic soft tissue injury, improve blood circulation and histomorphology, and significantly reduce the contents of PGE2, TNF-α and IL-1β in the injured soft tissue, and there was no significant difference compared with the original powder.
CONCLUSION
The novel Huoxue plaster has significant analgesic and anti-inflammatory effects, and can be used to treat chronic soft tissue injury. The efficacy of the novel Huoxue plaster is basically the same as that of the original powder.
10.Application effect of multimodal exercise on enteral nutrition during radiotherapy in patients with esophageal cancer complicating diabetes
Jufen FAN ; Xiaoying SHEN ; Xiaowei FU ; Tingting HUANG ; Weihong FANG
Chongqing Medicine 2024;53(5):748-753
Objective To explore the effect of multimodal exercise combined with enteral nutrition dur-ing radiotherapy in the patients with esophageal cancer complicating diabetes.Methods A total of 52 patients with esophageal cancer complicating diabetes in Zhejiang Provincial Tumor Hospital from January to Decem-ber 2021 were selected as the study subjects and divided into the control group(n=27)and intervention group(n=25)by using the random number table method.The control group implemented the routine exercise scheme,while the intervention group was given the multimodal exercise intervention on the basis of routine exercise.The blood glucose metabolism indicators,related biochemical indicators during radiotherapy and the incidence rate of adverse events during exercise were compared between the two groups.Results The levels of fasting blood glucose,random blood glucose and blood glucose before sleep in the intervention group during radiotherapy were(7.79±1.61)mmol/L,(9.47±1.77)mmol/L and(9.97±3.02)mmol/L,which were lower than(11.84±3.47)mmol/L,(14.18±5.42)mmol/L and(14.62±3.83)mmol/L in the control group with statistically significant differences(P<0.05).During the radiotherapy period,the levels of albumin,total protein and prealbumin in the intervention group were(37.96±2.13)g/L,(68.13±5.02)g/L and(232.89±41.11)g/L,which were lower than(36.05±2.89)g/L,(64.96±5.95)g/L and(207.76±47.59)g/L in the control group with statistically significant differences(P<0.05).The incidence rates of adverse e-vents such as falls,hypoglycemia and accidental extubation during multimodal exercise in the intervention group were lower than those in the control group,and the differences were statistically significant(P<0.05).Conclusion The multimodal exercise could significantly improve the nutritional status during radiotherapy in the patients with esophageal cancer complicating diabetes,stabilize the blood glucose level of the patients,and has good feasibility and safety.


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