1.Rehmanniae Radix Iridoid Glycosides Protect Kidneys of Diabetic Mice by Regulating TGF-β1/Smads Signaling Pathway
Hongwei ZHANG ; Ming LIU ; Huisen WANG ; Wenjing GE ; Xuexia ZHANG ; Qian ZHOU ; Huani LI ; Suqin TANG ; Gengsheng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):56-66
ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides (RIG) on the kidney tissue of streptozotocin (STZ)-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group, and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model, metformin (250 mg·kg-1), catalpol (100 mg·kg-1), low-dose RIG (RIG-L, 200 mg·kg-1) and high-dose RIG (RIG-H, 400 mg·kg-1) groups (n=11). Mice in each group were administrated with corresponding drugs, while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention, an oral glucose tolerance test (OGTT) was performed, and the area under the curve (AUC) was calculated. After mice were sacrificed, both kidneys were collected. The body weight, kidney weight, and fasting blood glucose (FBG) were measured. Biochemical assays were performed to measure the serum levels of triglycerides (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). Enzyme-linked immunosorbent assay (ELISA) was employed to determine the serum level of fasting insulin (FINS), and the insulin sensitivity index (ISI) and homeostatic model assessment for insulin resistance (HOMA-IR) were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method (IHC) was employed to assess the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), and collagen-3 (ColⅢ) in the kidney tissue. The protein levels of TGF-β1, cell signal transduction molecule 3 (Smad3), matrix metalloproteinase-9 (MMP-9), and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group, the model group showcased decreased body weight and ISI (P<0.01), increased kidney weight, FBG, AUC, FINS, HOMA-IR, TC, TG, SCr, and BUN (P<0.01), glomerular hypertrophy, capsular space narrowing, and collagen deposition in the kidney, up-regulated protein levels of IL-1, IL-6, TNF-α, TGF-β1, ColⅢ, and Smad3 (P<0.01), and down-regulated protein level of MMP-9 (P<0.01) in the kidney tissue. Compared with the model group, the treatment groups had no significant difference in the body weight and decreased kidney weight (P<0.05, P<0.01). The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin, catalpol, and RIG-L groups after treatment for 6-8 weeks (P<0.01). The AUC in the RIG-L, RIG-H, and metformin groups decreased (P<0.05, P<0.01). The levels of TC, SCr, and BUN in the serum of mice in each treatment group became lowered (P<0.05, P<0.01). The level of TG declined in the RIG-L, RIG-H, and metformin groups (P<0.05, P<0.01). The serum level of FINS declined in the catalpol, RIG-L, and metformin groups (P<0.01). Compared with the model group, the treatment groups showed decreased HOMA-IR (P<0.01), increased ISI (P<0.01), alleviated pathological changes in the kidney tissue, and down-regulated expression of IL-1 and TGF-β1. In addition, the protein levels of IL-6, TNF-α, and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated (P<0.05, P<0.01), and the protein levels of IL-6, TNF-α, and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β1, Smad3, and ColⅢ in the RIG-H and metformin groups were down-regulated (P<0.01). Compared with that in the model group, the protein level of MMP-9 was up-regulated in each treatment group (P<0.01). ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β1/Smads signaling pathway.
2.Effects of KHSRP targeting JAK1/STAT3 signaling pathway on the malignant biological behavior of the adenocarcinoma of esophagogastric junction
ZHANG Haifenga ; WANG Mengyaob△ ; WANG Xiaolonga ; LIU Yangyangb ; LI Lia,b ; WEI Haitaoa
Chinese Journal of Cancer Biotherapy 2025;32(1):38-47
[摘 要] 目的:探讨KH型剪切调节蛋白(KHSRP)靶向调控JAK1/STAT3信号轴对食管胃结合部腺癌(AEG)细胞增殖、迁移和侵袭及移植瘤生长与肺转移的影响。方法:收集2017年1月至2018年12月间在淮河医院确诊的64例AEG组织和癌旁组织标本及临床资料,采用免疫组化法观察AEG组织和癌旁组织中KHSRP的表达水平。qPCR法检测AEG细胞OE-19、TE-7、BIC-1、FLO-1、SK-GT-4、BE-3与正常食管上皮细胞Het-1A中KHSRP的表达差异。通过慢病毒载体对KHSRP进行敲减和过表达处理,分别转染OE-19与TE-7细胞、FLO-1与SK-GT-4细胞,实验分为sh-NC组、sh-KHSRP组和Vector组、KHSRP过表达组(KHSRP组)。采用qPCR法检测敲减或过表达效率,CCK-8法、Transwell小室法分别检测敲减或过表达KHSRP对AEG细胞增殖、迁移和侵袭的影响。构建小鼠异种移植瘤和肺转移模型,观察KHSRP对移植瘤体内生长和转移的作用。WB法验证KHSRP靶向JAK/STAT信号通路。细胞拯救实验验证KHSRP是否通过调节JAK1/STAT3信号通路促进AEG细胞的恶性进程。结果:与癌旁组织相比,AEG组织中KHSRP表达水平显著增高(P < 0.05或P < 0.01)。细胞功能实验分析显示,KHSRP过表达在体外均显著促进AEG细胞增殖、迁移和侵袭(P < 0.05或P < 0.01)。动物实验结果显示,KHSRP在裸鼠体内具有促进AEG细胞移植瘤生长与肺转移的作用(P < 0.05或P < 0.01)。在敲减KHSRP后,JAK/STAT信号通路中JAK1、STAT3磷酸化水平均明显降低,过表达KHSRP后情况则均反之(P < 0.05或P < 0.01)。细胞拯救实验显示,KHSRP可以逆转敲减JAK1/STAT3对细胞增殖、迁移和侵袭的抑制作用(P < 0.05或P < 0.01)。结论:KHSRP通过激活JAK1/STAT3信号通路调控AEG细胞转移的恶性进程,KHSRP有望成为AEG临床治疗的潜在靶点。
3.Analysis of the effect of fudosteine on induced sputum components in patients with stable neutrophil-dominated COPD
Zhanbo LI ; Kaifeng DU ; Zhilong JIANG ; Jiameng GAO ; Mengjie CHEN ; Yuan MA ; Zhihong CHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):362-369
AIM:To observe the effect of fudostei-ne on induced sputum cell components and lung function in patients with stable neutrophil-dominat-ed COPD.METHODS:From October 2019 to Octo-ber 2022,53 patients with stable COPD were select-ed and divided into fudosteine group and placebo group.The placebo group was treated with routine treatment,and the fudosteine group was treated with fudosteine on the basis of routine treatment.The two groups were treated for 6 months.The clinical symptoms[Saint George's Respiratory Questionnaire(SGRQ),COPD Assessment Test(CAT)and Modified British Medical Research Council Dys-pnea scale(MMRC),Breathlessness,Cough,and Sputum Scale(BCSS)],lung function index,induced sputum cytology analysis and other related exami-nation results were recorded in detail before and after treatment.RESULTS:(1)Compared with the baseline,the forced expiratory volume in one sec-ond(FEV1),forced vital capacity(FVC),and the ra-tio of FEV1 to FVC(FEV1/FVC)of the two groups were improved after treatment,and the differenc-es were statistically significant(P<0.05).However,after treatment,there was no significant difference in pulmonary function between the two groups ex-cept for the percentage of carbon monoxide diffu-sion in the predicted value(DLCO%pre)(DLCO%pre in the fudosteine group was higher than that in the placebo group).(2)After treatment,the total num-ber of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group.Compared with the number of cells in each component at baseline,the total num-ber of induced sputum cells and neutrophil count in the fudosteine group were significantly lower(P<0.05).CONCLUSION:Fudosteine treatment in pa-tients with stable neutrophil-dominated COPD can improve lung function,reduce the total number of induced sputum cells and the total number of neu-trophils,thereby improving airway inflammation.
4.Spatial Dynamics of Chickenpox Outbreaks in Rapidly Developing Regions:Implications for Global Public Health
Wang LI ; Wang MIAOMIAO ; Xu CHENGDONG ; Wang PEIHAN ; You MEIYING ; Li ZIHAN ; Chen XINMEI ; Liu XINYU ; Li XUDONG ; Wang YUANYUAN ; Hu YUEHUA ; Yin DAPENG
Biomedical and Environmental Sciences 2024;37(7):687-697
Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.
5.Evaluation of the effect of the"tertiary hospital-community integrated"TCM-based management and treatment program in 60 patients with diabetic kidney disease
Xueying HUANG ; Ning ZHANG ; Kaifeng SHI ; Pu YAN ; Xiangyu LI ; Qian ZHANG ; Xin WANG ; Guozhao YAO ; Ying HUANG ; Tongxia LI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(1):107-115
Objective We aimed to observe the effect of the traditional Chinese medicine(TCM)-based"tertiary hospital-community integrated"treatment program in patients with diabetic kidney disease.Methods A total of 126 patients from the Jiangtai and Cuigezhuang Communities in Chaoyang District were randomly divided into the experimental group and the control group(n=63 patients per group).In the experimental group,the"tertiary hospital-community integrated"treatment program was implemented(including TCM differentiated health preservation,chronic disease management,comprehensive diagnosis and treatment program of integrated Chinese and Western medicine),while in the control group,the existing chronic disease diagnosis,treatment,and management program in the community was implemented(including chronic disease management with regular follow-ups,diagnosis and treatment program of Western medicine).The observation period was 6 months,with 3 months as a course of treatment.The 24 h urine total protein level(24 hUTP),the serum level of creatinine(Scr),and the estimated glomerular filtration rate(eGFR)were compared between the two groups,as well as the effective rates of 24 hUTP,Scr,and eGFR,the rate of achieving standard glucose levels and normal lipid metabolism,including low-density lipoprotein-cholesterol(LDL-C),triglyceride(TG),and glycosylated hemoglobin(GHB),the level of patients'self-management,and the medical service in utilization.Results There were 120 patients included for analysis(60 in the experimental group and 60 in the control group).The difference in 24 hUTP was significantly different(P<0.05),while Scr and eGFR were not statistically different between the experimental and control groups after 3 months of treatment.The differences in 24 hUTP,Scr,and eGFR were statistically significant after 6 months(P<0.05).After 6 months of treatment in both groups,the effective rates of 24 hUTP,Scr,and eGFR were higher in the experimental group than in the control group(78.3%,48.3%,and 50.0%in the experimental group and 35.0%,18.3%,and 15.0%in the control group,respectively)(P<0.05);after 6 months,the LDL-C,TG,and GHB qualified rates were higher in the experimental group than in the control group(75.0%,83.3%,and 71.7%in the experimental group and 56.7%,63.3%,and 46.7%in the control group,respectively;P<0.05);comparing the self-management levels of the two groups after 3 and 6 months of treatment,the total self-management score and the total self-efficacy score were both higher in the experimental group than in the control group(P<0.05);comparing the time of hospitalization and hospitalization costs of the two groups 6 months after enrollment,the time of hospitalization and hospitalization costs were lower in the experimental group(P<0.05).Conclusion The"tertiary hospital-community integrated"TCM-based treatment program improves renal function,glucose and lipid metabolism,and patients'self-management;it can reduce the economic burden of families,save medical resources,and improve the utilization of medical services.
6.Efficacy and safety comparison of lacosamide and carbamazepine in the treatment of adult patients with newly diagnosed epilepsy
Xiaqing GUO ; Guofei LI ; Yuhua SUN ; Donglin ZHENG
China Pharmacy 2024;35(4):464-467
OBJECTIVE To compare the efficacy and safety of lacosamide (LCM) and carbamazepine (CAR) as monotherapy in the treatment of adult patients with newly diagnosed epilepsy. METHODS By methods of retrospective analysis, 84 adult patients with newly diagnosed epilepsy, were admitted to the Department of Neurology, Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022, were divided into the control group (40 cases, receiving CAR treatment) and the observation group (44 cases, receiving LCM treatment) according to different medication regimens. Total response rate, epilepsy seizure frequency, blood lipid levels, and the occurrence of adverse events (AEs) of patients were compared between the 2 groups. RESULTS In the first month after treatment, there was no statistically significant difference in the total response rate between the observation group (63.64%) and the control group (55.00%, P>0.05); the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment (P<0.05), but there was no statistically significant difference between 2 groups (P>0.05). In the third month after treatment, the total response rate of the observation group (90.91%) was significantly higher than control group (67.50%, P<0.05); the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment, and the observation group was significantly lower than the control group (P<0.05). In the third month after treatment, the levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholestrol (LDL-C) in the control group and the level of LDL-C in the observation group were significantly higher than before treatment, and the levels of TC, TG and LDL-C in the observation group were significantly lower than those in the control group (P<0.05). There was no statistically significant difference in the incidence of AEs between the observation group (15.91%) and the control group (17.50%, P>0.05). CONCLUSIONS Both LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults, which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile, LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults, and its impact on the patient’s blood lipid is smaller than CAR.
7. Analysis of the effect of fudosteine on induced sputum components in patients with stable neutrophil-dominated COPD
Zhanbo LI ; Kaifeng DU ; Zhilong JIANG ; Jiameng GAO ; Mengjie CHEN ; Yuan MA ; Zhihong CHEN ; Zhanbo LI ; Kaifeng DU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):362-369
AIM: To observe the effect of fudosteine on induced sputum cell components and lung function in patients with stable neutrophil-dominated COPD. METHODS: From October 2019 to October 2022, 53 patients with stable COPD were selected and divided into fudosteine group and placebo group. The placebo group was treated with routine treatment, and the fudosteine group was treated with fudosteine on the basis of routine treatment. The two groups were treated for 6 months. The clinical symptoms [Saint George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Modified British Medical Research Council Dyspnea scale (MMRC), Breathlessness, Cough, and Sputum Scale (BCSS)], lung function index, induced sputum cytology analysis and other related examination results were recorded in detail before and after treatment. RESULTS: (1) Compared with the baseline, the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC) of the two groups were improved after treatment, and the differences were statistically significant (P<0.05). However, after treatment, there was no significant difference in pulmonary function between the two groups except for the percentage of carbon monoxide diffusion in the predicted value (DLCO%pre) (DLCO%pre in the fudosteine group was higher than that in the placebo group). (2) After treatment, the total number of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group. Compared with the number of cells in each component at baseline, the total number of induced sputum cells and neutrophil count in the fudosteine group were significantly lower (P< 0.05). CONCLUSION: Fudosteine treatment in patients with stable neutrophil-dominated COPD can improve lung function, reduce the total number of induced sputum cells and the total number of neutrophils, thereby improving airway inflammation.
8.Preparation and characterization of curcumin nanomicelles and evaluation of in vitro hepatoprotective activity against alcohol liver disease
Luhui LI ; Guangping GENG ; Lei XU ; Zhikun ZHANG ; Xiaohui PU
China Pharmacy 2024;35(10):1203-1208
OBJECTIVE To prepare and characterize curcumin nanomicelles (hereinafter referred to as Cur/mPEG-PBLA micelles), and to evaluate the in vitro hepatoprotective activity against alcohol liver disease (ALD). METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly(ethylene glycol)-poly(β-benzyl-L-aspartate) (mPEG-PLGA) as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed, and particle size, polydispersity index, Zeta potential, encapsulation efficiency and drug loading content were all detected. The in vitro release, pH stability, thermal stability, dilution stability, storage stability, plasma stability tests, and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects, Cur reference solution as reference, to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light, with a spherical shape and uniform distribution. The average particle size was about 140 nm, and the polydispersity index was less than 0.3. Zeta potential was (-8.15±0.05) mV; the encapsulation efficiency was (73.26±3.16)%, and the drug loading content was (4.87± 0.42)%. The cumulative release of Cur reference substance was close to 80% at 10 h; the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution; Cur/mPEG-PBLA micelles showed good dilution stability, storage stability and plasma stability, and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells; after 48 h of application, the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration (P<0.05). CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur, delayits degradation rate, and have better in vitro hepatoprotective activity against ALD.
9.Clinical Effectiveness and Safety of Bairui Granules (百蕊颗粒) in Treating Patients with Acute Pharyngitis with Wind-Heat Syndrome: A Multi-Center, Double-Blind, Double-Simulation, Randomized Controlled Trial
Siming LIU ; Hui ZHOU ; Qiang LI ; Min ZHOU ; Qixiang WU ; Shanjun YANG ; Jun WANG ; Jingjing YUAN ; Ying ZHANG ; Ziqi ZHU ; Jingyi HU ; Shuang WU ; Mengting LI ; Zhanfeng YAN
Journal of Traditional Chinese Medicine 2024;65(11):1139-1145
ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules (百蕊颗粒) in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter, double-blind, double-simulation, randomised controlled trial was conducted, in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited, and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group, 108 cases were orally administered with Bairui Granules plus Reyanning Granules (热炎宁颗粒) simulant, and in the control group, 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days, with a follow-up visit on the 6th day. Full analysis set (FAS) analysis and per protocol set (PPS) were used for analysis, respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment; the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment, as well as the visual analogue score (VAS) of sore throat before treatment, every day during the treatment, and follow-up on day 6, and the traditional Chinese medicine (TCM) syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6, and the changes of vital signs, blood routine, urine routine, liver functions, kidney function, the adverse events before and after the treatment were recorded, and safety analysis set (SS) was analysed. Results162 patients entered the FAS and SS analyses, and 158 cases (105 cases in the trial group and 53 cases in the control group) entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% (87/108) in the trial group and 64.81% (35/54) in the control group, and the difference between groups was statistically significant (χ2 = 5.10, P = 0.0239). PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% (84/105) in the trial group and 64.15% (34/53) in the control group, and the difference between groups was statistically significant (χ2 =4.85, P = 0.0277). FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant (P>0.05). Compared with those before treatment, the VAS scores of sore throat were lower in both groups during treatment on day 2, 3, 4, 5, and follow-up on day 6 (P<0.01), but the difference between groups at each time point was not statistically significant (P>0.05). TCM syndrome scores of both groups at the follow-up were lower than that before treatment, and those of the trial group were lower than those of the control group (P<0.01). The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group (P<0.01). There was no significant difference in blood routine, urine routine, liver function, kidney function between groups before and after treatment (P>0.05), and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome, and it could significantly improve the clinical symptoms, accelerate the disappearance time of sore throat with good safety.
10.Chinese Herbal Enema Combined with Fumigation as Adjunctive Therapy for 60 Cases of Non-dialysis Chronic Kidney Disease Patients of Stage 3-5 with Spleen-kidney Yang Deficiency and Turbid Toxin Blood Stasis Pattern:A Randomized Controlled Trial
Xueying HUANG ; Ning ZHANG ; Xiangyu LI ; Qian ZHANG ; Kaifeng SHI ; Pu YAN ; Tongxia LI
Journal of Traditional Chinese Medicine 2024;65(7):703-709
ObjectiveTo observe the clinical efficacy and safety of Chinese herbal enema combined with fumigation as adjunctive therapy for non-dialysis chronic kidney disease (CKD) patients of stage 3

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