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.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.
4.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
5.Efficacy of 450 nm blue laser with 6 o’clock positioning in the treatment of middle lobe hyperplasia of prostate
Fanzhuo TU ; Xiaohang HAO ; Yan HU ; Zunjie HU ; Song LI ; Wenju GAO ; Fei LIU ; Haoxing WANG ; Yongwei ZHAO
Journal of Modern Urology 2024;29(4):320-323
【Objective】 To investigate the efficacy and safety of 450 nm blue laser with 6 o’clock positioning in the treatment of middle lobe hyperplasia of prostate, in order to promote the clinical application of this surgery. 【Methods】 Clinical data of 20 patients with middle lobe hyperplasia of prostate treated with 450 nm blue laser with 6 o’clock positioning during Mar.and Aug.2023 were retrospectively analyzed.The operation time, postoperative bladder irrigation time, catheter indwelling time, hospital stay, and complications were recorded.The maximum urinary flow rate (Qmax), post-void residual volume (PVR), quality of life scale (QoL), international prostate symptom score (IPSS) before surgery and 1 month after surgery were compared. 【Results】 The operation time was (26.80±7.22) min, and bladder irrigation time was (20.50±1.79) h.The catheter was removed on the next day after surgery and all patients were discharged 2 days after operation.Compared to preoperative, one month after surgery, the Qmax [(7.40±1.05) mL/s vs.(19.60±1.76) mL/s] was significantly higher, PVR [(73.50±12.26) mL vs.(9.25±4.94) mL], QoL [(4.55±1.19) vs.(1.95±0.95)], and IPSS [(26.55±1.88) vs.(10.05±1.36)] were significantly lower, the differences being statistically significant (P<0.05).No complications occurred during operation and 1-month follow-up. 【Conclusion】 The 450 nm blue laser with 6 o’clock positioning is a new, safe and effective surgical treatment of middle lobe hyperplasia of prostate, which is worthy of clinical promotion and application.
6.A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement
Hua ZHENG ; Yunfei ZHI ; Lujing YING ; Lan ZHU ; Mingliang JI ; Ze LIANG ; Jiangshan WANG ; Haifeng SHI ; Weihong ZHANG ; Mengsu XIAO ; Yushi ZHANG ; Kaifeng XU ; Zhaohui LU ; Yaping LIU ; Ruiyi XU ; Huijuan ZHU ; Li WEN ; Yan ZHANG ; Gang CHEN ; Limeng CHEN
JOURNAL OF RARE DISEASES 2024;3(1):79-86
Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.
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
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.
8.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.
9.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.
10.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.

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