1.Polydatin Delays Progression of Colitis-associated Colorectal Cancer by Modulating IL-17A/Wnt/β-catenin Signaling Pathway
Jie LIU ; Mengmeng LYU ; Yanfei HONG ; Xinmei NAN ; Jialong SU ; Huachen LIU ; Qing WANG ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):144-154
ObjectiveTo investigate the effects and underlying mechanisms of polydatin in delaying the progression of colitis-associated colorectal cancer (CAC) by constructing an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC mouse model and conducting in vitro experiments. MethodsFifty-four male C57BL/6J mice were randomly divided into normal, model, and polydatin groups (0.045 g·kg-1). The CAC mouse model was established using AOM/DSS, and samples were collected at 4, 7, and 10 weeks. Body weight change rate, disease activity index (DAI), and tumor formation were assessed. Hematoxylin-eosin (HE) staining was used to observe pathological injury in intestinal tissues. Immunohistochemistry (IHC) was performed to detect zonula occludens-1 (ZO-1) expression in colonic tissues, and Western blot was used to detect the expression of E-cadherin, N-cadherin, and Vimentin in colonic epithelial cells. Real-time PCR was used to measure mRNA expression of interleukin-17A (IL-17A), Wnt3a, β-catenin, T cell factor 1 (Tcf1), E-cadherin, N-cadherin, and Vimentin in colonic tissues. Flow cytometry was used to analyze the proportion of CD8+T cells and the expression of exhaustion-related molecules in tumors. Human colon cancer DLD-1 cells were cultured in a polydatin-containing medium, and wound healing assays were performed to observe migration changes. Real-time PCR was used to detect mRNA expression of interleukin-17 receptor A (IL-17RA), Wnt3a, β-catenin, Tcf1, E-cadherin, N-cadherin, and Vimentin in DLD-1 cells. ResultsCompared with the normal group, the model group at all three time points showed significantly decreased body weight change rate (P<0.01), significantly shortened colon length (P<0.01), and markedly increased DAI scores (P<0.01). HE staining revealed significant inflammatory cell infiltration in the submucosa of the colon in the model group, accompanied by epithelial dysplasia. ZO-1 expression in colonic tissues was significantly reduced (P<0.01). The mRNA expression of the pro-inflammatory factor IL-17A and key molecules of the Wnt/β-catenin pathway (Wnt3a, β-catenin, Tcf1) was significantly elevated (P<0.05). The mRNA and protein expression of epithelial-mesenchymal transition (EMT) markers N-cadherin and Vimentin was significantly upregulated (P<0.05), while E-cadherin expression was significantly downregulated (P<0.05). The proportion of tumor-infiltrating CD8+T cells expressing immunosuppressive molecules (TIM-3, LAG-3, PD-1) was significantly increased (P<0.05). Compared with the model group, the polydatin group showed significant improvement in body weight and DAI score (P<0.01), as well as recovery of colon length and tissue injury. ZO-1 expression in colonic tissue was significantly increased (P<0.01), while IL-17A, Wnt3a, β-catenin, Tcf1, N-cadherin, and Vimentin expression levels were significantly decreased (P<0.05), and E-cadherin expression was significantly increased (P<0.01). Tumor-infiltrating CD8+ T cells expressing immunosuppressive molecules were significantly reduced (P<0.05). In vitro experiments showed that polydatin significantly inhibited migration of DLD-1 cells (P<0.01) and reversed the upregulation of IL-17RA, Wnt3a, β-catenin, N-cadherin, and Vimentin mRNA, as well as the downregulation of E-cadherin mRNA (P<0.05). ConclusionPolydatin inhibits IL-17A secretion and IL-17RA expression, improves the immune microenvironment, blocks activation of the Wnt/β-catenin signaling pathway, suppresses EMT markers (N-cadherin and Vimentin), and restores tight junction protein expression in intestinal epithelial cells, thereby delaying the progression from colitis to colorectal cancer in mice.
2.Molecular Mechanism of Gypenoside L Inducing Ovarian Cancer Cell Apoptosis by Regulating NUF2 and Influencing Magnesium Homeostasis
Yang HONG ; Di ZHANG ; Yuanguang DONG ; Jiaxin WANG ; Lu PAN ; Lijiang ZHOU ; Mingdian YUAN ; Qun WANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):155-165
ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component (NUF2) and magnesium homeostasis in ovarian cancer cell apoptosis, as well as the regulatory mechanism of gypenoside L (Gyp-L) on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group, a low-concentration Gyp-L group (50 µmol·L-1), a high-concentration Gyp-L group (100 µmol·L-1), and a cisplatin (15 µmol·L-1) group. The migration, proliferation, and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays, clonal experiments, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus (GEO) database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes (STRING) database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource (TIMER) database, and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis (GEPIA) database. The mRNA expression levels of NUF2, magnesium homeostasis-related indicators, such as magnesium transporter 1 (MAGT1), non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), NIPA-like domain containing 1 (NIPAL1), as well as apoptosis-related indicators B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in OVCAR3 cells, were detected by real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of NUF2, MAGT1, NIPA1, NIPAL1, Bcl-2, and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed, and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning, TUNEL staining, Real-time PCR, and ProteinSimple WES. Finally, the Mg2+ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis (P<0.05). Overexpression of NUF2 markedly increased the expression levels of MAGT1, NIPA1, NIPAL1, and Bcl-2, while reducing the expression level of Bax (P<0.05). It also significantly elevated intracellular Mg2+ content and protein synthesis efficiency and simultaneously inhibited apoptosis (P<0.05). Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2, downregulating the expression levels of NUF2, MAGT1, NIPA1, NIPAL1, and Bcl-2 (P<0.05), while upregulating the expression level of Bax (P<0.05). ConclusionGyp-L can inhibit the occurrence of ovarian cancer, and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.
3.Expert consensus on intraoperative repositioning for patients with spine fracture and dislocation (version 2025)
Dongmei BIAN ; Ke SUN ; Ningbo CHEN ; Caixia BAI ; Miao WANG ; Yafeng QIAO ; Fei WANG ; Hong WANG ; Feng TIAN ; Mei YAN ; Meng BAI ; Linjuan ZHANG ; Liyan ZHAO ; Yaqing CUI ; Xue JIANG ; Leling FENG ; Ning NING ; Junqin DING ; Lan WEI ; Yonghua ZHAI ; Yu ZENG ; Zengmei ZHANG ; Jiqun HE ; Fenggui BIE ; Hong CHEN ; Zengyan WANG ; Li LI ; Li ZHANG ; Yaying ZHOU ; Bing SHAO ; Ying WANG ; Caixia XIE ; Yanfeng YAO ; Jingjing AN ; Wen SHI ; Xiongtao LIU ; Xiaoyan AN ; Ning NAN ; Lan LI ; Xiaohui GOU ; Qiaomei LI ; Xiuting WU ; Yuqin ZHANG ; Jing LIU ; Fusen XIANG ; Xu XU ; Na MEI ; Jiao ZHOU ; Shan FAN ; Qian WANG ; Shuixia LI
Chinese Journal of Trauma 2025;41(2):138-147
Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.
4.Periodontal health status and associated factors in community-managed patients with type 2 diabetes mellitus in Nanjing
Hao XU ; Nan ZHOU ; Chenchen WANG ; Yijia CHEN ; Yi ZHANG ; Xin HONG
Chinese Journal of Stomatology 2025;60(9):997-1007
Objective:To investigate the prevalence, severity, and influencing factors of chronic periodontitis in patients with type 2 diabetes mellitus (T2DM) in Nanjing.Methods:From June to August 2022, by using a multi-stage stratified cluster random sampling method, a total of 1 477 community-dwelling T2DM patients aged 35 years and older were selected and included from the National Essential Public Health Services Program for T2DM health management. Physical examinations, laboratory tests, and questionnaire surveys were conducted. Study participants were divided into chronic periodontitis group and non-chronic periodontitis group. The chronic periodontitis group was defined as having interproximal clinical attachment loss (CAL) detected at least at two non-adjacent sites, or having buccal/lingual CAL≥3 mm at least at two sites with probing depth (PD)≥3 mm, while excluding CAL caused by non-periodontal reasons. The remaining participants were classified as the non-chronic periodontitis group. In the chronic periodontitis group, patients who had PD≥6 mm at least at two sites with CAL≥5 mm were defined as severe periodontitis, with remaining cases classified as mild-to-moderate periodontitis.Results:The prevalence of chronic periodontitis among T2DM patients was 70.1% (962/1 373), with mild to moderate and severe periodontitis prevalence rates of 62.4% (857/1 373) and 7.6% (105/1 373), respectively. After complex weighted processing, the prevalence of chronic periodontitis in T2DM patients was 67.9%, with mild to moderate and severe periodontitis prevalence rates of 61.2% and 6.7%, respectively. Multivariate logistic regression analysis showed that after adjusting all covariates, compared with mental workers, the risk of chronic periodontitis was significantly higher in retired people ( OR=1.78, 95 %CI: 1.75-1.81, P<0.001), unemployed/others ( OR=2.18, 95 %CI: 2.14-2.22, P<0.001), and physical workers ( OR=3.80, 95 %CI: 3.73-3.87, P<0.001). In terms of blood glucose control status, compared with the group that met both control targets, the risk of chronic periodontitis was significantly higher in the group that met only one target ( OR=1.28, 95 %CI: 1.27-1.30, P<0.001) and the group that met neither target ( OR=3.29, 95 %CI: 3.25-3.34) ( P<0.001). The results of ordered Logistic regression showed that after adjusting for all covariates, compared with male patients, female patients had a significantly lower risk of progression to severe periodontitis ( OR=0.77, 95 %CI: 0.76-0.78, P<0.001). In terms of the score of healthy lifestyle, compared with those with a score of 0-2, the risk of progression to severe periodontitis was significantly lower in those with a score of 3 ( OR=0.85, 95 %CI: 0.84-0.86, P<0.001) and 4 ( OR=0.51, 95 %CI: 0.50-0.52, P<0.001). In terms of blood glucose control, compared with the group that met both control targets, the risk of progression to severe periodontitis was significantly higher in the group that met only one target ( OR=1.27, 95 %CI: 1.26-1.29, P<0.001) and the group that meet neither target ( OR=3.24, 95 %CI: 3.21-3.28, P<0.001). Furthermore, poor blood glucose control was significantly positively associated with increased periodontitis severity, demonstrating that worse glycemic control status corresponded to a higher risk of worsening periodontitis severity ( P<0.001). Conclusions:There is an association between the glycemic control status of T2DM patients and chronic periodontitis.
5.Therapeutic early efficacy of finerenone and correlated factors of renal function changes in patients with type 2 diabetes mellitus and chronic kidney disease
Yangmengqi LI ; Guoqin WANG ; Xiaoyi XU ; Fengbo XU ; Nan YE ; Hong CHENG
Chinese Journal of Nephrology 2025;41(10):738-743
Objective:To evaluate effectiveness of finerenone in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the real world, and to analyze the associated factors of renal function progression during treatment.Methods:It was a single-center retrospective study. The patients diagnosed with T2DM and CKD who received finerenone treatment for 3 months in Beijing Anzhen Hospital, Capital Medical University between April 1 and October 1, 2023 were included. The clinical data before and after finerenone treatment were collected. Based on urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), the patients were divided into different groups, and the differences of clinical data before and after treatment were compared respectively. Logistic regression models was used to analyze the correlated factors of renal function changes during the treatment.Results:A total of 151 patients were included with age of 63 (54, 70) years, and 103 males accounted for 68.2%. UACR level after 3 months of finerenone treatment was significantly lower than those before treatment ( Z=-5.051, P<0.001), whereas there was no statistically significant change in eGFR ( P>0.05). Both patients with baseline eGFR ≥60 ml·min -1·(1.73 m 2) -1 ( Z=-4.543, P<0.001) and those with baseline eGFR <60 ml·min -1·(1.73 m 2) -1 ( Z=-2.610, P=0.009) showed significant reductions in UACR after treatment. Both patients with baseline UACR ≥300 mg/g ( Z=-4.681, P<0.001) and those with baseline UACR <300 mg/g ( Z=-1.979, P=0.048) exhibited significantly lower UACR levels after treatment. The percentage reduction in UACR was greater in patients with baseline UACR ≥300 mg/g than in those with baseline UACR <300 mg/g ( Z=-2.102, P=0.036).After 3 months of finerenone therapy, serum potassium level was slightly higher than baseline, but the difference was not statistically significant ( P>0.05).The incidence of hyperkalemia after treatment was higher than baseline in patients with baseline eGFR <60 ml·min -1·(1.73 m 2) -1 ( χ 2=2.558 , P=0.039). During the treatment, 74 patients (49.0%) experienced renal function progression. Multivariate logistic regression analysis identified increased baseline serum albumin <45 g/L was an independent correlated factor of renal function progression during finerenone therapy ( OR=1.934, 95% CI 1.157-3.231, P=0.012). Conclusions:UACR in patients with T2DM and CKD can be reduced significantly after short-term treatment of finerenone. Increased baseline serum albumin level <45 g/L is independently associated with renal function progression during finerenone therapy.
6.The effect of cytomegalovirus and EB virus activation on hematopoietic reconstitution after intensive immunosuppressive therapy for severe aplastic anemia
Qian ZHANG ; Hong WANG ; Xiaoli LI ; Miao MIAO ; Hongxia MA ; Yaoyao SHEN ; Nan WEI ; Kai ZOU ; Wanxiu SU ; Jingqiu YU ; Depei WU ; Limin LIU
Chinese Journal of Internal Medicine 2025;64(6):514-521
Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.
7.Prediction of gamma pass rate for thoracic intensity-modulated radiotherapy plan dose verification using a machine learning model based on planomics
Tiantian CUI ; Xiangyue LIU ; Nan MENG ; Yongqiang WANG ; Hong GE ; Zhaoyang LOU ; Bing LI
Chinese Journal of Radiation Oncology 2025;34(1):81-87
Objective:To construct a machine learning classification prediction model using planning-omics (planomics) features to predict the γ pass rate of intensity-modulated radiotherapy (IMRT) plan dose verification in fixed-field thoracic tumors, and evaluate the application of planomics in radiotherapy quality assurance.Methods:The fixed-field IMRT plans of 240 patients with chest tumors admitted to Department of Radiotherapy, Henan Cancer Hospital from August 2022 to March 2023 were retrospectively analyzed. All plans underwent dose verification using the electronic portal imaging system detector on the Varian accelerator to collect field dose data. The dose verification results were analyzed through Portal Dosimetry in the treatment planning system of Eclipse. The γ pass rate standard was set at 2%/2 mm with a 10% dose threshold. From the planning documents, 48 conventional planning features, 2476 planomics features, and the combination of the previous two feature sets were extracted. Subsequently, an auto-encoder classification model was constructed. To evaluate the classification efficacy of various feature sets, 20 random train-test divisions were conducted by calculating the area under the receiver operating characteristic curve (AUC) values along with the accuracy rates.Results:After the feature selection, 2 conventional features and 16 planomics features were finally selected. In the testing set, the AUC values for the model using combined features, planomics features, and conventional planned features were 0.802±0.030, 0.740±0.069, and 0.673±0.083, respectively. In contrast, in the training set, these AUC values were 0.844±0.074, 0.816±0.047, and 0.687±0.036, respectively. The accuracy rates were 0.752±0.083, 0.703±0.110, and 0.648±0.081 in the testing set, and 0.753±0.098, 0.751±0.075, and 0.624±0.054 in the training set for the combined, planomics, and conventional planning feature sets, respectively.Conclusions:For thoracic fixed-field adjusted radiotherapy planning, the machine learning method based on planomics features can be utilized to build a classification model for predicting the γ pass rate. Combining planomics features with conventional planned features can enhance the predictive performance of the classification models.
8.Clinical study of hysteroscopic combined with laparoscopic repair and reconstruction of diverticulum in the treatment of post-cesarean section uterine diverticulum
Hong WANG ; Jia CHENG ; Zhi-qin HUANG ; Fang NAN
Journal of Regional Anatomy and Operative Surgery 2025;34(6):501-505
Objective To observe the clinical effect of hysteroscopic combined with laparoscopic repair and reconstruction of diverticulum in the treatment of post-cesarean section uterine diverticulum(PCSD).Methods A total of 150 patients with PCSD admitted to the department of gynaecology of our hospital from January 2020 to February 2022 were selected and divided into the transvaginal group(transvaginal repair of diverticulum)and the combined group(hysteroscopic combined with laparoscopic repair and reconstruction of diverticulum)according to different surgical plans,with 75 cases in each group.The general condition of surgery,days of menstrual period,thickness of muscular layer,inflammation-related factor levels,complications and pregnancy in patients with birth plan were recorded in both groups.Results The operation time of patients in the combined group was longer than that in the transvaginal group,and the time of anal exhaustion and postoperative hospital stay of patients in the combined group were shorter than those in the transvaginal group,the differences were statistically significant(P<0.05);There was no significant difference in terms of the intraoperative bleeding volume of patients between the two groups(P>0.05).The high-sensitivity C-reactive protein(hs-CRP),interleukin-4(IL-4),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α)7 days after surgery of patients were lower in both groups compared with those before surgery,and the combined group was lower than the transvaginal group,the differences were statistically significant(P<0.05).Compared with that before the surgery,the days of menstrual period of patietns in both groups 6 and 12 months after the surgery decreased,and the thickness of muscular layer increased,with statistically significant differences(P<0.05);while no statistically significant difference was found in terms of the days of menstrual period or thickness of muscular layer of patients 6 and 12 months after surgery between the two groups(P>0.05).There was no significant difference in the incidence of cumulative complications such as incision infection,hyponatraemia,bladder injury and vaginal infection between the two groups(P>0.05).The intrauterine pregnancy rate of patients with birth plan and the full-term pregnancy rate in the combined group were higher than those in the transvaginal group,the differences were statistically significant(P<0.05).There was no statistically significant difference in the abortion rate or preterm birth rate between the two groups(P>0.05).Conclusion The hysteroscopic combined with laparoscopic repair and reconstruction of diverticulum for patients with PCSD has a fast postoperative recovery,a short hospital stay,and can increase the pregnancy rate of patients with birth plan.
9.Study on the efficacy and safety of Metformin hydrochloride enteric-coated capsules in patients with type 2 diabetes mellitus
Yiming WU ; Jian ZHANG ; Nan GU ; Qijuan DONG ; Ruiyun LIU ; Hong ZHANG ; Haixia LIU ; Yongcai ZHAO ; Lin CHENG ; Lianshan PU ; Fang BIAN ; Gang HE ; Quanmin LI ; Wei DU ; Zhaoling WANG ; Wei XU ; Liyong ZHONG ; Xiaohui GUO
Chinese Journal of Diabetes 2025;33(3):210-214
Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384~0.069)and PPS(-0.139,95%CI-0.390~0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.
10.Underlying target of bullatine A in treating rheumatoid arthritis based on LiP-SMap drug target proteomics
Hao-hong ZHANG ; Nan-ting ZOU ; Chun-fei ZHANG ; Qing-yan MO ; Ming-qian JU ; Xiao-hong LI ; Shuai LIU ; Mao-kui HUANG ; Hong-yun WANG ; Chun-ping WAN
Chinese Pharmacological Bulletin 2025;41(6):1072-1078
Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P<0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P<0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P<0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

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