1.Factors affecting and identification of key environmental determinants of the Oncomelania hupensis snail density in the Yangtze River Delta based on machine learning models
Yinlong LI ; Qin LI ; Suying GUO ; Shizhen LI ; Lijuan ZHANG ; Chunli CAO ; Jing XU
Chinese Journal of Schistosomiasis Control 2026;38(1):14-19
Objective To identify factors affecting and key environmental factors of the Oncomelania hupensis snail density in the Yangtze River Delta region using machine learning methods. Methods Administrative village-level O. hupensis snail survey data in the Yangtze River Delta (including Shanghai Municipality, Jiangsu Province, Zhejiang Province and Anhui Province) from 2011 to 2021 were retrieved from the Information Management System for Parasitic Disease Control of Chinese Center for Disease Control and Prevention. Environmental factor data were captured from the Google Earth Engine platform, including elevation, slope, terrain, normalized difference vegetation index (NDVI), vegetation type, soil type, total petroleum hydrocarbon (TPH), ammonium nitrogen, inorganic nitrogen, dissolved oxygen, pH of water, chemical oxygen demand (COD) and inorganic phosphorus, and climatic factor data in the study region were retrieved from the Copernicus Climate Data Store, including annual precipitation, aridity index and annual mean temperature (AMT). O. hupensis snail survey data in the Yangtze River Delta region from 2011 to 2021 were randomly divided into a training set (70%) and a test set (30%), and five machine learning models were selected for machine learning model construction and comparative analysis of the O. hupensis snail density using the software R 4.3.0, including random forest (RF), eXtreme gradient boosting (XGBoost), support vector machine (SVM), gradient boosting machine (GBM) and neural network (NN). The XGBoost model was employed to construct a predictive model for the O. hupensis snail density, and the impact of each environmental factor on O. hupensis snail distribution was quantified. The SHapley Additive exPlanations (SHAPs) values were calculated to estimate the average contribution of each variable to the model prediction, and the core environmental factors affecting the O. hupensis snail population density were screened. Results Among the five machine learning models, the XGBoost model exhibited the optimal comprehensive performance, with the coefficient of determination (R2) of 0.855, mean squared error (MSE) of 0.188, root mean squared error (RMSE) of 0.434 and mean absolute error (MAE) of 0.155, respectively. Analysis of factors affecting the O. hupensis snail density with the XGBoost model showed that among the 16 environmental factors, the top four high-impact factors ranked by SHAPs values included annual precipitation, elevation, aridity index and NDVI, with cumulative SHAPs contributions of 75%, which was higher than that of other environmental factors. If NDVI was higher than 0.6, the O. hupensis snail density increased with NDVI and peaked if NDVI was 0.8 (1.60 snails/0.1 m2). The O. hupensis snail density increased with elevation if the elevation ranged from 14 to 40 m, and slowly rose if the annual precipitation ranged from 900 to 1 300 mm, and then increased rapidly to the peak (1.52 snails/0.1 m2) if the annual precipitation ranged from 1 300 to 1 500 mm. In addition, the O. hupensis snail density increased rapidly to the maximum (1.60 snails/0.1 m2) if the aridity index ranged from 0.8 to 1.1, and decreased gradually if the aridity index exceeded 1.1. Conclusions The XGBoost model shows excellent performance in prediction of the O. hupensis snail density and identification of key environmental factors in the Yangtze River Delta region. Annual precipitation, elevation, aridity index and NDVI are key environmental factors affecting the distribution and density of O. hupensis snails in the Yangtze River Delta region.
2.Association of mixed exposure to lithium, vanadium, uranium, and bismuth in early pregnancy with gestational weight gain
Jiao LI ; Qi LI ; Shuang CHENG ; Jiayi SONG ; Xiaohui GUO ; Xiang WANG ; Di CHENG ; Kefeng FAN ; Ju WANG
Journal of Environmental and Occupational Medicine 2026;43(4):475-484
Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11+0 to 13+6 weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35+0 to 37+6 weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L−1, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g−1 (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.
3.Exploration of a new model for the construction of medical institution formulation platforms from the perspective of industry-university-research collaborative innovation theory
Kana LIN ; Anle SHEN ; Yejian WANG ; Yanqiong WANG ; Hao LI ; Yanfang GUO ; Youjun WANG ; Xinyan SUN
China Pharmacy 2026;37(2):137-141
OBJECTIVE To explore a model for constructing a platform for medical institution formulation and provide insights for promoting their development. METHODS By systematically reviewing the development status and challenges of medical institution preparations in China, and based on the theory of industry-university-research collaborative innovation, the organizational structure, collaborative processes, and safeguard mechanisms of the platform were designed. RESULTS & CONCLUSIONS Medical institution formulations in China mainly faced challenges such as weak research and development (R&D) capacity, uneven quality standards, and blocked transformation pathways. This study established a full-chain, whole- industry collaborative innovation network covering the government, medical institutions, universities/research institutes, pharmaceutical enterprises, and the market, forming a new “government-industry-university-research-application” five-in-one platform model for medical institution formulations. By establishing mechanisms such as multi-entity collaborative cooperation, full- chain intellectual property management, contribution-based benefit distribution, staged risk-sharing, and third-party evaluation, the model clarified the responsibilities and collaborative pathways of all parties. The new model highlights the whole-process transformation of clinical experience-based prescriptions, enabling precise alignment between clinical needs and technological R&D, as well as between preparation achievements and industrial transformation. While breaking down the barriers of traditional platform construction, it effectively achieves optimal resource allocation and complementary advantages, addresses problems emerging in the development of medical institution preparations, and provides reference value for the formulation of relevant systems.
4.Preliminary application of histological evaluation of donor pancreas biopsy tissue in simultaneous pancreas-kidney transplantation
Jiao WAN ; Hui GUO ; Jiali FANG ; Guanghui LI ; Luhao LIU ; Yunyi XIONG ; Wei YIN ; Tong YANG ; Junjie MA ; Zheng CHEN
Organ Transplantation 2026;17(2):250-256
Objective To preliminarily investigate the safety and efficacy of donor pancreas needle biopsy in simultaneous pancreas-kidney transplantation. Methods Clinical data of 7 cases undergoing donor pancreas biopsy were collected retrospectively. All cases underwent donor pancreas biopsy before or during simultaneous pancreas-kidney transplantation. Frozen section or paraffin sectioning techniques were used for tissue preparation, and hematoxylin-eosin and Masson staining were performed to histologically evaluate the donor pancreas. The quality of donor pancreas was comprehensively assessed by combining histological findings with the donor's clinical data. Postoperative follow-up data of 5 simultaneous pancreas-kidney transplant recipients were collected to summarize the safety of donor pancreas biopsy and the prognosis of transplant recipients. Results The 7 pancreas donors were aged 28 to 62 years, with a body mass index ranging from 20.76 to 27.68 kg/m2. Liver ultrasound indicated fatty liver in 3 cases, while pancreatic ultrasound did not reveal any significant abnormalities. Among them, biopsy was performed on 2 donors after completion of pancreatic procurement and processing, and the frozen section histology showed moderate acute pancreatitis changes (edema of acinar cells, necrosis and inflammatory cell infiltration). Combined with a serum amylase level elevated more than 3 times the upper limit of normal value, these two donor pancreases were finally discarded. The remaining 5 cases underwent biopsy immediately after pancreatic vascular anastomosis during simultaneous pancreas-kidney transplantation, and histological evaluation was performed on paraffin-embedded sections. No biopsy-related complications (such as bleeding, pancreatic fistula, etc.) occurred after transplantation. One recipient died of severe infection 2 months after transplantation, while the other 4 recipients were followed up for more than 5 years, with well-functioning transplant kidneys and pancreases. Conclusions Donor pancreas biopsy is relatively safe, and the risk of biopsy-related complications after transplantation is controllable. Comprehensive assessment of donor pancreas quality by combining histological evaluation with the donor's clinical indicators is conducive to improving the accuracy of donor pancreas selection and organ utilization.
5.Analyses of infection characteristics of human respiratory syncytial virus in hospitalized children at a pediatric hospital in Shanghai from 2021 to 2024
Jing WANG ; Weiqin JIANG ; Yuzhe GUO ; Lijiao LIU ; Jian LIU
Shanghai Journal of Preventive Medicine 2026;38(2):97-103
ObjectiveTo analyze the infection characteristics of human respiratory syncytial virus (HRSV) among children hospitalized with acute lower respiratory tract infection (ALRTI) in a specialized pediatric hospital in Shanghai, so as to provide evidence-based support for optimizing the prevention and control strategies and clinical diagnosis and treatment of respiratory tract infections in children in this region. MethodsA retrospective analysis was performed to the clinical and etiological data of 29 260 children hospitalized for ALRTI in Shanghai Children’s Hospital from January 2021 to December 2024. HRSV and 12 other common respiratory pathogens were detected with multiplex polymerase chain reaction (PCR) and capillary electrophoresis. Demographic and clinical data were collected for statistical analyses. A total of2 412 cases with positive HRSV were divided into the severe group and the non-severe group. Clinical characteristics between the two groups were compared using the Mann-Whitney U test and the chi- square (χ2) test. Additionally, the related influencing factors of severe HRSV infection were explored. ResultsThe overall positivity rate of HRSV from 2021 to 2024 was 8.24% (2 412/29 260), with statistically significant differences observed across the four years (χ2=389.42, P<0.001). The highest positivity rate was in 2021 (14.76%), with a high prevalence throughout the year. In 2022, when non-pharmaceutical interventions (NPIs) were implemented, the HRSV positivity rate was the lowest (4.93%), with a winter-dominant epidemic pattern. In 2023, after the NPIs were lifted, the HRSV positivity rate showed a slight rebound (8.14%), presenting a double-peak pattern. In 2024, the HRSV positivity rate slightly decreased compared to that in 2023 (6.29%), exhibiting a winter and spring-dominant epidemic pattern. Among the hospitalized children with ALRTI, the HRSV positivity rate in males (8.85%) was higher than that in females (7.51%), and the difference was statistically significant (χ2=17.33, P<0.001). Age distribution showed that 82.26% (1 984/2 412) of HRSV infections occurred in children aged 3 years old and below. Besides, as age increased, the infection rate of HRSV showed a gradually decreasing trend (P<0.001). Among the 2 412 children with HRSV infection, the proportion of severe cases was 22.31% (538/2 412), while the non-severe cases accounted for 77.69% (1 874/2 412). Compared with non-severe cases, severe cases were more frequently presented with high fever, longer duration of wheezing, as well as higher rates of underlying diseases or co-infection with Mycoplasma pneumoniae (P<0.001). ConclusionThe prevalence intensity of HRSV varied yearly from 2021 to 2024. After the removal of NPIs in 2023, a slight rebound with a double-peak epidemic pattern was observed. HRSV remained a common pathogen in children hospitalized for ARLTI, and children aged 3 years old and below constituted the highest proportion for infection. Compared with non-severe cases, those with severe HRSV infections were more prone to presenting with high fever and a longer duration of wheezing. Children with positive HRSV who had underlying diseases or co-infection with Mycoplasma pneumonia were more likely to develop severe conditions.
6.Construction and application of anti-tumor drug prescription review decision-support system in a large general hospital
Jing ZANG ; Run GAN ; Qi YANG ; Yan CHEN ; Cheng GUO ; Jianping ZHANG ; Fengqian LI ; Quanjun YANG
China Pharmacy 2026;37(6):794-799
OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources, including national and local pharmaceutical administration policies, clinical practice guidelines/consensus, hospital information systems data, and genetic testing results, were integrated. Adhering to the principles of structure, standardization and dynamic updating, a knowledge base covering chemotherapeutic, targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed, and a closed-loop prescription review system was successfully established, encompassing pre-prescription real-time intervention, in-process interactive review, and post-prescription evaluation and analysis. From 2021 to 2024, the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions, 22 577 alerts were generated, with Cisplatin for injection (lyophilized) being the most frequently alerted drug (13 445 alerts), and “ototoxicity risk due to combined use” alerts remained high (7 682 alerts). For methotrexate-containing prescriptions, 3 721 alerts were recorded, primarily related to “precaution-related issues” (76.4%, 2 843/3 721). For doxorubicin-containing prescriptions, 17 301 alerts were triggered, primarily related to “dosage and administration” (14 315 alerts). For human epidermal growth factor receptor 2-targeted agents-containing prescriptions, 1 007 alerts were issued, mostly related to “reimbursement restrictions” (956 alerts). For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions, the alerts increased year by year, totaling 13 273 alerts, primarily related to “inappropriate indication” (9 118 alerts). Over the 4 years, the physician response rates to system alerts were 21.4%, 27.1%, 33.5% and 51.6%, respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review, encompassing a closed-loop process of “real-time pre-event intervention, interactive in-event prescription review, post-event evaluation and analysis”, has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital, where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally, the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.
7.Influencing factors of bladder management practices in patients with spinal cord injury
Zhirong LUO ; Xuyan GUO ; Qi XUE ; Xiao TAN ; Yunhua JI ; Fuxun ZHANG ; Yong JIAO ; Bo ZHANG
Journal of Modern Urology 2025;30(4):284-289
Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury,so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge,there were 9 cases of self-catheterization,19 cases of intermittent catheterization,22 cases of reflexive voiding,26 cases of long-term catheterization,and 2 cases using urinary collector.At the end of follow-up,there were 15 cases of self-catheterization,8 cases of intermittent catheterization,34 cases of reflexive voiding,14 cases of long-term catheterization,and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ
=21.43,P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.
8.Analysis of the causal relationship between gut microbiota and bladder cancer with Mendelian randomization
Xuyan GUO ; Zhirong LUO ; Qi XUE ; Yunhua JI ; Xiao TAN ; Yong JIAO
Journal of Modern Urology 2025;30(5):400-407
Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer,but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW),MR-Egger,weighted median,maximum likelihood,robust adjustment feature score and MR-PRESSO,with IVW as the primary analysis method.Additionally,sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR:1.42),Desulfovibrionales (Order) (OR:1.48),Eubacterium ruminantium group (OR:1.33),Olsenella (OR:1.24),Ruminococcaceae UCG002 (OR:1.39),Ruminococcaceae UCG005 (OR:1.42) and Ruminococcaceae UCG013 (OR:1.64) significantly increased the risk of bladder cancer.Conversely,Bacteroidetes (Phylum) (OR:0.61),Eubacterium brachy group (OR:0.80),Ruminococcaceae UCG004 (OR:0.73),Rikenellaceae (Family) (OR:0.67),Lachnospiraceae ND3007 group (OR:0.47), Adlercreutzia (OR:0.73) and an unknow genus (OR:0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer,among which Lachnospiraceae UCG004,Desulfovibrionales (Order),Eubacterium ruminantium group,Olsenella,Ruminococcaceae UCG002,Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer,while Bacteroidetes (Phylum),Eubacterium brachy group,Ruminococcaceae UCG004,Rikenellaceae (Family),Lachnospiraceae ND3007 group,Adlercreutzia and an unknown genus are the protective factors.
9.Shenxiao Tongluo Prescription Alleviates Kidney Injury in Diabetic Rats via PGC-1α/SIRT3/HIF-1α Pathway
Cangcang XU ; Xianbing GUO ; Guang LI ; Wenhao JIAO ; Yang ZHAO ; Yingjun DING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):108-116
ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy (DN) by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/sirtuin-3 (SIRT3)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway. MethodsSixty-five SD rats were randomized into a sham group (10 rats) and a modeling group (55 rats), and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin (35 mg·kg-1) to prepare a DN model. After successful modeling, the rats were randomized into model, empagliflozin (10 mg·kg-1), and low-, medium-, and high-dose (7.656, 15.312, 30.624 g·kg-1, respectively) Shenxiao Tongluo prescription groups. The urine microalbumin (UmAlb), blood urea nitrogen (BUN), and serum creatinine (SCr) levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate, superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissue. Hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 (DRP1) and pyruvate kinase M2 (PKM2) in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α, SIRT3, HIF-1α, dynamin-related protein 1 (Drp1), optic atrophy 1 (OPA1), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2) in the kidney tissue. ResultsCompared with the sham group, the model group showed elevated levels of UmAlb, BUN, SCr, lactate, and MDA, decreased SOD level (P<0.05), glomerular hypertrophy, thickening of the mesangial basement membrane, vacuolar degeneration of renal tubular epithelial cells, and infiltration of renal interstitial inflammatory cells, oval mitochondria with disordered, blurred or disappearing cristae, down-regulated protein levels of PGC-1α, SIRT3, and OPA1, and up-regulated protein levels of HIF-1α, DRP1, HK2, and PKM2 (P<0.05). Compared with the model group, the treatment in all the groups increased the body weight, lowered the levels of GLU, UmAlb, BUN, and MDA, raised the level of SOD, alleviated the pathological damage in the kidney tissue and mitochondrial damage, up-regulated the expression of PGC-1α, SIRT3, and OPA1, and down-regulated the expression of HIF-1α, DRP1, and PKM2 (P<0.05). Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 (P<0.05), which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway, thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.
10.Shenxiao Tongluo Prescription Alleviates Kidney Injury in Diabetic Rats via PGC-1α/SIRT3/HIF-1α Pathway
Cangcang XU ; Xianbing GUO ; Guang LI ; Wenhao JIAO ; Yang ZHAO ; Yingjun DING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):108-116
ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy (DN) by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/sirtuin-3 (SIRT3)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway. MethodsSixty-five SD rats were randomized into a sham group (10 rats) and a modeling group (55 rats), and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin (35 mg·kg-1) to prepare a DN model. After successful modeling, the rats were randomized into model, empagliflozin (10 mg·kg-1), and low-, medium-, and high-dose (7.656, 15.312, 30.624 g·kg-1, respectively) Shenxiao Tongluo prescription groups. The urine microalbumin (UmAlb), blood urea nitrogen (BUN), and serum creatinine (SCr) levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate, superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissue. Hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 (DRP1) and pyruvate kinase M2 (PKM2) in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α, SIRT3, HIF-1α, dynamin-related protein 1 (Drp1), optic atrophy 1 (OPA1), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2) in the kidney tissue. ResultsCompared with the sham group, the model group showed elevated levels of UmAlb, BUN, SCr, lactate, and MDA, decreased SOD level (P<0.05), glomerular hypertrophy, thickening of the mesangial basement membrane, vacuolar degeneration of renal tubular epithelial cells, and infiltration of renal interstitial inflammatory cells, oval mitochondria with disordered, blurred or disappearing cristae, down-regulated protein levels of PGC-1α, SIRT3, and OPA1, and up-regulated protein levels of HIF-1α, DRP1, HK2, and PKM2 (P<0.05). Compared with the model group, the treatment in all the groups increased the body weight, lowered the levels of GLU, UmAlb, BUN, and MDA, raised the level of SOD, alleviated the pathological damage in the kidney tissue and mitochondrial damage, up-regulated the expression of PGC-1α, SIRT3, and OPA1, and down-regulated the expression of HIF-1α, DRP1, and PKM2 (P<0.05). Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 (P<0.05), which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway, thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

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