Background:Traditional Chinese medicine (TCM) formulations are increasingly used in combination with mesalazine to treat mild-to-moderate active ulcerative colitis (UC). However, direct comparisons between various TCM regimens are limited. Methods:We performed a frequentist network meta-analysis of 34 randomized controlled trials (n = 2,854) comparing oral mesalazine (1.0-4.0 g/day) alone versus mesalazine plus one of eight TCM formulations: Kangfuxin solution, Shaoyao decoction, Glycyrrhizae decoction, Scutellaria decoction (Huangqin granules), Baitouweng decoction (Pulsatilla; retention enema), Shenling Baizhu Powder, CurQD formula, or Fufangkushen capsules. Outcomes included clinical efficacy, adverse events, Mayo score, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and intestinal Bifidobacteria, Lactobacilli, and Escherichia coli. Risk ratios (RRs) were calculated for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Treatments were ranked using surface under the cumulative ranking curve (SUCRA). Results:Most TCM-mesalazine combinations improved clinical efficacy versus mesalazine alone. CurQD and Kangfuxin had the highest probabilities of being most effective for symptom improvement (SUCRA 96.7% and 72.7%, respectively); the direct CurQD-mesalazine comparison showed RR = 2.67 (95% CI 1.16-6.14). Adverse-event rates were similar across regimens, with lower incidence of adverse events. Mayo score reductions were greatest with Glycyrrhizae decoction (MD = -1.40), Baitouweng decoction via retention enema (MD = -1.09), and Kangfuxin solution (MD = -1.07). Scutellaria granules produced the largest IL-6 decrease (MD = -53.28 pg/mL) and ranked highest for TNF-α reduction, followed by Kangfuxin. For gut microbiota, Shaoyao decoction ranked highest for increasing Bifidobacteria, Glycyrrhizae decoction for increasing Lactobacilli, and Glycyrrhizae also reduced E. coli (MD = -1.93). Conclusion:Combining mesalazine with selected TCM formulations can enhance clinical response, reduce inflammatory cytokines, and beneficially modulate gut microbiota without increasing adverse events. CurQD or Kangfuxin may be prioritized for symptomatic improvement, Glycyrrhizae or Baitouweng for Mayo score reduction, Scutellaria for cytokine control, and Shaoyao or Glycyrrhizae for microbiota modulation. High-quality multicenter RCTs are warranted to confirm these comparative rankings.

Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tubules. However, the role of its active form, ChREBP-β, was previously unclear. In this study, ChREBP-β overexpression and ChREBP knockout mouse models were utilized to investigate the effects of excessive fructose intake in vivo. In addition, primary renal tubular epithelial cells from mice and human kidney-2 (HK2) cells were applied for further validation in vitro. We found that ChREBP-β leads to increased transcription to mediate endoplasmic reticulum stress and mitochondrial dysfunction, which ultimately impairs renal function. Our findings underscore the critical role of ChREBP-β in fructose-related renal disorders.

We aimed to describe the rationale, design, and overall baseline characteristics of the trial evaluating the efficacy, safety, and tolerability of survodutide in Chinese adults with overweight or obesity (SYNCHRONIZE™-CN, NCT06214741). In this 76-week, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, Chinese participants were randomized 1:1:1 to once-weekly subcutaneous survodutide (3.6 mg or 4.8 mg) or placebo plus lifestyle intervention. Participants with either body mass index (BMI) ≥ 28 kg/m2 or BMI ≥ 24 kg/m2 and at least one obesity-related complication were eligible. The primary endpoints were the percentage change in body weight and achievement of body weight reduction ≥ 5

Diabetes is a growing public health burden across the Asia-Pacific (APAC) region. The increasing use of continuous glucose monitoring (CGM) holds significant potential to improve glycemic control and safety outcomes in individuals with diabetes. However, CGM devices in APAC vary widely in technical performance, clinical validation, and regulatory oversight, posing risks of inaccurate readings and treatment errors, especially for nonadjunctive integrated CGM (iCGM) systems. This review synthesizes the literature and regional insights on CGM regulatory frameworks, accuracy standards, and unmet needs. The authors highlight the U.S. Food and Drug Administration (FDA) iCGM standards as the most stringent global standards. Adopting FDA iCGM criteria alongside the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reporting recommendations, with contextual modifications for diverse epidemiological, infrastructural, and socioeconomic settings in APAC, is explored. A phased, regionally coordinated approach is proposed, incorporating voluntary benchmarks, capacity-building for lower-resourced regulators, regulatory reliance mechanisms, and shared postmarketing surveillance platforms. Emphasis is placed on multistakeholder collaboration and region-specific validation studies. Harmonizing iCGM regulatory standards in APAC is anticipated to enhance device accuracy, safety, and interoperability, improve diabetes care, and streamline regulatory processes, serving as a model for regulatory excellence for other emerging medical technologies.

Diabetic retinopathy remains a major cause of vision loss, and therapeutic strategies beyond anti-vascular endothelial growth factor treatment are still needed. This study aimed to identify genetically supported druggable targets for diabetic retinopathy and to evaluate finerenone as a candidate therapeutic intervention in experimental retinopathy. We performed druggable Mendelian randomization by integrating druggable-gene resources, blood cis-expression quantitative trait locus data, and a large genome-wide association dataset for diabetic retinopathy. Significant genes were further evaluated using colocalization analysis, functional enrichment, protein–protein interaction network analysis, drug prediction, and molecular docking. Finerenone was subsequently assessed in db/db mice and in the oxygen-induced retinopathy model. Thirty candidate druggable genes were associated with diabetic retinopathy after false discovery rate correction. Among them, CDH2 was the only candidate showing significant colocalization with diabetic retinopathy risk, with a posterior probability for a shared causal variant of 0.85. Protein–protein interaction analysis showed relatively high connectivity of CDH2 within the candidate network, and molecular docking suggested a favorable predicted interaction between finerenone and N-cadherin. In vivo, finerenone reduced avascular and neovascular areas in oxygen-induced retinopathy retinas and decreased retinal expression of TNF-α, IL-1β, and N-cadherin in db/db mice. These findings prioritize CDH2/N-cadherin as a genetically supported candidate target in diabetic retinopathy and support finerenone as a potential therapeutic candidate. The retinal protective effects of finerenone may be associated with suppression of inflammatory responses and downregulation of N-cadherin, although the direct mechanistic link requires further validation.

AIMS:To evaluate the glycaemic outcomes and safety of insulin glargine 300 U/mL (Gla-300) in Chinese people with uncontrolled type 2 diabetes (T2D) by baseline age and disease duration. MATERIALS AND METHODS:INITIATION was a 24-week, interventional, single-arm study where adults with T2D (glycated haemoglobin [HbA1c] 7.5%-11.0%) received Gla-300. This post-hoc subgroup analysis assessed HbA1c change from baseline to week 24 (primary endpoint), other glycaemic endpoints, insulin dose, hypoglycaemia, body weight change, and treatment satisfaction (using the Diabetes Treatment Satisfaction Questionnaire [DTSQ]) by baseline age (<60 or ≥ 60 years) and disease duration (<5, ≥5 to <10 or ≥10 years in insulin-naïve participants, and <10, 10 to <15 or ≥15 years in those with prior basal insulin [BI]). RESULTS:Of 568 participants, 191 were insulin-naïve and 377 had received prior BI. Over 24 weeks, Gla-300 improved HbA1c in all age and disease duration subgroups. The least squares mean HbA1c change ranged from -1.02% (-11.1 mmol/mol) to -1.55% (-16.9 mmol/mol) in insulin-naïve participants and from -0.55% (-6.0 mmol/mol) to -0.76% (-8.3 mmol/mol) in prior BI participants. HbA1c <7.0% (<53 mmol/mol) achievement (ranging from 19.5% to 40.7%), other glycaemic endpoints, insulin dose increases, body weight changes and DTSQ score improvements did not significantly differ across the majority of subgroups, and the hypoglycaemia risk remained low. CONCLUSIONS:Gla-300 improved glycaemic control with a low risk of hypoglycaemia in Chinese people with T2D across all ages and disease durations, including older individuals and those with long-standing diabetes.

BACKGROUND:Insulin GZR4 (GZR4) is a once-weekly insulin currently under development. This phase 2 trial assessed the efficacy and safety of once-weekly (QW) GZR4 versus once-daily (QD) insulin degludec (IDeg) in Chinese people with type 2 diabetes (T2D). METHODS:This 16-week, randomized, open-label, multicenter, treat-to-target phase 2 trial consisted of 2 cohorts: Cohort A enrolled insulin-naïve people; Cohort B enrolled people previously treated with basal insulin. Participants were randomly assigned (1:1) to receive GZR4 or IDeg. The primary outcome was the change in HbA1c from baseline to week 16. RESULTS:Between August 22, and September 22, 2023, 179 participants were enrolled and allocated to Cohort A (n = 83) and Cohort B (n = 96). The estimated mean change in HbA1c from baseline to week 16 was -1.50 percentage points in the GZR4 group vs -1.48 percentage points in the IDeg group in Cohort A (estimated treatment difference [ETD] of -0.02 percentage points [95% CI -0.34 to 0.30], p = 0.902), -1.26 percentage points in the GZR4 group vs -0.87 percentage points in the IDeg group in Cohort B (ETD -0.38 percentage points [95% CI -0.66 to -0.11], p = 0.007). At week 16, GZR4 and IDeg group showed a similar proportion of participants achieving HbA1c targets. The treatment-emergent adverse events did not differ between two groups. The incidence of hypoglycemia (mostly level 1) was slightly higher in participants receiving GZR4 than IDeg, particularly in Cohort B. No severe hypoglycemia (level 3) was reported. CONCLUSIONS:In this phase 2 trial, once-weekly GZR4 demonstrated effective glycemic control over 16 weeks in both insulin-naïve patients and those previously treated with basal insulin. The incidence of hypoglycemia was slightly higher with GZR4, particularly in the basal insulin-treated group, though no severe hypoglycemic events were reported. These findings warrant further investigation in larger phase 3 trials, which will utilize an adjusted, more precise molar-dose potency of GZR4 to fully characterize its benefit-risk profile.

Background:Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease despite advances in glucose-, blood pressure-, and albuminuria-lowering therapies. The glucose-responsive transcription factor carbohydrate response element-binding protein (ChREBP; encoded by MLXIPL) regulates glycolytic-lipogenic programs, yet its causal contribution to renal injury is challenging to disentangle in advanced DKD, where bulk kidney transcriptomes reflect tissue remodeling and cellular compositional shifts. Methods:We integrated two-sample Mendelian randomization (MR), kidney transcriptomic stratification, network analyses, and experimental validation. MR used blood cis-eQTL instruments for MLXIPL to estimate causal effects on type 2 diabetes (T2D) and urinary albumin-to-creatinine ratio (UACR), including a non-diabetic UACR stratum. In kidney transcriptomics (GSE30529), we evaluated remodeling-related confounding and applied within-DKD, median-based MLXIPL-high/low stratification for GSEA/GSVA and functional/network inference. Key observations were validated in db/db mice and primary proximal tubular epithelial cells (PTECs) exposed to high glucose with matched osmotic control. Results:Genetically predicted higher MLXIPL expression was associated with increased T2D risk across multiple phenotype definitions and with higher UACR, including replication in non-diabetic individuals. Within DKD, MLXIPL heterogeneity tracked metabolic programs by GSEA and divergent pathway activity by GSVA, while signatures related to profibrotic and proliferative remodeling were concomitantly enriched in the low-MLXIPL subgroup. Network analyses positioned MLXIPL/ChREBP within a dense metabolic interaction and regulatory landscape. Experimentally, ChREBP and Mlxipl were increased in db/db kidneys and induced by high glucose in PTECs, accompanied by coordinated upregulation of lipogenic targets (Acly, Acaca, Fasn, Srebf1) and an inverse relationship with Ppargc1b. Conclusions:Integrating genetic inference, confounding-aware kidney transcriptomics, network biology, and experimental validation, our study supports MLXIPL/ChREBP as a pathogenic nutrient-sensing node linking diabetes susceptibility to renal injury and maladaptive metabolic remodeling in DKD, providing a mechanistic rationale for targeting this axis to mitigate residual renal risk.

Introduction and Objective: Finerenone was approved in China in 2022 for adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). This study aimed to describe the characteristics and clinical outcomes in patients with CKD and T2D using finerenone in a real-world setting in China. Methods: A retrospective study was conducted using electronic health records data in Tianjin, China. Adult patients with CKD and T2D who initiated finerenone between 1 JAN 2023 and 31 DEC 2024 were included, with up to 28.8 months of follow-up. Patient characteristics were descriptively summarized. Relative change from baseline in urine albumin-to-creatinine ratio (UACR) was evaluated at 4 months. Hyperkalemia occurrence was assessed. Results: The study included 6,537 patients. Baseline characteristics are provided in Table 1. At baseline, in 2,561 patients with UACR and estimated glomerular filtration rate (eGFR) values, 43.5% and 41.4% were categorized as moderate and high KDIGO risk categories. UACR was reduced by 40.7% (95% confidence interval: 32.2%, 49.1%) at 4 months. The incidence rate of hyperkalemia was 4.1 per 100 person-years. Conclusion: This study provides evidence on characteristics and clinical outcomes of finerenone new users based on real-world data in China. Patients who initiated finerenone experienced a significant reduction in UACR, with a low risk profile for hyperkalemia. Disclosure B. Sun: None. C. Shan: None. Y. Kong: None. Z. Xu: Other - Employee of Bayer Healthcare Company Ltd; Current; Bayer AG. H. Yang: Other - employee for Bayer Healthcare Company LTD.; Current; Bayer AG. N.G. Oberprieler: Employee; Current; Bayer AG. H. Wei: None. L. Chen: Research Support; Current; AstraZeneca, Lilly, Gan & Lee Pharmaceuticals, Novo Nordisk, Sanofi. Funding This study was initiated by Bayer Healthcare Company Ltd. and funded by Bayer AG.

The global incidence of metabolic disorders has shown a significant upward trend, with growing evidence suggesting a strong association between their development and maternal environmental factors during gestation, including dietary patterns. This study investigated the effects of maternal fructose consumption during pregnancy on hepatic glucose metabolism in male mouse offspring. The results revealed that downregulation of glucokinase expression was closely associated with impaired glucose metabolism in the liver tissue of the offspring. Furthermore, DNA Methyltransferase 3 beta (DNMT3B)-mediated hypermethylation of the glucokinase (GCK, protein: GK) promoter region was responsible for this transcriptional repression. This study established that maternal fructose intake during pregnancy led to reduced GK expression through DNMT3B-dependent epigenetic modifications, resulting in abnormal glucose metabolism. Importantly, pharmacological intervention with a GK activator effectively ameliorated these metabolic abnormalities. Besides, the expression of DNMT3B was regulated by CCAAT Enhancer Binding Protein Beta (C/EBPβ) at the transcriptional level. In brief, this study demonstrated that maternal fructose intake has a negative effect on glucose metabolism in the liver of offspring and highlights the importance of dietary guidance during pregnancy and diabetes prevention.

Guideline on Treatment Intensification with Injectable Therapies Beyond GLP-1 RA Monotherapy in Type 2 Diabetes. Aims To provide evidence-based recommendations for selecting injectable therapies in adults with type 2 diabetes (T2DM) who have suboptimal response to GLP‑1 receptor agonists (GLP‑1 RAs). Methods Using the GRADE framework, a systematic search (updated November 2025) identified eight RCTs evaluating four intensification strategies (switching to another GLP‑1 RA, switching to dual GIP/GLP‑1 RA, switching to fixed‑ratio combination (FRC), or adding basal insulin). A 22‑member Guideline Development Group from 11 Asia‑Pacific countries formulated recommendations requiring ≥ 80% consensus. AGREE and RIGHT checklists guided reporting. Results The panel conditionally recommends against switching to another GLP‑1 RA (very low certainty). It conditionally recommends switching to dual GIP/GLP‑1 RA (low certainty) for glycemic and weight benefits, switching to FRC (very low to moderate certainty) when prioritizing glycemic improvement, and adding basal insulin (low certainty) with structured education. Choice among strategies should be individualized. Conclusions This guideline offers a framework for treatment intensification beyond GLP‑1 RA monotherapy in T2DM, emphasizing shared decision‑making based on glycemic goals, hypoglycemia risk, weight needs, and patient preferences.

Lipohypertrophy, characterized by subcutaneous adipose tissue accumulation at sites of insulin administration, affects 29-76% of insulin-treated people with diabetes (PwD), yet remains underrecognized. This complication significantly impacts glycemic control through unpredictable insulin absorption, necessitating up to 25% higher insulin doses and increasing care costs. An evidence-informed consensus initiative was warranted to establish recommendations for the screening, prevention, and management of lipohypertrophy. A modified Delphi methodology was employed involving 13 international experts in endocrinology, primary care, and diabetes research. A structured literature review informed five consensus rounds, leading to fifteen statements addressing epidemiology, risk factors, clinical presentation, diagnosis, prevention, management, and education/training/systems. Inadequate injection site rotation was identified as the strongest modifiable risk factor for lipohypertrophy. The panel recommends systematic injection site examination every 6 months during the first 2 years of insulin therapy, then annually, with more frequent screening for high-risk PwD. Standardized examination protocols incorporating visual inspection and systematic palpation were endorsed, with ultrasound reserved for detecting subclinical lipohypertrophy. Prevention strategies emphasize proper education, site rotation, and single-use needle practices. Implementation of consensus recommendations presented here may improve glycemic outcomes, reduce insulin requirements and cost of care, and enhance quality of life for PwD on insulin therapy.

Introduction and Objective: Combined glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are increasingly prescribed in China. This post hoc analysis of SCHOLAR (NCT06351748) investigated A1C changes and the safety profile of combined semaglutide (sema)-SGLT2i. Methods: Adults with type 2 diabetes (T2D) in the Tianjin electronic health record database with ≥1 SGLT2i prescription within 6 months of initiating once-weekly subcutaneous sema were included. Participants were grouped according to sema prescription (continuous or not) and by baseline (BL) A1C. Key endpoints: participants prescribed sema-SGLT2i (%); A1C change (BL to month 6); sema-SGLT2i safety profile. Results: In total, 11,361 participants (42.3% of SCHOLAR full analysis set) were prescribed sema-SGLT2i, 3607 (31.7%) of whom were prescribed continuous sema. Overall, mean (SD) BL values: age 57.2 (12.4) yrs; T2D duration 4.6 (3.2) yrs; BMI 26.5 (3.9) kg/m2; A1C 8.04% (1.74). Sema-SGLT2i was associated with a significant A1C reduction (p<0.0001); continuous sema use and BL A1C ≥7% groups had the greatest reduction vs other groups (Figure A). There were no new safety concerns with combination therapy (Figure B). Conclusion: Combined sema-SGLT2i was associated with A1C reductions, with greater reductions in continuous vs non-continuous sema groups, and no new safety concerns. Disclosure S. Wang: None. B. Dong: Employee; Current; Novo Nordisk. Z. Shen: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. L. Chen: Research Support; Current; AstraZeneca, Lilly, Gan & Lee Pharmaceuticals, Novo Nordisk, Sanofi.

Traditional Chinese medicine (TCM) has increasingly attracted the attention of researchers as a potential complementary or supportive approach for selected rare diseases, but the characteristics and evidentiary strength of this literature remain unclear. This Correspondence summarizes publication patterns identified for the 121 conditions in the First Chinese Rare Disease List using Chinese and English sources searched from database inception through June 30, 2021. Fifty-five rare diseases were identified in 3,030 TCM-related publications, though the ten most frequently studied conditions accounted for more than 80% of the literature. Generalized myasthenia gravis, idiopathic pulmonary fibrosis, and multiple sclerosis together accounted for nearly half of all publications. Clinical studies and case reports or experience summaries predominated, whereas experimental studies represented only 9.03%. Oral herbal formulas were the most frequently reported intervention, and more than 95% of publications originated from mainland China. These patterns indicate growing interest but a fragmented, geographically concentrated, and methodologically limited evidence base; publication volume should not be interpreted as evidence of efficacy or safety. Future research should prioritize mechanistic studies, standardized and innovative clinical designs, rigorous safety and quality-control procedures, real-world evidence, patient-centered outcomes, and international collaboration to clarify the potential roles and limitations of TCM in rare disease management.

BACKGROUND:Diabetes-associated cognitive decline (DACD) is gradually gaining attention as a major complication of diabetes. However, to date, the specific molecular mechanisms underlying DACD have not been thoroughly characterized. METHODS:Db/db and streptozotocin (STZ) treated high-fat diet (HFD)-induced mice were established. Different behavioural assessments were performed, followed by evaluation of mitochondrial homeostasis, including mitochondrial morphology and function. Mitochondrial dynamics proteins, synaptic-related proteins and O-GlcNAc cycling enzymes were examined. Thereafter, OGT-interacting proteins were identified using co-immunoprecipitation mass spectrometry. Additionally, mouse hippocampal neuronal cells were treated with OGT siRNA and subsequent changes were measured. Mice were stereotaxically injected with adeno-associated viruses to overexpress OGT specifically in the hippocampus, and relevant in vivo experiments were performed. Finally, mice received semaglutide for 16 weeks and subsequent changes were assessed. RESULTS:Decreased OGT expression disrupted mitochondrial homeostasis and led to neuronal injury and cognitive impairment in diabetic mice. In addition, hippocampus-specific OGT overexpression improved DACD. Mechanistically, OGT deficiency resulted in a reduced mitochondrial membrane potential, promoting mitochondrial fission and impairing mitochondrial function by modulating DRP1 function. Furthermore, our results showed that semaglutide alleviated DACD through the OGT/DRP1 pathway. CONCLUSIONS:OGT deficiency-mediated mitochondrial homeostasis imbalance contributes to the occurrence of DACD, and semaglutide with an OGT protective effect may be a potential therapeutic approach for DACD.

The aim of this study was to evaluate changes in clinical parameters among adults with type 2 diabetes (T2D) after initiating subcutaneous semaglutide in Chinese clinical practice. SCHOLAR was a retrospective cohort study using data from the Tianjin regional electronic health records database, including adults with T2D who initiated once-weekly semaglutide (full analysis set [FAS]). Endpoints included change in glycated hemoglobin (HbA1c) and proportion with HbA1c < 7.0

BackgroundEarly risk stratification for gestational dysglycemia is important for improving maternal and neonatal outcomes. Derived from fasting triglycerides and glucose, the triglyceride–glucose (TyG) index is widely used to approximate insulin resistance, whereas the cholesterol-high-density lipoprotein-glucose (CHG) index incorporates broader lipid metabolism. We compared the associations and discriminative performance of TyG and CHG in a national survey discovery cohort and an independent clinical validation cohort.MethodsWe analyzed a survey-weighted discovery cohort from NHANES 2007–2018, in which the primary outcome was self-reported GDM history. We further evaluated an independent validation cohort with clinically diagnosed GDM (n = 217). Associations and predictive performance were assessed using multivariable logistic regression, receiver operating characteristic (ROC) analysis, calibration analysis, and decision curve analysis (DCA). Additional analyses included adjustment for continuous fasting blood glucose in NHANES, supportive analyses restricted to currently pregnant NHANES participants from 2007–2012 using proxy-defined gestational fasting dysglycemia (fasting blood glucose ≥5.1 mmol/L), and gestational-week-adjusted sensitivity analyses in the validation cohort.ResultsIn the NHANES discovery cohort, CHG showed a stronger association with self-reported GDM history than TyG in the primary adjusted models and yielded a numerically higher AUC than TyG. After additional adjustment for continuous fasting blood glucose, the association for TyG was attenuated, whereas CHG remained significantly associated. In the clinical validation cohort, CHG also showed numerically higher discriminative performance than TyG, and the overall findings remained directionally consistent after gestational-week adjustment. Supportive analyses in currently pregnant NHANES participants showed directionally similar but statistically imprecise estimates because of the limited sample size.ConclusionBoth TyG and CHG are simple, low-cost indices associated with gestational dysglycemia/GDM. Across the discovery and validation cohorts, CHG generally showed stronger associations and numerically better discrimination than TyG; however, its overall discriminative performance remained modest and should be interpreted as that of a potential risk marker rather than a standalone clinical screening tool. Further prospective studies are needed to validate these findings.

Background:As a progressive and fatal interstitial lung disease, the treatment options for idiopathic pulmonary fibrosis (IPF) are currently limited. Tripterygium wilfordii polysaccharide tablets (TWGT) have shown potential in anti-fibrosis, but their specific mechanism in pulmonary fibrosis is still unclear. This research aimed to evaluate the therapeutic potential of TWGT in bleomycin-caused pulmonary fibrosis, as well as to delineate its related molecular pathways. Methods:A rat IPF model was built via intratracheal instillation of bleomycin (5 mg/kg), and rats were divided into sham, IPF, IPF + TWGT (6 mg/kg), IPF + prednisolone acetate (PA) (3 mg/kg), and IPF + TWGT + PA groups. Lung tissues were collected at 7, 14, and 28 days post-modeling for histopathological evaluation, transcriptome sequencing, and immunofluorescence staining. Serum levels of cytokines were measured by enzyme-linked immunosorbent assay (ELISA), and Th17 cell proportions were analyzed by flow cytometry. Results:Histopathological results showed that TWGT significantly alleviated alveolar structural damage, inflammatory cell infiltration, and collagen deposition at 7, 14, and 28 days post-modeling. Transcriptome analysis identified 364 and 2,271 differentially expressed genes (DEGs) in IPF vs. sham and IPF + TWGT vs. IPF, which were enriched in signaling pathways of interleukin (IL)-17, tumor necrosis factor (TNF), transforming growth factor β (TGF-β), and myofibril. ELISA demonstrated that TWGT downregulated TNF‑α, IL‑1β, IL‑17 (IL-17A), and TGF‑β, and restored epithelial-mesenchymal transition (EMT) markers. Furthermore, TWGT significantly suppressed Th17 cell expansion, and combination with PA enhanced this inhibitory effect. Conclusions:These data show an association between TWGT treatment and changes in the TGF-β/IL-17 axis and Th17 responses, suggesting that this pathway may be involved.