In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

AIM:To investigate the short-term efficacy of autologous serum eye drops combined with prednisolone acetate in the treatment of severe dry eye with grade II-III corneal injury.METHODS:Prospective, randomized, controlled single center study. Totally 122 patients(122 eyes, all enrolled patients had bilateral disease, with the more severely affected eye selected as the study eye; if the severity was similar between both eyes, the right eye was chosen as the study eye)with severe dry eye and grade II-III corneal injury who were treated at Wuhan University Affiliated Aier Eye Hospital from March 2023 to March 2025 were randomly divided into a control group(treated with sodium hyaluronate eye drops combined with autologous serum eye drops)and an observation group(treated with sodium hyaluronate eye drops, autologous serum eye drops combined with prednisolone acetate eye drops)using a random number table method. After continuous administration for 2 wk, the tear inflammatory reaction [interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)], subjective symptoms [ocular surface disease index(OSDI)score], lacrimal gland function [tear film break-up time(TBUT)and Schirmer tear secretion test(SⅠt)], corneal injury degree [corneal fluorescein staining(CFS)score] and corneal nerve function [total number and density of corneal subepithelial nerve(SBN)] before and after treatment were compared between the two groups, and the occurrence of adverse reactions during treatment was recorded. RESULTS:All patients have completed follow-up. The control group consisted of 61 cases and 61 eyes, with 24 males and 37 females, with an average age of 43.87±5.12y. There were 61 cases and 61 eyes in the observation group, including 21 males and 40 females, with an average age of 42.15±4.76y. At 1 and 2 wk after treatment, the levels of IL-6 and TNF-α in tears, OSDI score, and CFS score of the two groups were significantly lower than those before treatment, and those in the observation group were lower than those in the control group(all P<0.05). The total number of TBUT, SⅠt, SBN, and SBN density in both groups of patients increased significantly compared to before treatment, and the observation group was higher than the control group(all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups of patients during treatment(P=0.717).CONCLUSION:The combination of autologous serum eye drops and prednisolone acetate is effective in treating severe dry eye with grade II-III corneal injury. It can reduce patients' inflammatory reactions, subjective symptoms, and degree of corneal injury, promote the improvement of lacrimal gland function and corneal nerve function, providing a new strategy for corneal nerve repair. Furthermore, the combination therapy does not increase the risk of adverse reactions and shows good safety in short-term application.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective: To explore whether digital facial and tongue diagnostic technologies can support the assessment of coronary heart disease (CHD) patients for coronary artery stenosis severity, and examine potential associations between digital tongue diagnosis features and myocardial biomarkers. Methods: The TFDA-1 face and tongue diagnosis instrument and the TDAS analysis system were used to perform intelligent visual examination and analysis of the facial and tongue in CHD patients who attended the Department of Cardiology at Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine between October 2, 2023 and July 31, 2024. Variables were screened using principal component analysis (PCA) and multicollinearity analysis to construct four machine learning models, including random forest, LightGBM, decision tree, and naive Bayes, for the early prediction of coronary artery stenosis severity. Model performance metrics, including sensitivity, specificity, precision, F1 score, accuracy, and the area under the receiver operating characteristic (ROC) curve (AUC), were evaluated. Visual analyses were performed using the SHapley Additive exPlanations (SHAP) interpreter and decision curve analysis. For patients after percutaneous coronary intervention (PCI), a conceptual model linking cardiac biomarkers and tongue diagnosis was constructed using the partial least squares structural equation modeling (PLS-SEM), and its validity was assessed. Results: A total of 459 CHD patients were enrolled and assigned to a PCI group and a non-PCI group (which comprised two subgroups: mild stenosis or less group, moderate stenosis or greater group). For sublingual vein (SV) features, the PCI group had lower SV-a and SV-b than the other groups (P < 0.01 and P < 0.05, respectively). For tongue surface features, the PCI group had significantly higher tongue body (TB)-L, TB-a, and TB-b (P < 0.05, P < 0.01, and P < 0.001, respectively), as well as higher tongue coating (TC)-a and TC-b (P < 0.01 and P < 0.001, respectively). Age, SV-a, SV-b, creatine kinase-myocardial band (CK-MB), CK, TC-a, lip-L, and lip-b were incorporated in the machine learning models. The random forest model performed best, with an AUC of 0.924, an F1 score of 0.839, precision of 0.807, accuracy of 0.864, sensitivity of 0.873, and specificity of 0.839. Decision curve analysis indicated that both LightGBM and random forest had clinical utility. PLS-SEM confirmed the pathway relationships: myocardial biomarkers → TB and myocardial biomarkers → TC (coefficient = – 0.238, t = 2.239, P = 0.025, and coefficient = – 0.270, t = 2.522, P = 0.012, respectively). Conclusion This study developed a noninvasive early warning model for coronary artery stenosis in patients with CHD. It applied PLS-SEM to investigate the association between post-PCI cardiac biomarkers and tongue diagnosis, and validated the proposed association chain. These findings suggest that intelligent traditional Chinese medicine (TCM) visual diagnosis integrated with modern digital technology may support CHD risk assessment and comprehensive health management.

Objective To explore the feasibility and safety of using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules during thoracoscopic wedge resection. Methods Patients who underwent CT-guided percutaneous lung puncture injection of localization agents to locate lung nodules at the First Affiliated Hospital of Fujian Medical University from November 2023 to January 2024 were selected. Under thoracoscopy, lung nodules were located by white light mode, fluorescence mode, or near-infrared mode and wedge resection was performed. The feasibility of using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules was preliminarily verified by evaluating whether the localization agent concentrated around the nodules, and the safety of this method was verified by analyzing the incidence of adverse reactions during patient puncture and surgery. Results A total of 30 patients with lung nodules were included, including 10 males and 20 females, with an average age of (55.5±11.2) years. In 26 patients, the amount of localization agent used was moderate, the localization agent concentrated around the nodules, and successful precise localization of small lung nodules was achieved. In 4 patients, due to excessive use of localization agent, the marker was diffuse with pleural staining. The overall localization success rate was 86.7%, and when the injection volume of localization agent was 0.2-0.5 mL, the localization success rate was 100.0%. All patients successfully completed thoracoscopic wedge resection and found nodule lesions, with negative margins and a distance from the margin to the lesion that met the requirements. There were no complications. Conclusion Thoracoscopic surgery using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules is safe and feasible.

Objective To investigate the prognosis and satisfaction of the R2 intervention procedure and develop related predictive models. Methods The clinical data of 64 patients with primary craniofacial hyperhidrosis who underwent R2 intervention surgery at the First Affiliated Hospital of Fujian Medical University from November 2018 to October 2022 were retrospectively analyzed. By statistically analyzing the risk factors for compensatory hyperhidrosis (CH) and satisfaction, and conducting feature screening, a relevant prediction model was established. Results Finally, 51 patients were collected, including 43 (84.3%) males and 8 (15.7%) females, with an average age of (30.27±7.22) years. Overall postoperative satisfaction was high, with only 5.9% of patients expressing regret about the surgery. However, 92.2% of patients experienced CH. The onset of postoperative CH was most prominent within the first 3 months postoperatively, with the incidence rate stabilizing thereafter. Preoperative heart rate and R2 sympathetic nerve clipping were identified as independent risk factors for severe CH. The preoperative body mass index, the degree of sweating in the chest and abdomen, are significantly correlated with postoperative satisfaction. Conclusion The R2 intervention surgery effectively alleviates the symptoms of primary craniofacial hyperhidrosis, and patient satisfaction is high.