It is believed that diabetes complicated with coronary heart disease is closely related to the functional interplay of the heart， spleen， and kidneys. This paper proposed the concept of the heart-spleen-kidney as a unified system for understanding and treating the disease. At the early stage， spleen and kidney deficiency leads to the internal accumulation of phlegm， dampness， and turbid lipids， causing impaired blood circulation and vascular obstruction， so treatment should focus on tonify the kidneys and strengthening the spleen， activating blood circulation and resolving stasis， using the self-prescribed Tangxin Maiwen Formula （糖心脉温方）. As the disease progresses， further decline of spleen and kidney function results in inadequate nourishment of the heart， leading to blood stasis and the accumulation of phlegm， dampness， and turbid lipids， which may transform into pathogenic heat and toxins， causing heart damage， then treatment should emphasize on boosting qi and nourishing yin， clearing heat， activating blood and resolving toxins， using the self-prescribed Tangxin Maiqing Formula （糖心脉清方）. In advanced stages， three zang organs， the heart， spleen， and kidneys， become severely impaired， leading to mental activity fail to be nourished and abnormal cognitive functions， so treatment should focus on harmonizing the three zang organs simultaneously， using the self-prescribed Yunpi Tiaoxin Decoction （运脾调心汤）. This approach aims to provide a clinical framework for the diagnosis and treatment of diabetes with coronary heart disease.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

ObjectiveThe primary objective of this study was to investigate the effects of carbohydrate intake order on post-exercise recovery and metabolic regulation under heat stress, particularly in models of exercise induced fatigue. Given the increasing significance of optimizing nutritional strategies to support performance in extreme environmental conditions, this study aimed to provide experimental evidence that contributes to a better understanding of how the sequence in which carbohydrates are consumed impacts exercise recovery, metabolic homeostasis, and fatigue alleviation in a high-temperature environment. MethodsA mouse model of exercise-induced fatigue was established under high-temperature (35°C) to simulate heat stress. The subjects were divided into 3 distinct groups based on their carbohydrate intake order: the “mixed intake” group (HOT_MIX), where all macronutrients (carbohydrates, proteins, and fats) were consumed in a balanced ratio; the “carbohydrate-first intake” group (HOT_CHO), where carbohydrates were consumed first followed by other macronutrients; the “carbohydrate-later intake” group (HOT_PRO), where proteins and fats were consumed prior to carbohydrates. Each group underwent a 7 d intervention period with daily intake according to their designated group. Exercise performance was assessed using rotarod retention time test, and biomarkers of muscle damage, such as lactate dehydrogenase (LDH), creatine kinase (CK), lactate (LD), alanine aminotransferase (ALT), and non-esterified fatty acids (NEFA), were measured. Furthermore, targeted metabolomics analyses were conducted to investigate metabolic shifts in response to different dietary strategies, and KEGG pathway enrichment analysis was employed to explore the biological mechanisms underlying these changes. ResultsThe findings demonstrated that the HOT_PRO group exhibited a significantly improved performance in the rotarod test, with a longer retention time compared to both the HOT_MIX and HOT_CHO groups (P<0.05). Additionally, this group showed significantly reduced levels of muscle damage markers such as LDH and CK, indicating that the carbohydrate-later intake strategy helped alleviate exercise-induced muscle injury. Metabolomic profiling of the HOT_PRO group showed marked increases in alanine, creatine, and flavin adenine dinucleotide (FAD), indicating shifts in amino acid metabolism and oxidative metabolism. Conversely, metabolites such as spermidine, cholesterol sulfate, cholesterol, and serine were significantly reduced in the HOT_PRO group, pointing to alterations in lipid and sterol metabolism. Further analysis of the differential metabolites revealed that these changes were primarily associated with key metabolic pathways, including glycine-serine-threonine metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, and steroid hormone biosynthesis. These pathways are essential for energy production, antioxidant defense, and muscle recovery, suggesting that the carbohydrate-later feeding strategy may promote metabolic homeostasis and improve exercise recovery by enhancing these critical metabolic processes. ConclusionThe results of this study support the hypothesis that consuming carbohydrates after proteins and fats during exercise recovery enhances metabolic homeostasis and accelerates recovery under heat stress. This strategy effectively modulates energy, amino acid, and lipid-related pathways, which are crucial for improving endurance performance and mitigating fatigue in high-temperature environments. The findings suggest that carbohydrate-later intake could be a promising nutritional strategy for athletes and individuals exposed to heat during physical activity. Furthermore, the study provides valuable insights into how different nutrient timing strategies can impact exercise recovery and metabolic regulation, paving the way for more personalized and effective nutritional interventions in extreme environmental conditions.

ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Objective:To evaluate the effect of virtual reality arthroscopic simulation system combined with case-based learning (CBL) in orthopedic clinical teaching.Methods:From January 2021 to June 2022, a total of 36 residents who took the standardized residency training at Department of Articular Orthopedics in The Third Affiliated Hospital of Soochow University were enrolled in this study. They were randomized into an experimental group and a control group, with 18 trainees in each group. The experimental group adopted the virtual reality arthroscopic simulation system combined with CBL teaching mode, while the control group adopted simple endoscopic simulation training box with traditional teaching mode. Theoretical and practical tests and questionnaire survey were carried out to evaluate the teaching effects in two groups. SPSS 22.0 was performed to conduct t-test on the measurement data between the two groups. Results:The theoretical and practical test scores of the experimental group [(89.39±3.09) and (82.72±4.28)] were better than those of the control group [(86.22±4.43) and (76.61±5.65)], with statistically significant differences ( t= 2.49, P=0.018; t=3.66, P=0.001). The questionnaire survey showed that the experimental group was better than the control group in creating novel forms of courses [(4.94±0.24) vs. (4.11±0.58), t=5.62, P<0.001], simulating more real scenes [(4.83±0.38) vs. (3.78±0.43), t=7.80, P<0.001], inspiring learning interests [(4.78±0.43) vs. (4.00±0.59), t=4.51, P<0.001], improving practical skills [(4.83±0.38) vs. (3.83±0.51), t=6.61, P<0.001], and building career confidence [(4.50±0.62) vs. (3.06±0.54), t=7.47, P<0.001], with statistically significant differences (all P<0.001). Conclusions:The virtual reality arthroscopic simulation system combined with CBL teaching mode can better simulate the real clinical scenes, help inspire the interest of learning and quickly improve practical skills, thereby improving the effect of orthopedic clinical teaching.

Aim To compare the pharmacokinetics of pemirolast potassium tablets in healthy subjects in Chi-na under single fasting and postprandial conditions,and to evaluate the bioequivalence of the test prepara-tion(T)and the reference preparation(R).Methods A randomized,open-ended,single-dose,two-cycle,double-cross bioequivalence trial design was adopted,and 26 and 30 subjects were enrolled in the fasting group and the postprandial group,respectively,and 10 mg of the test preparation and the reference preparation were taken in the fasting or postprandial state each cy-cle,and venous blood was collected at the designed time points before and after the administration cycle.The concentration of pemirolast potassium in plasma was determined by LC-MS/MS method,and the phar-macokinetic parameters were calculated with PhoenixTM WinNonlin ?(8.3)software,and the bioequivalence analysis of the two preparations was performed.Re-sults The t1/2 of the test preparation and the reference preparation was(4.44±0.91)h and(4.49±0.93)h,respectively;the median tmax was(1.96±1.29)h and(2.18±1.25)h,respectively;the Cmax was(867.12±205.56)μg·L-1 and(863.35±172.03)μg·L-1,respectively;the AUC0-t was(5 513.23±1463.67)h·μg·L-1 and(5 661.32±1 628.65)h·μg·L-1,respectively;AUC0_∞ was(5 699.81±1477.68)h·μg·L-1 and(5 849.44±1 644.75)h·μg·L-1,respectively.The statistical results of the 90％confidence intervals of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞ was 92.49％～107.53％,94.71％～100.67％and 95.28％～100.27％,respectively,all of which were within the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach.The t1/2 of single oral administration after prandial administra-tion of the tested preparation and the reference prepara-tion was(4.46±0.78)and(4.51±0.84)h,respec-tively;the median tmax was(3.08±1.36)h and(3.28±1.28)h,respectively;the Cmax was(683.83±111.87)μg·L-1 and(689.77±110.24)μg·L-1,respectively;the AUC0-t was(5 695.99±1566.05)h·μg·L-1 and(5 773.60±1 551.04)h·μg·L-1,respectively;the AUC0-∞ was(5 914.06±1 551.86)h·μg·L-1 and(5 967.30±1552.89)h·μg·L-1,respectively.The 90％confi-dence interval of Cmax,AUC0-t,and AUC0-∞ was 93.56％～104.69％,96.43％～100.83％,and 97.29％～101.14％,respectively,which was in the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good after meals.Conclusion In the state of fasting and postprandial single oral administration,the two kinds of pemirolast potassium tablets have good bio-equivalence.

Objective:To establish a bacterial endotoxin test method for nafamostat mesilate for injection.Methods:The interference test of the bacterial endotoxin test method-kinetic chromogenic assay was carried out according to the Chinese Pharmacopoeia 2020 Volume Ⅳ general chapter 1143.Results:The interference effect of naphtholimus mesylate can be effectively eliminated by treating the test solution with an alkaline regulator for a certain period of time and diluting it.Conclusion:The bacteria endotoxin test-kinetic chromogenic assay for nafa-mostat mesilate for injection is applicable.