ObjectiveTo investigate the effects of Shengui Jiangtang Formula on insulin resistance and glucose-lipid metabolism in spontaneous type 2 diabetic db/db mice based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box protein O1 （FoxO1） signaling pathway， and to provide theoretical foundation for its clinical application through fundamental experiments. MethodsA randomized controlled design was employed in this study. Thirty spontaneous type 2 diabetic db/db mice meeting the inclusion criteria （fasting blood glucose >7.0 mmol·L^-1 and random blood glucose on a different day≥11.1 mmol·L^-1） were selected as the subjects. After stratified block randomization by body weight and blood glucose levels， they were randomly assigned to a model group， a metformin group， and a Shengui Jiangtang formula group， with n=10 per group. Ten db/m mice were used as the normal group. During the 5-week intervention， general indicators （including general condition， fasting blood glucose （FBG）， body weight， and food intake） were recorded weekly. An oral glucose tolerance test （OGTT） was performed at week 5. After 5 weeks， serum was collected to measure glucose-lipid metabolism parameters. Liver tissues were analyzed as follows： Histopathology was observed through hematoxylin and eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Oil red O staining. The expression of proteins and genes related to the PI3K/Akt/FoxO1 signaling pathway was quantitatively analyzed using Western blotting （Western blot） and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsGeneral observations： The mice in the normal group were generally healthy， exhibited agile responses and had smooth and glossy fur. Compared with the normal group， the mice in the model group displayed typical symptoms of polydipsia， polyphagia， and polyuria， along with listlessness and rough fur. Their food intake， initial body weight， liver weight， and liver index were all significantly higher than those in the normal group （P<0.01）. After 5 weeks of drug intervention， neither the Shengui Jiangtang Formula group nor the metformin group significantly affected the food intake of the model mice. Compared with the model group， no statistically significant difference was observed in liver weight or liver index in the Shengui Jiangtang formula group. Serum biochemical indicators： Compared with the normal group， the model group showed significantly elevated levels of FBG， fasting insulin， homeostatic model assessment of insulin resistance （HOMA-IR）， glycosylated serum protein， and blood lipids. After drug intervention， compared with the model group， the Shengui Jiangtang formula group significantly reduced FBG in the model mice （P<0.01）. The blood glucose levels at all time points during the OGTT in the Shengui Jiangtang Formula group were lower than those in the model group， with statistically significant differences in the 0 min blood glucose and the area under the curve for glucose compared to the model group （P<0.05）. Furthermore， the formula significantly reduced fasting insulin levels， HOMA-IR， and glycosylated serum protein levels （P<0.05）. It also showed a tendency to decrease blood lipids， liver enzymes （aspartate aminotransferase， alanine aminotransferase）， and blood urea nitrogen levels， and a tendency to increase creatinine levels， although these differences were not statistically significant. Liver histomorphology： HE staining indicated that Shengui Jiangtang formula improved the morphological structure of hepatocytes and attenuated steatosis in diabetic mice. Liver PAS staining showed that it increased hepatic glycogen content and promoted hepatic glycogen synthesis in diabetic mice. Oil red O staining demonstrated that it reduced lipid deposition within hepatocytes. Western blot： Compared with the normal group， the model group showed decreased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and increased FoxO1 protein expression. Compared with the model group， both the metformin and Shengui Jiangtang Formula groups showed increased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and decreased FoxO1 protein expression. Real-time PCR： Compared with the normal group， the mRNA expression of PI3K and Akt was downregulated （P<0.05）， and the mRNA expression of FoxO1 was downregulated （P<0.05） in the model group. ConclusionShengui Jiangtang Formula can improve insulin resistance and glucose-lipid metabolic disorders in db/db mice. It alleviates hepatic steatosis， promotes hepatic glycogen synthesis， and reduces lipid deposition in these mice. The mechanism by which Shengui Jiangtang Formula improves insulin resistance may be associated with the PI3K/Akt/FoxO1 signaling pathway.

Diabetic foot ulcer （DFU） is one of the most severe and costly complications of diabetes， with its refractory nature largely attributed to the persistent vicious cycle of inflammation and oxidative stress. Conventional single-target therapeutic strategies often fail to effectively break this cycle. Traditional Chinese medicine （TCM）， leveraging its unique philosophy of ''holistic regulation and multi-target intervention''， has demonstrated significant advantages in promoting DFU healing. This review introduced a ''systemic intervention'' perspective to systematically elucidate how TCM， through multi-component synergistic networks， precisely deconstructs and intervenes in this pathological loop. Firstly， this study provided an in-depth analysis of how， under hyperglycemic conditions， the crosstalk between the nuclear factor-kappa B （NF-κB） and NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） inflammasome pathways， the imbalance in macrophage polarization and the disruption of redox homeostasis interact to form a self-sustaining vicious cycle that impedes wound repair. Subsequently， the core content systematically discussed the strategies by which TCM breaks this deadlock： （1） Active ingredients from single herbs （e.g.， luteolin and astragaloside Ⅳ） can precisely modulate key nodes such as the phosphatidylinositol 3‑kinase/protein kinase B （PI3K/Akt） and TLR4/NF-κB pathways， thereby suppressing inflammation and oxidative stress. （2） Classical compound formulas （e.g.， Simiao Yong'an decoction and Taohong Siwu decoction） synergistically improve microcirculation and the immune microenvironment through multi-component cooperation. （3） External preparations （e.g.， Shengji Yuhong Ointment and Jinhuang powder） potently exert local anti-inflammatory and pro-repair effects by activating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase 1 （Nrf2/HO-1）. Collectively， these three modalities embody a synergistic mechanism characterized by ''internal treatment modulating the internal milieu to address the root cause， and external treatment targeting the lesion to alleviate symptoms''.” Existing clinical evidence has confirmed that the aforementioned multi-target interventions can effectively promote healing and improve symptoms. However， this field still faces persistent challenges， including an unclear material basis for the efficacy of compound formulas， and insufficient standardization in quality control and clinical protocols. These challenges stem from the inherent tension between the complex systems-based characteristics of TCM and the requirements of modern standardization. Future efforts urgently require to leverage cutting-edge technologies， such as network pharmacology， spatial multi-omics， and artificial intelligence to propel the paradigm shift in the prevention and treatment of DFU with TCM from ''empirical multi-target approaches'' toward ''precise systems regulation''. This will provide a theoretical foundation for developing innovative strategies for managing difficult-to-heal wounds based on an integrated traditional Chinese and Western medicine approach.

OBJECTIVE To evaluate the anticoagulant efficacy and safety of nafamostat mesylate （NM） in the treatment of uremic patients at high risk of bleeding undergoing continuous veno-venous hemofiltration （CVVH） with different methods （pre- dilution and post-dilution）. METHODS A total of 130 uremic patients at high risk of bleeding who underwent CVVH treatment in the nephrology department of Chongqing University Three Gorges Hospital from July 2023 to September 2024 were selected. They were divided into pre-dilution group and post-dilution group according to the random number table method， with 65 cases in each group. Both groups of patients received CVVH treatment under NM anticoagulation. The pre-dilution group adopted the pre-dilution replacement method， while the post-dilution group adopted the post-dilution replacement method. The coagulation， pressure， and usage duration of the filter and dialysis circuit venous reservoirs were compared between the two groups. The changes in prothrombin time （PT）， prothrombin time-international normalized ratio （PT-INR）， activated partial thromboplastin time （APTT）， and fibrinogen （FIB） in the peripheral venous blood before the heparin pump and after the filter at 1， 4 and 7 h of CVVH treatment， as well as 20 min after the end of treatment， were compared between the two groups. The single-compartment urea clearance rate （spKt/V）， β2-microglobulin （β2-MG） clearance rate and the incidence of adverse reactions were duni2007@foxmail.com compared between the two groups. RESULTS Both the pre-dilution and post-dilution groups had 60 patients who completed the study. The incidence of grade Ⅱ-Ⅲ coagulation of the filter and venous reservoirs， as well as the number of patients with transmembrane and venous pressure alarm intervention in the post- dilution group were significantly higher or more than those in the pre-dilution group （P＜0.05）， while usage time of the filter and the pipeline in the post-dilution group was significantly shorter than that in the pre-dilution group （P＜0.05）. The APTT values before the heparin pump as well as PT and APTT values after the filter at 1 h， 4 h， and 7 h of CVVH treatment in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There were no significant differences in PT， PT- INR， APTT and FIB between the two groups of patients 20 min after the end of treatment （P＞0.05）. The spKt/v and β2-MG clearance rates in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS When NM is used as an anticoagulant in the CVVH treatment of uremic patients at high risk of bleeding， compared with the pre-dilution treatment method， the post-dilution treatment method has a higher incidence of filter and dialysis tubing venous reservoir， a shorter usage time of the filter and pipeline， and a greater impact on extracorporeal coagulation， but has a higher solute clearance rate. Clinically， different dilution methods can be selected according to the different treatment needs of patients.

The promulgation of the Technical Specifications for Clinical Use of Blood (2025 Edition) signifies that China's clinical blood transfusion management has transitioned from mere technical operations to a new stage centered on patient blood management (PBM). Through an in-depth comparison of the new and old specifications, this paper analyzes the core transformations regarding conceptual reconstruction, legal alignment, technological upgrades, and closed-loop management. The new specifications establish PBM principles, reinforce legal safeguards for informed consent and emergency treatment, and construct a comprehensive, refined quality control system by specifying compatibility testing standards and introducing a post-transfusion evaluation system. Medical institutions should seize this opportunity to update management protocols and information systems, deepen multidisciplinary collaboration, and drive the profound transformation of clinical blood use from focusing solely on safety assurance to placing equal emphasis on science and value.

OBJECTIVE To confirm trigger items for adverse drug reaction （ADR） induced by bevacizumab， to identify and analyze the occurrence of related ADR， and to establish a predictive model for severe adverse reaction （SAR） caused by this drug. METHODS Based on the global trigger tool （GTT） theory， and referencing the GTT White Paper， drug package inserts and relevant literature， trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items， electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects （divided into training and test sets at a ratio of 7∶3）， candidate feature variables were selected from 39 related variables using the Boruta algorithm， and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features， Logistic Regression， Extreme Gradient Boosting， Light Gradient Boosting Machine， Random Forest， and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve （AUC） of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations （SHAP） method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined， comprising 17 laboratory indicators， 13 clinical manifestations， and 8 intervention measures. In total， 483 patients with positive trigger items were included， and 318 patients with bevacizumab-induced ADR were identified， including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% （708/1 625） and 63.84% （318/483）， respectively. Bevacizumab-induced ADR involved 7 systems/organs， with the hematological system being the most frequently involved （64.15%）. The Boruta algorithm selected 7 vari ables： serum potassium， hematocrit， albumin-to-globulin ratio， prealbumin， hypertension history， age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR （OR＝0.234， P ＝0.002）， while a history of hypertension （OR＝2.642， P ＝0.006） and increased age （OR＝1.040， P ＝0.025） were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC， F1 score and recall rate （0.761， 0.447， 0.607）， compared to other models. SHAP evaluation results indicated that variables such as serum potassium， hematocrit， and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR， whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.

Dry eye （DE） is a prevalent multifactorial disease of the ocular surface， clinically characterized by tear film homeostasis imbalance accompanied by related ocular surface symptoms. Specifically， the tear film is a thin liquid layer of tears covering the cornea and conjunctiva through blinking， while tear film homeostasis serves as the foundation for maintaining normal ocular surface structure and function. Insufficient tear secretion and excessive tear film evaporation lead to tear hyperosmolarity and the production of inflammatory mediators， disrupting tear film homeostasis and subsequently forming DE. Additionally， cascade reactions are triggered， resulting in a "vicious cycle of DE" that exacerbates the disease severity and prolongs its duration. Therefore， for DE treatment， it is crucial to restore tear film homeostasis and terminate this vicious cycle. Traditional Chinese medicine （TCM）， which differentiates and treats DE based on systemic conditions， often achieves favorable therapeutic outcomes， offering additional treatment options for DE. Studies have demonstrated that TCM can alleviate DE by regulating tear film homeostasis and terminating the vicious cycle. This review systematically summarizes recent basic experimental research in China and abroad on TCM in alleviating DE by regulating tear film homeostasis， aiming to provide a theoretical basis for clinical treatment and an insight for research design.

OBJECTIVE To evaluate the clinical comprehensive value of four Chinese patent medicines （Xuezhikang， Zhibitai， Zhibituo， Jiangzhiling） in the treatment of hyperlipidemia， and provide a reference for rational clinical drug use. METHODS A clinical comprehensive evaluation index system was established in accordance with the Evidence and Value： Impact on Decision-Making （EVIDEM） framework and Technical Guideline for Clinical Comprehensive Evaluation of Cardiovascular Drugs （2022 edition， trial implementation）. CNKI， Wanfang data， VIP， PubMed， ScienceDirect， Embase and official websites were retrieved to collect the literature such as drug instructions， guidelines and consensus statements， and systematic reviews/meta-analyses for the four Chinese patent medicines. A comprehensive evaluation was conducted from seven dimensions： effectiveness， safety， economy， suitability， accessibility， innovation and characteristics of traditional Chinese medicine. RESULTS This evaluation index system included 7 first-level indicators， 15 second-level indicators and 30 third-level indicators. Xuezhikang achieved the highest comprehensive evaluation score of 81.4 points， and was classified as class Ⅰ recommendation. Zhibitai with 76.0 points and Zhibituo with 60.9 points were both classified as class Ⅱ recommendation. Jiangzhiling with 48.8 points was classified as class Ⅳ recommendation. CONCLUSIONS Xuezhikang demonstrates the optimal clinical comprehensive value for treating hyperlipidemia. Zhibitai exhibits certain advantages in terms of safety and characteristics of traditional Chinese medicine； Zhibituo shows a moderate performance in all aspects； Jiangzhiling has a relatively low score. Appropriate medicines can be selected clinically according to actual conditions and patients’ characteristics.

BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.