This study establishes an integrated research paradigm based on traditional Chinese medicine （TCM） theory， guided by pathological characteristics， centered on formula compatibility principles， and supported by multidisciplinary technologies， to systematically analyze the mechanisms of hepatotoxicity induced by toxic Chinese herbal medicinals and strategies for reducing toxicity through compatibility. The findings revealed that the pathomechanism aligns closely with the "liver aversion to acute irritation" theory from Inner Canon of Yellow Emperor （《黄帝内经》）. The core pathology involves an imbalance between liver's form and function， which is characterized by malnourishment of liver form due to yin-blood depletion and dysfunction in ascending-dispersing and free-flowing activities， and closely linked to modern pathological mechanisms such as microcirculatory disturbances， oxidative stress， inflammatory response， metabolic disorder and gut-liver axis dysregulation. Based on this， a multi-layered compatibility strategy for toxicity reduction is put forward， which involves using sweet medicinals to alleviate urgency， balancing the liver form and its function， and pre-regulating other organs. This provides a theoretical basis for the safe application of toxic Chinese herbal medicinals.

ObjectiveTo investigate the mechanism of Guizhi Fulingwan （GFW） against hepatic fibrosis， focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA （mtDNA）/NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsForty-two male Sprague-Dawley （SD） rats were randomly allocated into six groups （n=7）： control， model， low/medium/high-dose （0.14， 0.28， 0.56 g·kg^-1·d^-1） GFW （GFW-L， GFW-M， GFW-H）， and Dahuang Zhechong pills （DZW， 1.8 g·kg^-1·d^-1）. The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin （HE） staining and Masson's trichrome staining. Transmission electron microscopy （TEM） was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential （MMP， ΔΨ_m） was detected by flow cytometry. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction （Real-time PCR）. The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group， the model group exhibited a decrease in body weight （P<0.01）， an increase in liver index （P<0.01）， elevations in serum ALT and AST levels （P<0.01）， and typical fibrotic features such as disorganized hepatocytes， inflammatory infiltration， and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration， mitochondrial swelling， endoplasmic reticulum expansion， and organelle efflux in the model group. In addition， the model group showed decreased ΔΨ_m （P<0.01）， up-regulated mRNA levels of mtDNA and NLRP3 （P<0.01） and protein levels of NLRP3， Caspase-1， and GSDMD （P<0.01） in the liver tissue， and increased serum levels of IL-1β and IL-18 （P<0.01）. Compared with that in the model group， the body weight increased in GFW-L， GFW-M， and DZW groups （P<0.05） and markedly increased in the GFW-H group （P<0.01）. The liver index decreased in the GFW groups and DZW group （P<0.01）. The serum ALT level declined in the GFW-L group （P<0.05）， and the serum ALT and AST levels decreased in the GFW-M， GFW-H， and DZW groups （P<0.01）. Histopathological damage and fibrosis were alleviated to varying degrees， and TEM revealed mitigated ultrastructural injuries including mitophagy， mitochondrial swelling， and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨ_m increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. The mRNA level of NLRP3 was down-regulated in GFW-M， GFW-H， and DZW groups （P<0.01）. Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group （P<0.01）. The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups （P<0.01）. The protein level of cleaved Caspase-1 was down-regulated in GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. In addition， the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups （P<0.01）. ConclusionGFW can suppress pyroptosis to ameliorate CCl₄-induced hepatic fibrosis， potentially through mitigating mitochondrial damage， inhibiting inflammasome assembly and activation， and blocking pro-inflammatory cytokine release.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

OBJECTIVES: To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification. METHODS: C57BL/6J mice were randomized into blank control group, catalpol group, triptolide group and triptolide+catalpol group. After 13 days of treatment with the agents by gavage, the mice were examined for liver tissue pathology, liver function, hepatocyte subcellular structure, lipid peroxidation, ferrous ion deposition and expressions of ferroptosis-related proteins in the liver. In a liver cell line HL7702, the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions, Fe²⁺ concentration, lipid peroxidation, ROS level and the ferroptosis-related proteins. RESULTS: In C57BL/6J mice, catalpol significantly alleviated triptolide-induced hepatic injury, lowered the levels of ALT, AST and LDH, and reversed the elevation of Fe²⁺ concentration and MDA level and the reduction of GP_X level. In HL7702 cells, inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT, AST and LDH levels. Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11, FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells. CONCLUSIONS The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
Animals ; Phenanthrenes/toxicity* ; Ferroptosis/drug effects* ; Diterpenes/toxicity* ; Epoxy Compounds/toxicity* ; Mice, Inbred C57BL ; Hepatocytes/metabolism* ; Mice ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Iridoid Glucosides/pharmacology* ; Liver/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Male ; Amino Acid Transport System y+/metabolism*

Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

Objective:To investigate the function changes in neurovascular coupling (NVC) in patients with white matter hyperintensities (WMHs) and its correlation with cognitive impairment.Methods:Thirty patients with moderate to severe WMHs admitted to the First People's Hospital of Changzhou from April 2023 to June 2024 (as case group), and 30 subjects with no or mild WMH matched by age, gender and educational level (as the control group) were included prospectively. The general clinical information was collected and cognitive assessment was conducted. Three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) and resting state functional magnetic resonance imaging (rs-fMRI) data were collected to quantify cerebral blood flow (CBF) and functional connectivity strength (FCS). NVC function was evaluated through voxel-wise CBF-FCS correlation analysis. The CBF-FCS coefficients between groups were compared, the correlation between NVC and cognitive function was explored using partial correlation analysis, controlling for the false discovery rate (FDR).Results:The prevalence of hypertension and diabetes in moderate to severe WMHs group was significantly higher than that in the no or mild WMH group (all P<0.05), while the overall cognitive function, executive function and episodic memory function were significantly lower than those in the no or mild WMH group (all P<0.05). There was no significant difference in the CBF-FCS coefficients of the whole brain gray matter between the moderate to severe WMHs group and the no or mild WMHs group. The CBF-FCS coefficients of the bilateral orbital frontal gyrus, right anterior cingulate gyrus, and bilateral hippocampus in the moderate to severe WMHs group were significantly lower than those in the no or mild WMHs group, while the CBF-FCS coefficients of the bilateral parietal gyrus and caudate nucleus were significantly higher than those in the no or mild WMHs group (all q<0.05 after FDR adjustment). Partial correlation analysis showed that after adjusting for age, gender, and education level, the CBF-FCS coefficients of the right anterior and lateral cingulate gyrus were negatively correlated with the executive function completion time in the moderate to severe WMHs group ( r=-0.55, q=0.04 after FDR adjustment), and the CBF-FCS coefficients of the right hippocampus were significantly positively correlated with the episodic memory scores ( r=0.59, q=0.03 after FDR adjustment). These correlations were not statistically significant in the no or mild WMHs group. Conclusion:Patients with moderate to severe WMHs exhibit NVC abnormalities in specific brain regions, which are closely associated with executive function and episodic memory impairment, suggesting that NVC dysfunction may be an important mechanism for WMHs-related cognitive impairment.

Objective: To investigate the efficacy and incidence of adverse reactions of therapeutic erythrocytapheresis in high altitude polycythemia (HAPC) population. Methods: A retrospective study was conducted on 243 HAPC patients who were either native residents or long-term workers in Xizang and underwent therapeutic erythrocytapheresis in the Chengdu Office Hospital of the People's Government of Xizang Autonomous Region from 2021 to 2023. A comparative study was carried out on the changes in blood routine, vital signs, skin color, serum iron metabolism data, and the incidence of adverse reactions before and after the procedure. Results: After erythrocytapheresis, significant decreases were observed in red blood cell (RBC) count (7.06±0.89×10 vs 6.08±0.93×10 /L, P<0.001], hemoglobin (HGB, 211.59±17.99 vs 182.76±19.83 g/L, P<0.001), hematocrit (Hct) [(65.30±6.45)% vs (55.56±8.12)%, P<0.001], serum iron (14.46±4.38 vs 11.77±3.78 μmol/L, P=0.003), total iron-binding capacity (126.62±4.47 vs 123.73±3.77 μmol/L, P=0.002), transferrin (1.88±0.41 vs 1.77±0.12 g/L, P=0.023), transferrin saturation [(11.32±3.11)% vs (9.43±2.78)%, P=0.004], serum ferritin (832.4±295.6 vs 665.3±249.2 ng/mL, P<0.001), systolic blood pressure (123.86±14.43 vs 118.51±13.68 mmHg, P<0.001) and diastolic blood pressure (81.68±9.54 vs 74.28±7.61 mmHg, P<0.001). In contrast, platelet count (Plt, 137.21±46.21 ×10 vs 147.94±50.66 ×10 /L, P<0.001) and oxygen saturation [(93.97±3.29)% vs (95.84±2.27)%, P<0.001] increased. No significant differences were found in white blood cell (WBC) count [5.35 (4.59, 6.44)×10 /L vs 5.43 (4.54, 6.53) ×10 /L, P=0.690], unsaturated iron-binding capacity (112.15±0.50 vs 111.96±0.25 μmol/L, P=0.074) and pulse rate (73.42±11.28 vs 73.19±7.18 beats/min, P=0.750). Furthermore, skin color of the face (conjunctiva, lips) and palms mitigated after therapeutic erythrocytapheresis, changing from purplish-red to red. The total incidence of adverse reactions during erythrocytapheresis was 13.98% (34/243), including citrate toxicity 12.75% (31/243), puncture site hematoma 0.82% (2/243) and blood volume imbalance 0.41% (1/243). Conclusion: Therapeutic erythrocytapheresis could rapidly decrease HCT, Hb, serum iron, transferrin and transferrin saturation levels in HAPC patients, with a low incidence of adverse reactions. Therefore, therapeutic erythrocytapheresis has broad clinical application prospects in Xizang Autonomous Region.

Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the char-acteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians,which has been a major challenge in the global acceptance and application of TCM.Therefore,a standardized TCM prescription system needs to be explored to promote its clinical application.In this study,we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation.We tested its efficacy against intracerebral hemorrhage(ICH).First,the top 100 ICH targets in the GeneCards database were screened according to their relevance scores.Then,SymMap and Traditional Chinese Medicine Systems Pharmacology(TCMSP)databases were applied to find out the target-related ingredients and ingredient-containing herbs,respectively.The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets.The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions.The absorbed components in the serum were detected.In a mouse model of ICH,the new prescription exerted multifaceted effects,including improved neurological function,as well as attenuated neuronal damage,cell apoptosis,vascular leakage,and neuroinflammation.These effects matched well with the core pathological changes in ICH.The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise,multipronged,unbiased,and standardized TCM prescriptions for complex diseases.This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

OBJECTIVE The aim of the study was to investigate and analyze the resource allocation and surveillance status of hospital-associated infections in secondary and above healthcare facilities in Anhui province.METHODS Secondary and above healthcare institutions in 16 cities were selected in Mar.2023 by convenient sampling meth-od,and self-designed questionnaire was administered by'wenjuanxing'to investigate the characteristics of health-care facilities,the management and surveillance of hospital-acquired infections.RESULTS A total of 302 medical facilities,including 88 tertiary and 195 comprehensive facilities,completed the survey.All tertiary healthcare fa-cilities set up the independent departments for hospital-associated infections,while 12.15%of secondary health-care facilities did not.Totally 17.22%of healthcare facilities did not meet the standard requirements of ratio of full-time equivalents to beds,while the unqualified rate of tertiary healthcare facilities(25.00%)was higher than that of secondary healthcare facilities(14.02%).The full-time equivalents were mainly in nursing(64.89%),and relatively insufficient in other specialties.All tertiary healthcare facilities had carried out comprehensive surveil-lance,however,secondary healthcare facilities still needed to be improved.The allocation ratio of surveillance in-formation for system hospital-associated infection was 37.42%in tertiary healthcare facilities,but only 18.69%in secondary.CONCLUSIONS The hospital-associated infection management system of certain healthcare facilities in Anhui province still calls for improving,more personnel numbers and specialties are required.Besides,the con-struction of information system urgently needs to be strengthened.At the same time,more attention should be paid to secondary healthcare facilities,which should be supplied for more resources,carry out basic monitoring work to reduce hospital-associated infections and ensure patients'safety.

OBJECTIVE To evaluate the changes in monitoring indicators related to healthcare-associated infections(HAIs)management in Anhui Province in 2018 and 2022,to provide a scientific basis for optimizing HAI control strategies.METHODS A cross-sectional survey was conducted in 2019 and 2023 across 48 secondary and tertia-ry medical institutions,HAI data were collected and analyzed.RESULTS The two-year averages of monitoring indi-cators were as follows:the incidence rate of HAIs was 0.66％,the prevalence rate of HAIs was 1.69％,the inci-dence rate of surgical site infection for class I incisions was 0.20％,the antibiotic usage rate was 44.59％,the pathogen detection rate for therapeutic antibiotics was 43.76％,the incidence rate of catheter-related blood-stream infection(CRBSI)was 0.64‰,the incidence rate of ventilator-associated pneumonia(VAP)was 5.81‰,and the incidence rate of catheter-associated urinary tract infection(CAUTI)was 0.79‰.By 2022,significant im-provements were observed in most indicators(P＜0.05).Compared to tertiary hospitals,secondary hospitals ex-hibited low rates of hospital infection incidence,prevalence,class I incision infections,antibiotic utilization and CRBSI,but high rates of VAP and CAUTI(P＜0.05).CONCLUSIONS Significant improvements have been made in monitoring indicators related to HAI managements in Anhui Province.However,secondary hospitals still need to enhance their capabilities of monitoring indicators and detecting pathogens.