Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

OBJECTIVE: To construct a prediction model for fracture reduction fixator therapy using the multi-modal multi-label classification (MMC) method. METHODS: Medical record data of 818 orthopedic patients from 2019 to 2023 were collected. Medical image features were extracted using the VGG19 network, text features of TCM four diagnostic methods (Inspection, Auscultation & Olfaction, Inquiry, Palpation) were extracted via the MiniLM model, and clinical case features were extracted through a fully connected neural network. After fusing the multi-modal information, multi-label therapy prediction was achieved using a linear layer. RESULTS: Experimental results on the clinical multi-modal dataset showed that the MMC method performed excellently in terms of subset accuracy(SA), accuracy(Acc), precision, and F₁-score, reaching 0.661, 0.856, 0.897, and 0.899 respectively. When the image modality and text modality were removed, the model performance decreased by an average of 8.1% and 2.4% respectively, while the hamming loss(HL) increased by 21.1% and 5.6% respectively. CONCLUSION The fracture reduction fixator therapy prediction model constructed in this study can effectively fuse multi-modal data, accurately predict personalized treatment plans for patients, and significantly improve the accuracy and reliability of treatment decisions. It provides a new solution for the digitalization and intellectualization of Traditional Chinese Medicine(TCM) in fracture treatment and has important clinical application prospects.
Humans ; Female ; Male ; Middle Aged ; Fracture Fixation/methods* ; Adult ; Fractures, Bone/surgery* ; Neural Networks, Computer ; Medicine, Chinese Traditional ; Aged

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Objective To investigate plasma protein expression changes in heatstroke patients using proteomics technology and to identify reliable prognostic biomarkers.Methods A retrospective analysis was conducted on 20 heatstroke patients hospitalized at the 908th Hospital of the Chinese PLA Joint Logistics Support Force from July 2022 to February 2024.Patients were divided into survival(n=16)and death groups(n=4)based on 28-day outcomes.Fasting venous blood samples were collected from both groups for proteomic analysis.Liquid chromatography-mass spectrometry(LC-MS/MS)was used to identify and screen differentially expressed proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed.LASSO regression was applied to screen key prognostic biomarkers,and receiver operating characteristic(ROC)curve analysis was used to evaluate their predictive value.Results A total of 27 upregulated and 90 downregulated proteins were identified between the two groups.These proteins were primarily involved in biological processes such as immune responses,complement activation,and metabolic processes.LASSO regression analysis indicated that actin-related protein 2(ARP2),cysteine-rich scavenger receptor type 1 M130(CD163),and catalase(CAT)could serve as effective biomarkers for evaluating heatstroke prognosis.ROC curve analysis demonstrated that ARP2 had higher diagnostic efficacy(AUC=0.98,sensitivity=0.80,specificity=1.00)compared to CD163(AUC=0.94,sensitivity=0.76,specificity=1.00),CAT(AUC=0.96,sensitivity=0.67,specificity=1.00),and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(AUC=0.79,sensitivity=0.44,specificity=1.00).Conclusion Elevated plasma ARP2 level has good clinical value for predicting poor prognosis in heatstroke patients.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.

Objective To investigate the density,species composition,and seasonal prevalence of domestic rodents in different habitats within Lanzhou garrisons,providing basic information for rodent prevention and control.Methods A total of 12 monitoring sites were sampled across urban,suburban,and rural residential areas from 2014 to 2022.Rodent density was monitored using the night-trapping method in the middle of odd-numbered months.Results From 2014 to 2022,346 domestic rodents were captured using 122 035 effective traps,with an average domestic rodent density of 0.28％.The highest domestic rodent density was 0.63％in 2016,and the lowest was 0.07％in 2020,showing significant differences across years,with an overall trend of initially decreasing and then increasing(χ2=136.555,P<0.001).The dominant species was Rattus norvegicus,accounting for 83.24％of the total rodents captured.Rattus norvegicus accounted for a relatively high proportion across different years,with a statistically significant difference in species composition(χ2=20.931,P<0.05).Rodent densities and species composition also varied significantly among the monitored habitats(P<0.001),with the highest densities observed in rural residential areas and the lowest in urban areas.Seasonal variation in rodent densities showed a bimodal pattern,with smaller peaks in January or March and a larger peak in July.Conclusions Domestic rodent density in Lanzhou garrisons has shown an upward trend in the past few years.Rodent control measures should focus on barracks in rural residential areas,with targeted interventions to reduce the risk of rodent-borne diseases.