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.

Malonylation is an important post-translational modification of proteins.In this work,a comprehensive malonylation proteomics study on hepatocellular carcinoma(HCC)tumorous and non-tumorous tissues using antibody enrichment combined with high performance liquid chromatography-mass spectrometry for discovery of early diagnostic biomarkers or potential new drug targets of HCC was performed.A total of 1299 malonylated peptides containing 1064 malonylated sites were identified from HCC tissues,corresponding to 511 malonylated proteins.Quantitative results showed that 56 and 80 malonylated proteins were up-regulated and down-regulated in HCC tissues,including 60 and 101 malonylated sites,respectively.Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis showed that these differentially modified proteins were involved in various important pathways such as metabolic pathways,fatty acid degradation,and glycolysis/gluconeogenesis.As a key enzyme in glycolysis/gluconeogenesis,phosphoenolpyruvate carboxykinase 1(PCK1)was malonylated at lysine 244(K244)and the malonylation was only detected in HCC tumorous tissues.More importantly,the K244 site served as a binding site for Mn2+and highly conserved across different species.Therefore,it could speculate that the malonylation of K244 would affect its activity and played a role in liver cancer by affecting its binding with Mn2+,which requied further verification through site mutation experiments.Western blot analysis by malonylation pan antibody showed that the malonylation level reduced markedly in HCC tumorous tissues compared with adjacent non-tumorous tissues,which was consistent with mass spectrometry data.In addition,the proliferation and invasion of PLC/PRF/5 cell was significantly inhibited and protein malonylation level was increased obviously when treated with sodium malonate.All the evidence indicated that protein malonylation played an important role in HCC pathogenesis,and its molecular mechanism deserved further investigation.Furthermore,the 136 differentially malonylated proteins provided rich source of candidate targets for further research on HCC pathogenesis.

Objective To construct a competency evaluation model for forensic practitioners,providing a reference for their training and assessment.Methods Based on the iceberg and onion models of com-petency,and with reference to Spencer's Competency Dictionary,literature research was conducted and focus group interviews were employed to preliminarily construct core indices and measurement items for evaluating the competency of forensic practitioners.The Delphi method was applied for two rounds of expert consultation to further refine the competency evaluation index system.The analytic hierarchy process(AHP)was used to calculate the weights of the indices.Results A competency evaluation model for forensic practitioners was constructed,consisting of 7 core indices,encompassing forensic skills,identification service capabilities,and the ability to apply relevant legal knowledge and 49 mea-surement items.The weights of the core indices and measurement items were determined.Conclusion The constructed competency evaluation model for forensic practitioners is scientifically sound and inno-vative,and has unique characteristics of forensic medicine compared with other medical models.

Objective:To explore the applicability of endoscopic retrograde appendicitis therapy (ERAT) and methods of aeromedical assessment of military flying personnel with appendicitis.Methods:The diagnosis, ERAT process and aeromedical assessment of 2 military flying personnel with appendicitis were analyzed while the related literature was reviewed.Results:Two military flying personnel diagnosed with appendicitis underwent ERAT after appendiceal perforation or intra-abdominal infection was ruled out. Abdominal pain was resolved within one day of ERAT while inflammatory markers were normalized within one week. Both patients returned to flight duties 1-2 weeks after the procedure. During a follow-up of over one year, both remained excellent in flight performance.Conclusions:For military flying personnel with uncomplicated appendicitis, ERAT is a safe and effective treatment. Patients can return to flight duties within 1-2 weeks of resolution of postoperative abdominal pain symptoms. Compared with traditional appendectomy, ERAT can shorten the grounding time for military flying personnel.

Objective To investigate the correlation between dual-energy computed tomography angiography(CTA)parameters of carotid plaques and acute stroke events.Methods A retrospective analysis was conducted on the clinical and imaging data of patients who underwent dual-energy head and neck CTA and brain MRI scans.Utilizing the Siemens workstation(Syngo.Via VB40B),region of interest(ROI)were placed on the thickest slice of the carotid plaque in the axial plane to obtain parameters such as fat fraction(FF),virtual non-contrast(VNC)value,iodine concentration(IC),electron density(Rho),effective atomic number(Zeff),dual energy index(DEI),spectral curve,and corresponding CT values at 40 keV(40 keVHU)and 90 keV(90 keVHU).The slope of the energy spectrum curve(λ)was calculated within the 40 keV-90 keV range.Patients with acute cerebral infarction(ACI)in the ipsilateral anterior circulation territory were classified into the ACI group,while those without were classified into the non-acute cerebral infarction(NACI)(NACI group).Qualitative data were analyzed using the x2 test,and quantitative data were analyzed using the t-test.The predictive performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,and the differences between different ROC curves were compared using the DeLong test.Results A total of 72 patients were included,with 21 in the ACI group and 51 in the NACI group.The mean values of FF,Zeff,and 40 keVHU in the ACI group were greater than those in the NACI group.Statistically significant differences were observed between the groups for Zeff,DEI,40 keVHU,and λ(P＜0.05).40 keVHU demonstrated the highest predictive performance,and the AUC,sensitivity,and specificity was 0.789,81.0％,and 74.5％,respectively.A combined variable constructed through logistic regression analysis yielded an AUC,sensitivity,and specificity of 0.796,85.7％,and 70.6％,respectively,with no significant statistical differences compared to single factor variables.Conclusion Dual-energy CTA parameters of carotid plaques may aid in predicting intraplaque hemorrhage(IPH)and the occurrence of acute stroke events.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Objective:To explore the impact of plant and animal dietary behaviors on type 2 diabetes mellitus (T2DM) in older adults aged ≥65 in 18 longevity areas of China.Methods:The subjects were 5 223 older adults over 65 years old from the Healthy Ageing and Biomarkers Cohort Study (HABCS) in 18 longevity areas in China. Through a questionnaire survey and physical examination, information about their demographic characteristics, lifestyles, daily activities, self-health status, current diseases, and fasting venous blood were collected. Food Frequency and Questionnaire (FFQ) was used to collect data on food intake frequency. Based on the prior method, the plant-based diet index (PDI) and animal-based diet index (ADI) of 5 223 older adults were calculated. Subjects were divided into three groups (low-level group: PDI<39 or ADI<31, middle-level group: 39≤PDI≤42 or 31≤ADI≤34, high-level group: PDI>42 or ADI>34) by tertiles of PDI and ADI. Multivariate logistic regression was used to analyze the association between PDI and ADI and the risk of T2DM.Results:The average age of 5 223 subjects was (84.8±11.5) years, with the median ( Q1, Q3) of PDI about 41(38, 43) and the median ( Q1, Q3) of ADI about 33 (30, 35). The prevalence rate of T2DM was 16.41% (857/5 223). After adjusting for covariates, multivariate logistic regression showed that PDI was negatively associated with T2DM. Compared with the low-level group, the OR (95% CI) for T2DM in the high-level group was 0.83 (0.69-0.99). ADI was positively associated with T2DM, and compared with the low-level group, the OR (95% CI) for T2DM in the high-level group was 1.28 (1.06-1.55). For every one-point increase in PDI and ADI, the risk of T2DM decreased by 2% and increased by 3%, respectively, with the OR (95% CI) of 0.98 (0.96-1.00) and 1.03 (1.01-1.06), respectively. Conclusion:In Chinese older adults ≥65 years in 18 longevity areas, higher adherence to the plant-based behavior may be negatively associated with the risk of T2DM, while higher adherence to the animal-based behavior may be positively associated with the risk of T2DM.

Objective:To explore the applicability of endoscopic retrograde appendicitis therapy (ERAT) and methods of aeromedical assessment of military flying personnel with appendicitis.Methods:The diagnosis, ERAT process and aeromedical assessment of 2 military flying personnel with appendicitis were analyzed while the related literature was reviewed.Results:Two military flying personnel diagnosed with appendicitis underwent ERAT after appendiceal perforation or intra-abdominal infection was ruled out. Abdominal pain was resolved within one day of ERAT while inflammatory markers were normalized within one week. Both patients returned to flight duties 1-2 weeks after the procedure. During a follow-up of over one year, both remained excellent in flight performance.Conclusions:For military flying personnel with uncomplicated appendicitis, ERAT is a safe and effective treatment. Patients can return to flight duties within 1-2 weeks of resolution of postoperative abdominal pain symptoms. Compared with traditional appendectomy, ERAT can shorten the grounding time for military flying personnel.

Objective To explore a nomogram of intratumor and peritumor radiomics based on enhanced CT venous phase to pre-operatively predict the pathological grade of poorly differentiated esophageal squamous cell carcinoma(ESCC).Methods A retro-spective selection was made of 266 ESCC patients confirmed by pathology(76 cases of poorly differentiated;190 cases of non-poorly differentiated),and all patients were randomly divided into training set(n=186),validation set(n=80),and full data set(n=266).Tumors were segmented on the enhanced CT venous phase to create three-dimensional region of interest(ROI)of intratumor,peritu-mor 0.3 cm,and intratumor+peritumor 0.3 cm.A total of 2 553 radiomics features were extracted.After feature dimensionality reduc-tion,XGboost machine learning algorithm was utilized to rank the top fifteen features.Stepwise forward multiple logistic regression was employed to identify the most significant features.The radiomics scores of the intratumor,peritumor 0.3 cm,and intratumor+peritu-mor 0.3 cm were calculated.The diagnostic efficacy of the model was evaluated using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA).Results The nomogram constructed based on radiomics scores of intratumor,peritumor 0.3 cm,intratumor+peritumor 0.3 cm in the training set for preoperative prediction of poorly differentiated ESCC had an AUC of 0.899[95％confidence interval(CI)0.846-0.938],and it was well validated in the vali-dation set(AUC 0.869,95％CI 0.775-0.934)and the full data set(AUC 0.889,95％CI 0.845-0.924).Additionally,calibration curves and DCA indicated that the nomogram achieved good calibration ability in the three cohorts and offered greater clinical net benefit.Conclusion The nomogram based on enhanced CT venous phase intratumor and peritumor radiomics achieves a high and stable diagnostic efficacy for preoperatively predicting poorly differentiated ESCC,which may help with individualized surgical selec-tion and management before surgery.

Guidelines for Digital Ancient Books of TCM Indexing(T/CIATCM 119-2024)is based on the theoretical knowledge,disciplinary methods,and practical applications of TCM classical cataloging.Taking digital ancient books of TCM as the object,it systematically reveals the content of TCM knowledge,which is an essential indexing processing standard for building an intelligent retrieval system for TCM ancient books,and can provide support for the deep development and innovative utilization of TCM knowledge.It can not only promote the co-construction and sharing of ancient book resources in the TCM industry,but also promote the standardization construction and application of TCM information.This standard specifies the principles,methods,and examples of free indexing of digital ancient books of TCM based on their original content.It is applicable to the indexing and processing of digital ancient books of TCM for TCM professional libraries and related institutions,and to the data processing and construction of various types of TCM ancient book databases.