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.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Objective:Based on the activities of Helicobacter pylori ( HP) screening in Jiangsu Province in 2024, to evaluate the overall management ability in HP screening, testing, treatment and follow-up in primary medical facilities. Methods:From May 15 to October 18, 2024, the data of HP screening and treatment were retrospectively collected from 79 township health centers, community hospitals, and community health service centers in Jiangsu Province. The rates of screening completion, urea breath test (UBT) completion, treatment rate, UBT follow-up completion, and HP eradication were analyzed. Chi-square test was used for statistical analysis. Results:The completion rate of HP screening was 94.45% (15 489/16 400). There were 6 604 cases (42.64%) with serum HP antibody positive among the 15 489 individuals who completed screening. The positive rate of serum HP antibody in males was higher than that in females (44.77%, 2 643/5 904 vs. 41.32%, 3 961/9 585), and the difference was statistically significant ( χ2=17.69, P<0.001). The positive rates of serum HP antibody in screened individuals aged 18 to 19, 20 to 39, 40 to 59, and 60 to 75 years old were 22.38% (32/143), 36.12% (1 168/3 234), 45.01% (3 240/7 199), and 44.05% (2 164/4 913), respectively, and the difference was statistically significant( χ2=100.73, P<0.001). Among the 6 604 HP antibody-positive individuals, 4 381 cases completed UBT, with a UBT completion rate of 66.34% (4 381/6 604). There were 3 197 individuals with both HP serum antibody and UBT positive, the consistency rate of the 2 tests was 72.97% (3 197/4 381). Totally 2 737 cases received treatment, with a treatment completion rate of 85.61% (2 737/3 197); 2 327 individuals underwent UBT follow-up, with a follow-up completion rate of 85.02% (2 327/2 737). During follow-up, the result of UBT was negative in 1 982 individuals, and the HP eradication rate was 85.17% (1 982/2 327). Conclusions:There are deficiencies in the completion rate of HP screening, testing, treatment, and follow-up in primary hospitals, especially in the completion rate of UBT, which may be related to cognitive insufficiency for HP in residents. It is necessary to strengthen the training of physicians′ abilities in primary hospitals, optimize the allocation of drug resources, enhance health education, and increase residents′ participation and compliance.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Recent studies have identified a missense mutation in the β1-receptor (ADRB1-A187V) that exerts a pronounced impact on human sleep, with a noted decrease in protein abundance in vivo. The administration of β-blockers is frequently associated with sleep disturbances in clinical settings. In this study, we assessed the influence of various β-blockers on sleep within mouse models. Our findings indicated that β-blockers could induce varying degrees of arousal, sleep disruption, and a decrease in REMS (rapid eye movement sleep). We examined the dose-dependent effects of metoprolol and nebivolol on both sleep and cardiac functionality in both wild-type and Adrb1-A187V mutant mice. Our data suggested that, in contrast to cardiac effects, higher doses of metoprolol are required to have noted impact on sleep. No genotype effect was observed with metoprolol in terms of sleep or cardiac function. In contrast, the mutant mice demonstrated increased sensitivity to nebivolol, which exacerbated sleep fragmentation and impeded the onset of REMS. This study is expected to provide some reference for minimizing the occurrence of sleep disorders and reducing the adverse reactions of drugs to the greatest extent.

Temporomandibular joint (TMJ) subluxation is a condition among temporomandibular disorders. It is common in clinical practice, but it is often underrecognized, and easily confused with conditions such as TMJ displacement, TMJ dislocation and other diseases. Therefore, it is necessary to discuss the diagnosis and treatment of TMJ subluxation through comprehensive analysis of its definition, pathogenesis and clinical manifestations.

Objective:Exploring the changes in the expression of transient receptor potential vanilloid 1 (TRPV1) in the peripheral and central nervous system in rats temporomandibular joint osteoarthritis (TMJOA) and its relationship with TMJOA pain .Methods:From February 2024 to April 2025, 48 healthy male Sprague Dawley rats were randomly divided into a control group and an experimental group, with 24 rats in each group. The modeling periods for both groups were 2, 4, and 6 weeks, with 8 rats per group at each time point. After bilateral injection of monosodium iodoacetate (MIA) into the temporomandibular joint (TMJ) cavity to establish a TMJOA model, the TMJ condyle, trigeminal ganglion (TG), trigeminal nucleus caudate (TNC), and hippocampal tissue were collected. Pain threshold detector von Frey silk was used to evaluate the head withdrawal threshold (HWT) of rats, and HE staining and micro-CT scanning were used to observe the histological changes of TMJ. Immunohistochemical staining was used to detect the expression of TRPV1 in TG and hippocampal tissues, as well as the expression of glial fibrillar acidic protein (GFAP) in TNC.Results:On the first day after modeling, the HWT of rats significantly decreased and then gradually increased. From day 7 to day 14, HWT decreased again, and after day 14, HWT gradually increased. Statistically significant differences were observed between the experimental group and the control group at each time point ( P<0.001). HE staining and micro-CT revealed that in the second week after modeling, the arrangement of condylar bone trabeculae was disordered, the trabeculae became thinner, the bone marrow cavity became larger, and then the trabeculae became thicker and the bone marrow cavity became smaller. The number of TRPV1 positive cells in TG of TMJOA rats reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001), with no statistically significant difference in the control group ( P=0.941). The number of GFAP positive cells in TNCs of TMJOA rats significantly increased, reaching its peak in the second week of modeling and gradually decreasing in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.720). The number of TRPV1 positive cells in the hippocampus of TMJOA rats significantly increased. The number of TRPV1 positive cells reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.776). Conclusions:In the MIA induced rat TMJOA model, the expression of TRPV1 in TG and hippocampal tissue, as well as the expression of GFAP in TNC, were upregulated, which may be involved in the occurrence and development of TMJOA pain and related to the development of TMJOA lesions.

Neuropathic pain(NP)is a type of chronic pain caused by damage or disease of the nervous system.It is mainly characterized by spontaneous pain,hyperalgesia,and allodynia,which seriously af-fect the quality of life of patients.The pathogenesis of NP is complex,involving abnormal regulation such as peripheral sensitization,central sensitization,ion channel changes,and glial cell activation.In recent years,the role of m6A in NP has attracted extensive attention.However,the research on the role of m6A modification in different diseases and pain models is still limited.Therefore,it is particularly important to clarify the role of m6A modification in different diseases and pain models.This article reviews the re-search progress on the role and mechanism of m6A methylation modification in the pathogenesis of NP in recent years,especially the role mechanism of the five classical m6A modification factors,METTL3,METTL14,FTO,ALKBH5 and YTHDF1,in mediating the formation of NP in different diseases and pain models,with the expectation of providing new insights and ideas for the drug development and pre-vention of NP from the perspective of m6A modification.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.