Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

This review summarizes recent advances in neoadjuvant immunotherapy for advanced gastric cancer.Through literature search in PubMed,Web of Science,and CNKI databases from 2020 to 2023,we systematically analyzed the mechanisms,clinical applications,and bio-marker research.Programmed death-1(PD-1)inhibitors combined with chemotherapy significantly improve patient outcomes,while mi-crosatellite instability(MSI),programmed death-ligand 1(PD-L1)expression,and tumor mutational burden(TMB)have been identified as important predictive biomarkers.Multi-omics analysis shows great potential in identifying optimal responders,with pyroptosis-related gene scoring system(PRS)positively correlating with anti-tumor immune infiltration.Metabolic reprogramming and epigenetic regulation in the tumor microenvironment play key roles in immune evasion,while emerging targets such as Claudin 18.2 and combination targeting strategies further enhance therapeutic efficacy.Despite significant progress,precise patient selection and overcoming resistance mechan-isms remain major challenges.Future research should focus on biomarker validation,personalized treatment strategy development,tumor microenvironment dynamic analysis,and novel combination therapy exploration to improve clinical outcomes.

ObjectiveBased on literature data mining， this study explores the modeling elements of diarrhea-predominant irritable bowel syndrome （IBS-D） animal models in China and abroad， providing references and suggestions for improving modeling methods and evaluation indicators. MethodsRelevant literature on IBS-D animal experiments from 2014 to 2024 was retrieved through computer searches in databases such as China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， Chinese Medical Journals Full-text Database， and PubMed. Information on experimental animal species， gender， body weight， modeling methods， modeling periods， intervention controls， modeling standards， and detection indicators was organized. Microsoft Excel 2021 software was used to establish a database and perform statistical analysis to examine the characteristics of IBS-D animal models. ResultsA total of 398 articles that met the inclusion criteria were reviewed. The IBS-D animal models were predominantly established using SD rats， Wistar rats， and C57BL/6 mice. Male animals were more commonly used， with rats typically aged 6-8 weeks and mice aged 4-6 weeks. In terms of interventions， piverium bromide was the main Western medicine， Tongxieyaofang was the primary Chinese medicine， and electroacupuncture was the primary acupuncture method. Among the modeling methods， the multi-factor combined composite modeling approach was the most common. Modeling periods were mainly concentrated between 1-14 days and 15-30 days. The success criteria for modeling were mainly evaluated based on the animal's general condition， fecal appearance， visceral sensitivity， gastrointestinal motility， behavior， and pathology. Detection indicators included apparent indexes， pathological markers， biochemical indicators， oxidative stress， brain-gut peptides， neurotransmitters， inflammatory factors， immune function， intestinal permeability， autophagy， apoptosis， proteins related to relevant signaling pathways， intestinal microbiota and its metabolites， etc. ConclusionThere are various methods for establishing IBS-D animal models， but no unified and universally accepted method has been established. The operation of the same modeling methods and the evaluation standards of the models vary across studies. Based on the results of data mining， the authors suggest that the multi-factor combined composite modeling approach most closely reflects the pathophysiological processes of IBS-D， better simulating the complex clinical symptoms of IBS-D patients， such as abdominal pain and diarrhea， and has a high degree of clinical relevance. This method is relatively recommended. While animal models in general align with Western medicine standards， models incorporating traditional Chinese medicine （TCM） syndromes are relatively few. Therefore， one of the future directions for research is to establish IBS-D animal models that meet the combined clinical disease and syndrome requirements of both Western and Chinese medicine.

Objective:To explore the deubiquitination modification of the deubiquitinase BRCC3 in rats with neuropathic pain (NPP) treated with meridian tuina of Zhuang medicine and its analgesic molecular mechanism.Methods:Rats were divided into normal group, sham-operation group, model group, sham-tuina group, and meridian tuina of Zhuang medicine group using a random number table method, with 9 rats in each group. Except for the normal and sham operation groups, spinal nerve ligation models were prepared in all other groups. On the first day after surgery, intervention was carried out on the meridian tuina of Zhuang medicine and sham-tuina groups for 14 days, while the other three groups were not intervened; the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) of each group of rats were measured at 0 days before operation, 1, 7, and 14 days after operation. Western blot was used to detect the expressions of BRCC3 and NLRP3 proteins in spinal cord tissue, and ELISA was used to detect the level of IL-1β in serum.Results:On postoperative 7 and 14 d, compared with the model group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLPR3 and BRCC3 expression in spinal cord tissue, and a decrease in serum IL-1β levels ( P<0.05). Compared with the sham-tuina group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLRP3 protein expression in spinal cord tissue, and a decrease in IL-1β levels in serum ( P<0.05). Conclusion:Meridian tuina of Zhuang medicine can alleviate pain sensitivity in SNL model rats, and its mechanism is related to the inhibition of the expression of deubiquitinase BRCC3 by meridian massage of Zhuang medicine, which increases the ubiquitination level of NLRP3 and hinders its activation, thereby blocking the immune inflammatory response mediated by inflammatory factors.

Objective:To observe the clinical efficacy of azithromycin for the treatment of Mycoplasma pneumoniae pneumonia(MPP)with gene mutations at site A2063G of 23S rRNA in children.Methods:Data were retrospectively collected for 242 children diagnosed with MPP at Sichuan Provincial Maternity and Child Health Care Hospital from January to December 2023,in whom MPP was detected using targeted next-generation sequencing(tNGS).According to the presence or absence of mutations,the children were classified into mutation group(88 cases)and non-mutation group(154 cases).Results:Gene mutations at site A2063G of 23S rRNA were detected in 88 patients.The chest X-rays of both groups showed more lesions in the right lung than in the left lung.Both groups were treated with azithromycin and compared for differences in age,sex,duration of fever,C-reactive protein level,time to improvement of chest X-rays,days of medication,and response rate,with no significant differences found in the above indicators(P>0.05).However,the duration of respiratory symptoms was significantly longer in the mutation group than in the non-mutation group[(11.51±3.31)d vs.(10.06±3.63)d,P<0.05].Conclusion:Azithromycin is effective in treating MPP with gene mutations at site A2063G of 23S rRNA.

Objective To explore the efficacy and safety of side-to-side anastomosis(SS)and end-to-side anastomosis(ES)of the ileocolon in laparoscopic right hemicolectomy of colon cancer,so as to provide evidence-based evidence for surgical selection.Methods PubMed,Embase,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,VIP database,Chinese BioMedical Literature database were searched from inception to November 2024 to collect relevant clinical studies of SS versus ES.The Newcastle-Ottawa Scale(NOS)was used to evaluate the literature quality of retrospective studies,and the Cochrane system was used to evaluate the literature quality of randomized controlled trials(RCT).Rev Man 5.3 software was used for Meta-analysis,sensitivity analysis,and publication bias analysis.Results 9 retrospective studies and 4 RCTs with a total of 2 632 patients were included.The Meta-analysis results of the retrospective study show that:Compared with SS,ES has a shorter tolerance time for liquid diet(MD=-0.20,95%CI:-0.40～0.00,P<0.05),fewer daily episodes of diarrhea(MD=-1.06,95%CI:-1.79～0.23,P<0.05),but a higher pain score at 12 hours post-surgery(MD=0.95,95%CI:0.50～1.40,P<0.05).Comparison of the overall complication rates of the two anastomosis methods showed no statistically significant difference((OR)=1.05,95%CI:0.22～5.14,P>0.05).Sensitivity analysis of the retrospective study shows:the incidence of ES bowel obstruction was higher than that of SS,with a statistically significant difference((OR)=2.18,95%CI:1.15～4.14,P<0.05);The sensitivity analysis of the RCT shows:the overall incidence of complications at the anastomotic site of SS was significantly higher than that of ES,with a statistically significant difference((OR)=5.26,95%CI:1.91～14.48,P<0.05),and the results of other outcome indicators did not show reversal.The analysis of publication bias risk showed no significant publication bias.Conclusion Ileocolonic ES has a slight advantage over SS in laparoscopic right hemicolectomy of colon cancer,both anastomoses are safe and effective,and the surgeon can choose the appropriate anastomosis technique according to the patient's specific situation,in order to improve the postoperative recovery.

Objective:To preliminarily establish a valuable threshold for the college students’ psychological Suzhi questionnaire simplified version (CSPSz-SV) by means of the latent profile analysis and the receiver operating characteristic(ROC) curve.Methods:The CSPSz-SV was applied to investigate 1 870 college freshmen from undergraduate colleges. The identification threshold value of the CSPSz-SV was identified by combining latent profile analysis (LPA) and the ROC curve.Both Mplus 8.3 and R 4.3.1 software were used for the data analysis.Results:Based on LPA results, the college freshmen were divided into three categories according to the levels of psychological Suzhi: the low psychological Suzhi group, the medium psychological Suzhi group, and the high psychological Suzhi group.Following the LPA, the ROC analysis was conducted to obtain the optimal critical value (91) of the psychological Suzhi level for college freshmen (Youden's index was 0.934, sensitivity was 0.979, specificity was 0.955, positive predictive value was 0.855, negative predictive value was 0.994, accuracy was 0.960, and AUC was 0.991, respectively). College freshmen were divided into the abnormal psychological Suzhi group and the normal psychological Suzhi group in accordance with this critical value, and the difference between the two groups was statistically significant (Cohen's d=1.74-2.18, P<0.001). Conclusion:The threshold value established and obtained in this study can be reviewed as a reference for evaluating the psychological Suzhi level of college freshmen.

Objective To explore the efficacy and safety of side-to-side anastomosis(SS)and end-to-side anastomosis(ES)of the ileocolon in laparoscopic right hemicolectomy of colon cancer,so as to provide evidence-based evidence for surgical selection.Methods PubMed,Embase,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,VIP database,Chinese BioMedical Literature database were searched from inception to November 2024 to collect relevant clinical studies of SS versus ES.The Newcastle-Ottawa Scale(NOS)was used to evaluate the literature quality of retrospective studies,and the Cochrane system was used to evaluate the literature quality of randomized controlled trials(RCT).Rev Man 5.3 software was used for Meta-analysis,sensitivity analysis,and publication bias analysis.Results 9 retrospective studies and 4 RCTs with a total of 2 632 patients were included.The Meta-analysis results of the retrospective study show that:Compared with SS,ES has a shorter tolerance time for liquid diet(MD=-0.20,95%CI:-0.40～0.00,P<0.05),fewer daily episodes of diarrhea(MD=-1.06,95%CI:-1.79～0.23,P<0.05),but a higher pain score at 12 hours post-surgery(MD=0.95,95%CI:0.50～1.40,P<0.05).Comparison of the overall complication rates of the two anastomosis methods showed no statistically significant difference((OR)=1.05,95%CI:0.22～5.14,P>0.05).Sensitivity analysis of the retrospective study shows:the incidence of ES bowel obstruction was higher than that of SS,with a statistically significant difference((OR)=2.18,95%CI:1.15～4.14,P<0.05);The sensitivity analysis of the RCT shows:the overall incidence of complications at the anastomotic site of SS was significantly higher than that of ES,with a statistically significant difference((OR)=5.26,95%CI:1.91～14.48,P<0.05),and the results of other outcome indicators did not show reversal.The analysis of publication bias risk showed no significant publication bias.Conclusion Ileocolonic ES has a slight advantage over SS in laparoscopic right hemicolectomy of colon cancer,both anastomoses are safe and effective,and the surgeon can choose the appropriate anastomosis technique according to the patient's specific situation,in order to improve the postoperative recovery.

Objective:To preliminarily establish a valuable threshold for the college students’ psychological Suzhi questionnaire simplified version (CSPSz-SV) by means of the latent profile analysis and the receiver operating characteristic(ROC) curve.Methods:The CSPSz-SV was applied to investigate 1 870 college freshmen from undergraduate colleges. The identification threshold value of the CSPSz-SV was identified by combining latent profile analysis (LPA) and the ROC curve.Both Mplus 8.3 and R 4.3.1 software were used for the data analysis.Results:Based on LPA results, the college freshmen were divided into three categories according to the levels of psychological Suzhi: the low psychological Suzhi group, the medium psychological Suzhi group, and the high psychological Suzhi group.Following the LPA, the ROC analysis was conducted to obtain the optimal critical value (91) of the psychological Suzhi level for college freshmen (Youden's index was 0.934, sensitivity was 0.979, specificity was 0.955, positive predictive value was 0.855, negative predictive value was 0.994, accuracy was 0.960, and AUC was 0.991, respectively). College freshmen were divided into the abnormal psychological Suzhi group and the normal psychological Suzhi group in accordance with this critical value, and the difference between the two groups was statistically significant (Cohen's d=1.74-2.18, P<0.001). Conclusion:The threshold value established and obtained in this study can be reviewed as a reference for evaluating the psychological Suzhi level of college freshmen.