Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.

OBJECTIVE To construct a preoperative medication reconciliation model assisted by a localized large language model （LLM） for gastric cancer and evaluate its clinical efficacy. METHODS A total of 249 gastric cancer patients with a history of continuous medication before admission in the Gastric Surgery Department of Jiangsu Cancer Hospital were retrospectively enrolled. Patients were divided into training set （154 cases） and validation set （95 cases） based on the order of time. Based on guidelines， drug package inserts， and other evidence， a standardized medication reconcili ation process and a structured knowledge base were constructed. DeepSeek-V3 LLM was deployed privately in the hospital， combined with retrieval-augmented generation technology， to achieve automated integration of medication information， risk screening， and generation of personalized recommendations. The quality of LLM-generated recommendations was evaluated using automatic metrics （BERT Score and ROUGE-1， 2， L） and manual scoring [seven-dimensional index （7DI） ] . Spearman correlation analysis was performed to explore the correlation between automatic scores and manual scores. Cronbach’s α coefficient was used to test the internal consistency of manual scoring results. The time consumed by manual and LLM-assisted medication reconciliation was compared across tasks of different difficulty levels （simple， moderate， and high）. RESULTS A structured knowledge base covering 8 major drug categories was finally established， covering common and high-risk preoperative medication scenarios and providing structured retrieval support for the LLM. For automatic evaluation， the precision， recall， and F1-score of BERT Score were 0.783±0.033， 0.811±0.038， and 0.796±0.028， respectively. The F1-scores of ROUGE-1， ROUGE-2 and ROUGE-L were 0.566±0.067， 0.338±0.076 and 0.468±0.082， respectively. The 7DI scores from three manual raters ranged from 32.06 to 33.45. The F1-score of automatic scoring was significantly positively correlated with the 7DI score of manual scoring （maximum coefficient of determination＝0.611， P ＜0.001）， and the internal consistency of manual scoring was good （Cronbach’s α ＝ 0.876）. In terms of efficiency， LLM-assisted medication reconciliation reduced time consumption by more than 90% compared with manual reconciliation in the simple， moderate， and high-difficulty groups （ P ＜0.001）. CONCLUSIONS The medication reconciliation model constructed based on a localized LLM and structured knowledge base shows high accuracy， consistency， and clinical applicability in complex preoperative medication scenarios for gastric cancer. It can improve the efficiency of medication reconciliation and reduce potential medication risks.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective To explore the behavioral characteristics of using cognitive reappraisal(CR)and expressive suppression(ES)in high trait anxiety individuals under both explicit and implicit conditions.Methods A total of 57 non-psychology undergraduates and postgraduates were recruited in a military medical university from June to July in 2023.All the participants were surveyed with Trait Form of Spielberger's State-Trait Anxiety Inventory(STAI-T)and Emotion Regulation Questionnaire(ERQ)to investigate their level of anxiety and usage habits of CR and ES strategies.According to the STAI-T results,they were divided to a high trait anxiety(HTA)group(n=28)and a low trait anxiety(LTA)group(n=29).Then the implicit and explicit emotion regulation(ER)tasks were used to analyze and compare 2 strategies on improving negative emotional pleasure and arousal,and the differences in difficulty and success of using CR and ES under the explicit condition.Results ① Both the HTA and LTA individuals showed a higher use of CR and less use of ES[t(27)=3.94,P<0.001;t(28)=11.33,P<0.001],while the HTA individuals used more ES[t(55)=3.02,P<0.01]and less CR than the LTA individuals[t(55)=-2.20,P=0.02].②Compared with implicit neutral priming,both implicit CR(Pleasure:2.56±0.11 vs 2.73±0.12,P<0.01;Arousal:6.68±0.18 vs 6.51±0.20,P<0.05)and implicit ES priming(Pleasure:2.56±0.11 vs 2.86±0.11,P<0.001;Arousal:6.68±0.18 vs 6.30±0.20,P<0.001)improved the negative emotional experiences of both HTA and LTA groups,and ES showed better effect(Pleasure:P<0.001;Arousal:P<0.001).③ Explicit CR(Pleasure:2.92±0.12 vs 5.09±0.09,P<0.001;Arousal:6.43±0.20 vs 4.33±0.21,P<0.001)and explicit ES(Pleasure:2.92±0.12 vs 4.34±0.09,P<0.001;Arousal:6.43±0.20 vs 4.22±0.22,P<0.001)ameliorated the negative feelings in the HTA and LTA individuals,and the effect of explicit CR on improving pleasure was superior than that of explicit ES(P<0.001).For the HTA individuals,it is more difficult to implement CR and ES[CR:t(55)=2.16,P=0.02;ES:t(55)=2.92,P<0.01],and ES was less successful in emotion regulation when compared with the LTA individuals[t(55)=-1.88,P=0.03];the difficulty of using ES was significantly higher than that of CR[4.00±1.81 vs 5.00±1.80,t(27)=-2.78,P<0.01],and the success rate was also lower[7.04±1.00 vs 6.64±1.13,t(27)=2.09,P=0.02].④ Comparing the effects of emotion regulation under implicit and explicit conditions,it was presented that explicit CR and ES were better than implicit CR and ES for both HTA and LTA individuals(Pleasure:explicit CR vs implicit CR:5.09±0.09 vs 2.73±0.12,P<0.001;explicit ES vs implicit ES:4.34±0.09 vs 2.86±0.11,P<0.001;Arousal:explicit CR vs implicit CR:4.33±0.21 vs 6.51±0.20,P<0.001;explicit ES vs implicit ES:4.22±0.22 vs 6.30±0.20,P<0.001).Conclusion In terms of usage habits of ER strategies,HTA individuals tend to use ES more and CR less than LTA individuals.Under the implicit/explicit conditions,HTA individuals can both employ CR and ES to improve negative emotional experience,and the effect of explicit ER is significantly better than implicit condition.

Objective To establish a rapid immunological detection method for MPT64 protein based on red microspheres and select highly-sensitive and highly-specific antibody pairs.Methods A His-tagged prokaryotic expression vector was constructed for expression of MPT64 protein that was used to immunize New Zealand white rabbits after purification and validation.Peripheral blood mononuclear cells(PBMCs)were isolated from the rabbits,and antigen-specific B cells expressing antibodies were sorted using single B-cell flow cytometry.mRNA in B cells was reverse-transcribed into cDNA,and paired antibody heavy-and light-chain sequences were amplified via nested PCR.Expression vectors were constructed,and recombinant antibodies were produced in Expi293F cells.Fluorescent immunochromatography was employed to screen for matched antibody pairs.The selected antibodies were used to establish a rapid detection method based on red microsphere immunochromatography.Results Ten high-affinity monoclonal antibodies against MPT64 were generated.Two antibody pairs were selected for MPT64 immunodetection that reached a sensitivity of 0.0125 ng/mL.Conclusion High-affinity rabbit monoclonal antibodies against MPT64 are obtained via single B-cell technology,and a rapid red microspheres-based immunodetection method is established,enabling highly sensitive detection of Mycobacterium tuberculosis MPT64 protein.

Objective To investigate the impact of various health education intervention strategies on the proper use of personal respiratory protective equipment (RPE) among workers exposed to dust. Methods Dust-exposed workers were recruited from 60 selected enterprises in Guangdong Province using cluster random sampling method. They were randomly allocated to the control, low-intensity intervention, and high-intensity intervention groups, with 358, 346, and 371 workers in each group, respectively. Workers in the control group received no designed intervention. Workers in the low-intensity intervention group received traditional plus mobile health education on the proper use of RPE. Workers in the high-intensity intervention group received all components of the low-intensity intervention, supplemented with peer education. The intervention lasted for six months. RPE usage was compared among the three groups of workers before and after the intervention. Results Workers in the control, low-intensity intervention, and high-intensity intervention groups showed higher rates of both RPE wearing and correct RPE wearing after the intervention than before it within their respective groups (RPE wearing rate: 94.1% vs 99.2%, 95.7% vs 100.0%, 94.6% vs 100.0%, all P<0.01; correct RPE wearing rate: 66.8% vs 91.1%, 67.3% vs 95.7%, 66.6% vs 96.5%, all P<0.01). Post-intervention correct RPE wearing rates were highest in the high-intensity intervention group, followed by the low-intensity intervention group, and the control group, with the percentage of 96.50%, 95.66% and 91.06%, respectively (P<0.01). Binary logistic regression analysis result showed that different intervention strategies affected the correct use of personal RPE among dust-exposed workers after adjusting for gender, age, and other confounding factors (P<0.05). Compared with the control group, the rates of correct RPE use increased in the low-intensity intervention group and the high-intensity intervention group (odd ratio was 2.14 and 3.01; 95% confidence interval was 1.12 - 4.10 and 1.53 - 5.91, respectively). Conclusion The implementation of traditional plus mobile health education interventions on the proper use of RPE can promote correct RPE utilization among dust-exposed workers, and integrating peer education further enhances the intervention effectiveness.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.