The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

Objective To establish a stable in vitro model of CD8+T cell exhaustion.Methods CD8+T cells were isolated and purified from the spleens of ovalbumin-specific CD8+T cell receptor(OT-I)transgenic mice and subjected to chronic antigen stimulation to induce exhaustion in vitro.Flow cytometry was employed to evaluate the expressions of exhaustion markers,secretion of effector cytokines,and transcription factor profiles in CD8+T cells.Exhausted and effector(non-exhausted)CD8+T cells were co-cultured with tumor cells before tumor cell viability was measured to assess the cytotoxic potential of CD8+T cells.Additionally,N-acetyl-L-cysteine(N-AC)was used as a positive control during exhaustion induction to validate the model.Results Chronic stimulation resulted in a significant upregulation of inhibitory receptors,including programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(TIM-3),T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motifdomain(TIGIT),and lymphocyte activation gene 3(LAG-3).Concurrently,the secretion of key effector cytokines such as tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)was markedly reduced.Exhausted CD8+T cells exhibited diminished cytotoxicity against tumor cells compared to effector CD8+T cells.Notably,treatment with N-AC effectively restored the function of exhausted CD8+T cells and enhanced their anti-tumor activity.Conclusion This study has established an effective in vitro model for CD8+T cell exhaustion.The use of N-AC demonstrates its potential to restore functionality in exhausted CD8+T cells,underscoring the reliability and utility of this model for investigating the anti-tumor potential of exhausted T cells.

Objective:To investigate the effects of pulsed electric field (PEF) combined with gemcitabine (GEM) on the viability and stemness of HCCC-9810 cholangiocarcinoma stem cells.Methods:HCCC-9810 cholangiocarcinoma stem cells were established in serum-free, cytokine-rich medium and divided into four groups: the control group, GEM group, PEF group, and the pulsed electric field combined with gemcitabine (PEF+ GEM) group. Cell proliferation was detected using the Cell Counting Kit-8 (CCK8) assay. Cell viability and apoptosis rate were measured by flow cytometry. Cell invasion ability was assessed using the Transwell assay. The expression of stemness marker proteins CD133 and Octamer-binding transcription factor 4 (OCT4), as well as the expression of β-catenin, was detected by Western blotting.Results:Regarding cell viability, the GEM, PEF, and PEF+ GEM groups showed significantly lower cell viability and higher apoptosis rate than the control group at 24 h, 48 h, and 72 h (all P<0.05). At 48 h and 72 h, the PEF+ GEM group showed significantly lower cell viability (7.2%±0.3% and 5.9%±0.8%, respectively) than the GEM group (50.7%±0.6% and 31.0%±1.2%, respectively) and the PEF group (12.2%±0.2% and 12.8%±0.2%, respectively) (all P<0.05). Regarding stemness inhibition, the PEF+ GEM groups showed significantly lower expression levels of CD133 and OCT4 at 24 h, 48 h, and 72 h compared with the control group (all P<0.05). Notably, at 48 h, the PEF+ GEM group showed a significantly lower expression level of the OCT4 (0.61±0.02) than the GEM group (0.87±0.08) and the PEF group (1.00±0.10) ( P<0.01). Furthermore, at 24 h and 48 h, the GEM, PEF, and PEF+ GEM groups showed significantly lower expression levels of β-catenin compared with the control group (all P<0.05). Conclusion:Pulsed electric field combined with gemcitabine therapy demonstrated more effective anti-proliferation and cancer stemness inhibition effects on HCCC-9810 cholangiocarcinoma stem cells compared with either monotherapy.

The wide application of assisted reproductive technology (ART) has brought the hope of fertility to infertile couples worldwide. However, with the gradual popularization of ART, the long-term health status of ART children has attracted extensive attention from society. Adolescence is a critical developmental period for individuals to transition from childhood to adulthood, with significant physical and psychological changes, so the health status of ART offspring during this period has a profound impact on their overall future health. This article reviews the existing studies, focusing on the effects of ART on multiple aspects of adolescent health, especially growth and development, cardiovascular health, endocrine function, fertility, cancer risk, atopic diseases, mental health, epigenetic changes and other aspects. The possible mechanisms leading to these health problems, including genetic factors, environmental exposures, and the long-term effects of early life interventions, were explored. Future research should continue to explore the long-term effects of ART on the health of offspring and further clarify the mechanisms of these effects, so as to provide a scientific basis for the development of effective prevention and intervention measures.

Objective:To investigate the influence of inner cell mass and trophectoderm cytoplasmic strings during blastocyst expan-sion on embryonic development and pregnancy outcome.Methods:A retrospective cohort analysis was performed for the clinical data of patients who received pre-implantation genetic testing for aneuploidy(PGT-A)and underwent single blastocyst transplantation in our hospital from June 2019 to December 2021.A total of 530 patients were enrolled,and genetic testing was performed for 2132 blasto-cysts.According to the presence or absence of cytoplasmic strings during blastocyst expansion,the blastocysts were divided into cyto-plasmic strings(+)group with 534 blastocysts and cytoplasmic strings(-)group with 1598 blastocysts,and quality and PGT-A results were compared between the two groups.After the transfer of euploid blastocysts,pregnancy outcome was compared between the 115 blastocysts with cytoplasmic strings and the 415 blastocysts without cytoplasmic strings.Results:The rates of cytoplasmic strings(+)in the high-,average-,and low-quality blastocyst groups were 30.19%,24.62%,and 12.63%,respectively.The correlation analysis showed a correlation coefficient of-0.115(P<0.001)between embryo quality and the rate of cytoplasmic strings(+).There was no sig-nificant difference in euploidy rate between the two groups(45.3%vs.44.6%).There were no significant differences between the euploid blastocysts with cytoplasmic strings and those without cytoplasmic strings in implantation rate(72.17%vs.66.02%,P=0.213),miscarriage rate(14.46%vs.12.77%,P=0.691),and live birth rate(61.74%vs.57.59%,P=0.424).Conclusion:The presence of cyto-plasmic strings is associated with the morphological quality of blas-tocysts,while it has no impact on embryo ploidy or clinical outcome after euploid embryo transfer.Further research is needed to confirm the impact of cytoplasmic strings on embryonic development.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

The wide application of assisted reproductive technology (ART) has brought the hope of fertility to infertile couples worldwide. However, with the gradual popularization of ART, the long-term health status of ART children has attracted extensive attention from society. Adolescence is a critical developmental period for individuals to transition from childhood to adulthood, with significant physical and psychological changes, so the health status of ART offspring during this period has a profound impact on their overall future health. This article reviews the existing studies, focusing on the effects of ART on multiple aspects of adolescent health, especially growth and development, cardiovascular health, endocrine function, fertility, cancer risk, atopic diseases, mental health, epigenetic changes and other aspects. The possible mechanisms leading to these health problems, including genetic factors, environmental exposures, and the long-term effects of early life interventions, were explored. Future research should continue to explore the long-term effects of ART on the health of offspring and further clarify the mechanisms of these effects, so as to provide a scientific basis for the development of effective prevention and intervention measures.

BackgroundIt has been shown that academic procrastination， cognitive emotion regulation strategies， anxiety and mobile phone dependence are closely related， but the detailed mechanism by which academic procrastination contributes to mobile phone dependence remains largely unclear and mediation analysis is currently lacking. ObjectiveTo explore the mediation role of cognitive emotion regulation strategies and anxiety in the relationship between academic procrastination and mobile phone dependence among college students， so as to provide references for the prevention and intervention of college students' mobile phone dependence. MethodsIn March 2023， 474 students from Xinjiang Normal University were selected by random sampling technique， and Mobile Phone Addiction Index （MPAI）， Procrastination Assessment Scale-Students （PASS）， Beck Anxiety Inventory （BAI） and Cognitive Emotion Regulation Questionnaire-Chinese version （CERQ-C） were used to conduct the survey. Pearson correlation analysis was adopted to examine the correlation among all variables， and Process 3.5 macro program was utilized to determine the mediation effect of cognitive emotion regulation strategies and anxiety on the relationship between academic procrastination and mobile phone dependence among college students. Results①PASS scores were positively correlated with the scores on CERQ-C negative cognitive emotion regulation strategy， BAI and MPAI （r=0.374， 0.229， 0.661， P<0.01）， CERQ-C negative cognitive emotion regulation strategy scores were positively correlated with BAI and MPAI scores （r=0.372， 0.498， P<0.01）， and BAI scores were positively correlated with MPAI scores （r=0.340， P<0.01）. ② Both negative cognitive emotion regulation strategy and anxiety exerted an mediation effect on the relationship between academic procrastination and mobile phone dependence among college students， with an effect value of 0.094 （95% CI： 0.056~0.137） and 0.013 （95% CI： 0.001~0.029）， and a chained mediation effect of negative cognitive emotion regulation strategy and anxiety on the relationship between academic procrastination and mobile phone dependence among college students was also documented， with an effect value of 0.015 （95% CI： 0.006~0.026）. ConclusionAcademic procrastination is proved to be effective in predicting college students' mobile phone dependence both directly and indirectly through either separate or chained mediation of negative cognitive emotion regulation strategy and anxiety. ［Funded by Social-Science Fund Project in Xinjiang （number， 2023CSH068）； Scientific Research Projects of Universities in Xinjiang Uygur Autonomous Region （number， XJEDU2023P081）］

Purpose To explore the clinicopathological features and potential clinical value of marginal zone lym-phoma(MZL)derived from T-bet positive memory B cell.Methods Clinical data of 67 cases of MZL were collected.Hematoxylin-eosin,immunohistochemistry,and multiple immunofluorescence stains,B cell receptor high throughput sequencing technology were used to study the histology,immunophenotype,and immunoglobulin heavy chain variable gene(IGHV)repertoire.Results T-bet was expressed in some MZL patients(34/67,50.75％),which was correla-ted with clinicopathological characteristics such as gender,clinical stage,and Ki67 proliferation index(P＜0.05),and also the progression-free survival was poor(P=0.012 2).T-bet positivity was a risk factor affecting the progres-sion of MZL.Microscopically,T-bet positive MZL frequently presented T-bet positive tumor B cells surrounded follicu-lar germinal center,"MALT ball"-type lymphoepithelial lesions,and IgG positive neoplastic plasma cells(P＜0.05).T-bet had no biased influence on the VH gene usage(P＞0.05).The common VH families were IGHV4 and IGHV3,and the segments were IGHV4-34 and IGHV3-30.The positivity of T-bet was associated with somatic hypermutation(SHM)state(P=0.014 9).The SHM was mainly in the range of 2％-4.9％in T-bet positive MZL,while in T-bet negative MZL the SHM was mostly greater than 5％.The VH gene usage was not correlated with the clinicopathological features of patients(P＞0.05).IGHV4 was correlated with progression-free survival in T-bet positive MZL(P=0.038 2).Conclusion The expression of T-bet in MZL is closely related to the clinicopathological features such as histology,plasma cell immunophenotype and IGHV gene repertoire,and the prognosis of patients is poor,which may be a potential molecular marker affecting the progression of MZL.

Patient-Reported Outcomes(PRO)is a subjective outcome indicator based on the concept of"patient-centered",in which patients report their own information such as health status,functional status,and treatment feelings,which is an ef-fective supplement to traditional objective outcome indicators.Based on the development status of the Patient Reported Outcome Measure(PROM),it systematically analyzed the concepts related to PRO with the goal of clarifying the Patient Experience Data(PED)with research value,and proposed six core types of PROs in the medical field,including health-related quality of life,health preference,health behavior,symptom burden,functional status and patient-reported experience.For each type of PRO,the key characteristics of the study were analyzed,the evidence and application directions of related PED and the production based on PED were described,and the existing international mainstream PROMs were reviewed.It is hoped that the connotation of PRO-related concepts can be comprehensively expounded,and PEDs with research significance and value can be explored,so as to provide guidance for the focus of PRO-related research in China,so as to promote the application and development of PRO in China.