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.

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

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）］

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.

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.

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 This study aims to investigate the effects of acupuncture on the spatial learning and memory capacities,the morphological characteristics of hippocampal neurons,the components of extracellular matrix,as well as the structure of the blood-brain barrier in SAMP8 mice.Moreover,it endeavors to explore the underlying mechanism through which the"Tongdu Qishen"(activating governor vessel and awakening spirit)acupuncture method ameliorates the cognitive function and modulates cerebral blood flow in SAMP8 mice.Methods Twenty 6-month-old male SAMP8 mice were randomly allocated into a model group and an electroacupuncture group,with ten mice in each group.Additionally,ten homologous 6-month-old male SAMR1 mice were designated as the normal control group.In the electroacupuncture group,the acupoint"Renzhong"(GV 26)was punctured using a quick insertion technique,while"Baihui"(GV 20)and"Yintang"(EX-HN 3)were punctured via a transverse insertion method.Subsequently,the needle handles were connected to an electroacupuncture apparatus,which was set to operate with a dense-sparse wave at a frequency of 100 Hz/2 Hz and an electric current of 2 mA.Each session of acupuncture lasted for 20 minutes and was conducted once a day for a consecutive period of 28 days.The normal group,the model group,and the electroacupuncture group all underwent identical fixation and restraint procedures to ensure consistent experimental conditions.The Morris water maze was employed to evaluate the spatial learning and memory abilities of the mice.The Nissl staining technique was utilized to assess the alterations in hippocampal neurons of SAMP8 mice.The laser speckle imaging system was adopted to measure the cerebral blood flow of the mice in each group.Transmission electron microscopy was applied to observe the ultrastructure of the blood-brain barrier within the frontal cortex tissue of the SAMP8 mice's brains.The Western blotting method was used to detect the expressions of Collagen-Ⅳ and Fibronectin in the brain tissues of SAMP8 mice.Results In comparison with the model group,the"Tongdu Qishen"acupuncture method demonstrated a significant efficacy in improving the spatial learning and memory abilities of SAMP8 mice(P<0.05).It also effectively alleviated the degeneration of hippocampal neurons,remarkably increased the cerebral blood flow perfusion volume of SAMP8 mice(P<0.05),ameliorated the damage to the blood-brain barrier structure,significantly upregulated the content of Collagen-Ⅳ(P<0.05),and significantly downregulated the content of Fibronectin(P<0.0001).Conclusion The"Tongdu Qishen"acupuncture method is capable of favorably regulating the extracellular matrix of SAMP8 mice,thereby improving cerebral blood flow and ultimately enhancing their learning and memory abilities.

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.

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.

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.