ObjectiveTo analyze the incidence and spatiotemporal distribution of typhus fever in Baoshan City, Yunnan Province from 2005 to 2023, to identify high-risk populations and regions, so as to provide a scientific basis for optimizing the allocation of local prevention and control resources and developing targeted intervention measures. MethodsData of typhus fever cases in Baoshan City from 2005 to 2023 were obtained from the Infectious Disease Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution of typhus fever cases. Spatial clustering was assessed using spatial dynamic window scan statistics (circular and elliptical windows), flexible spatial scan statistics, and local spatial autocorrelation methods (including local Moran’s I, local Geary’s C, and Getis-Ord G_i*). Retrospective spatiotemporal scan statistics were employed to detect spatiotemporal clusters. ResultsA total of 1 099 typhus fever cases were reported in Baoshan City from 2005 to 2023. The incidence rate peaked at 6.31/ 100 000 in 2007, followed by a decline until reaching its lowest level at 0.21/100 000 in 2015 , and subsequently rebounded during 2016‒2023. The highest proportion of cases was among children under 10 years of age (31.12%), and the top three occupations of cases were farmers, students, and children, accounting for 88.62% of all cases. Cases occurred predominantly between June and September each year. The incidence was relatively high in Jiucheng Town (62.58/100 000), Yaoguan Town (57.15/100 000), and Dianyang Town (46.81/100 000) of Shidian County. Spatial clustering analyses indicated that high-risk areas were mainly located in the southern part of Baoshan City, showing a south-to-north trend. Spatiotemporal scan analyses identified five clusters, with the most likely cluster centered around Yaoguan Town, covering ten towns (subdistricts) during the period 2007‒2010. ConclusionThe incidence of typhus fever in Baoshan City exhibits a clear seasonal and spatial clustering pattern, with peak incidence occurring in summer and autumn. Spatially, cases are primarily distributed in the southern part of Baoshan City, and high-risk clusters exhibit a south-to-north trend. Farmers, students, and children are the high-risk groups.

Currently,acquired immune deficiency syndrome(AIDS)has emerged as a global public health crisis that profoundly compromises human immune defenses.By systematically dismantling the im-mune system,human immunodeficiency virus(HIV)renders individuals vulnerable to opportunistic in-fections and malignancies,ultimately culminating in AIDS progression.It is urgent to eradicate the latent HIV virus and achieve a functional cure,thus limiting the development of AIDS and improving the quality of patients.Epigenetics investigates heritable alterations in gene expression that occur independently of DNA sequence.The intricate regulation of HIV gene expression is orchestrated through multifaceted epi-genetic mechanisms involving both viral and host factors.Understanding the epigenetic mechanisms asso-ciated with HIV infection is crucial for clearing latent viruses and achieving control and treatment of AIDS in the future.Therefore,we will discuss the epigenetic regulatory patterns and mechanisms involved in HIV infection,particularly emphasize on four principal mechanisms:DNA methylation,histone modifica-tion,non-coding RNA regulation and RNA modification.We comprehensively analyze how these regula-tory factors influence the viral life cycle,particularly regarding latency establishment,reactivation dy-namics,and persistent infection maintenance.Furthermore,we delineate the interplay between epigenet-ic regulators and key cellular signaling pathways during HIV pathogenesis.The review culminates in a critical appraisal of recent breakthroughs and persistent challenges in epigenetics-based therapeutic strate-gies,while highlighting innovative approaches for functional cure development.By elucidating the pivotal role of epigenetic regulation in HIV latency,this review aims to establish a novel theoretical foundation and innovative research directions for next-generation AIDS therapeutics rooted in epigenetic modifica-tion.

Objective To investigate the effect of perindopril on the nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)/NOD-like receptor protein 3(NLRP3)signaling pathway in rat liver fibrosis induced by thioacetamide(TAA).Methods Thirty-two SD rats were randomly divided into the blank group,the model group(TAA 200 mg/kg,twice a week for 6 weeks)and the low/high dose group(TAA+perindopril 2/8 mg/kg),with 8 rats in each group.Two weeks after modeling,the administration group was given the corresponding dose of perindopril by gavage(for 4 weeks).At the end of the 6th week,liver pathological sections were used to observe pathological changes of liver tissue and degrees of fibrosis and inflammation.The biochemical analyzer was used to detect alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Enzyme-linked immunosorbent assay(ELISA)was used to detect NLRP3 and IL-1β.Immunohistochemistry was used to detect NOX4,NLRP3,Caspase-1,IL-1β protein and α-smooth muscle agonist protein(α-SMA).Results Compared with the blank group,liver collagen fibers were significantly proliferated in the model group,a large number of inflammatory cells infiltrated,and serum levels of ALT and AST,as well as NLRP3 and IL-1β in rats were significantly increased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue increased significantly(P<0.05).Compared with the model group,the proliferation of collagen fibers and inflammatory infiltration were significantly reduced in both the low-dose and high-dose groups,and serum levels of ALT and AST,NLRP3 and IL-1β in rats were significantly decreased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue decreased significantly(P<0.05).Moreover,the degree of liver fibrosis reduction in rats was better in the high-dose group than that in the low-dose group.Conclusion Perindopril may regulate the NLRP3 signaling pathway by inhibiting the expression of NOX4,thereby reducing oxidative stress damage and inflammatory responses and thus delaying the process of liver fibrosis.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

Objective To explore the prediction efficiency of Ki-67 expression status in pituitary adenoma(PA)based on a joint model of siamese network and transfer learning.Methods The preoperative MR T1WI enhanced sequence images of 370 patients with PA diagnosed by surgery and pathology were retrospectively collected.According to the results of immunohistochemical,all patients were divided into high proliferation index group(Ki-67≥3,n=97)and low proliferation index group(Ki-67＜3,n=273),and all the sample data were randomly divided into training set and test set according to the ratio of 7∶3.Two single predictive models,ResNet-50 and VGGNet-16 and combined them with the siamese network and transfer learning were built.The prediction efficiency of different models were evaluated via accuracy rate,precision rate,recall rate,F1 score and receiver operating characteristic(ROC)curve as the main criteria.Results Compared with a single predictive model,the model combined with siamese network and transfer learning showed a better performance for predicting the Ki-67 of PA.Additionally,the ResNet-50 joint model exhibited the superior predictive performance.The accuracy rate was 0.872 7,the precision rate was 0.812 5,the recall rate was 0.764 7,the F1 score was 0.787 9,and the area under the curve(AUC)was 0.841 6.Conclusion The joint model based on siamese network and transfer learning exhibits a higher efficiency for predicting the Ki-67 expression status in PA,which can help the clinicians to formulate more personalized treatment for the patients.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Objective To investigate the effect of perindopril on the nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)/NOD-like receptor protein 3(NLRP3)signaling pathway in rat liver fibrosis induced by thioacetamide(TAA).Methods Thirty-two SD rats were randomly divided into the blank group,the model group(TAA 200 mg/kg,twice a week for 6 weeks)and the low/high dose group(TAA+perindopril 2/8 mg/kg),with 8 rats in each group.Two weeks after modeling,the administration group was given the corresponding dose of perindopril by gavage(for 4 weeks).At the end of the 6th week,liver pathological sections were used to observe pathological changes of liver tissue and degrees of fibrosis and inflammation.The biochemical analyzer was used to detect alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Enzyme-linked immunosorbent assay(ELISA)was used to detect NLRP3 and IL-1β.Immunohistochemistry was used to detect NOX4,NLRP3,Caspase-1,IL-1β protein and α-smooth muscle agonist protein(α-SMA).Results Compared with the blank group,liver collagen fibers were significantly proliferated in the model group,a large number of inflammatory cells infiltrated,and serum levels of ALT and AST,as well as NLRP3 and IL-1β in rats were significantly increased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue increased significantly(P<0.05).Compared with the model group,the proliferation of collagen fibers and inflammatory infiltration were significantly reduced in both the low-dose and high-dose groups,and serum levels of ALT and AST,NLRP3 and IL-1β in rats were significantly decreased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue decreased significantly(P<0.05).Moreover,the degree of liver fibrosis reduction in rats was better in the high-dose group than that in the low-dose group.Conclusion Perindopril may regulate the NLRP3 signaling pathway by inhibiting the expression of NOX4,thereby reducing oxidative stress damage and inflammatory responses and thus delaying the process of liver fibrosis.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

Objective To explore the prediction efficiency of Ki-67 expression status in pituitary adenoma(PA)based on a joint model of siamese network and transfer learning.Methods The preoperative MR T1WI enhanced sequence images of 370 patients with PA diagnosed by surgery and pathology were retrospectively collected.According to the results of immunohistochemical,all patients were divided into high proliferation index group(Ki-67≥3,n=97)and low proliferation index group(Ki-67＜3,n=273),and all the sample data were randomly divided into training set and test set according to the ratio of 7∶3.Two single predictive models,ResNet-50 and VGGNet-16 and combined them with the siamese network and transfer learning were built.The prediction efficiency of different models were evaluated via accuracy rate,precision rate,recall rate,F1 score and receiver operating characteristic(ROC)curve as the main criteria.Results Compared with a single predictive model,the model combined with siamese network and transfer learning showed a better performance for predicting the Ki-67 of PA.Additionally,the ResNet-50 joint model exhibited the superior predictive performance.The accuracy rate was 0.872 7,the precision rate was 0.812 5,the recall rate was 0.764 7,the F1 score was 0.787 9,and the area under the curve(AUC)was 0.841 6.Conclusion The joint model based on siamese network and transfer learning exhibits a higher efficiency for predicting the Ki-67 expression status in PA,which can help the clinicians to formulate more personalized treatment for the patients.

Currently,acquired immune deficiency syndrome(AIDS)has emerged as a global public health crisis that profoundly compromises human immune defenses.By systematically dismantling the im-mune system,human immunodeficiency virus(HIV)renders individuals vulnerable to opportunistic in-fections and malignancies,ultimately culminating in AIDS progression.It is urgent to eradicate the latent HIV virus and achieve a functional cure,thus limiting the development of AIDS and improving the quality of patients.Epigenetics investigates heritable alterations in gene expression that occur independently of DNA sequence.The intricate regulation of HIV gene expression is orchestrated through multifaceted epi-genetic mechanisms involving both viral and host factors.Understanding the epigenetic mechanisms asso-ciated with HIV infection is crucial for clearing latent viruses and achieving control and treatment of AIDS in the future.Therefore,we will discuss the epigenetic regulatory patterns and mechanisms involved in HIV infection,particularly emphasize on four principal mechanisms:DNA methylation,histone modifica-tion,non-coding RNA regulation and RNA modification.We comprehensively analyze how these regula-tory factors influence the viral life cycle,particularly regarding latency establishment,reactivation dy-namics,and persistent infection maintenance.Furthermore,we delineate the interplay between epigenet-ic regulators and key cellular signaling pathways during HIV pathogenesis.The review culminates in a critical appraisal of recent breakthroughs and persistent challenges in epigenetics-based therapeutic strate-gies,while highlighting innovative approaches for functional cure development.By elucidating the pivotal role of epigenetic regulation in HIV latency,this review aims to establish a novel theoretical foundation and innovative research directions for next-generation AIDS therapeutics rooted in epigenetic modifica-tion.