ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, is primarily airborne and remains a global health problem, especially in resource-limited countries and regions. The emergence of drug resistance in M. tuberculosis has rendered the existing means ineffective in the treatment of TB. Therefore, research in new therapeutic directions has become imperative. In this review, we outline functional peptides in terms of the mechanisms of action, anti-TB attempts, advantages and disadvantages, and latest advances, aiming to analyze the research progress in anti-TB peptides. Furthermore, we investigate the potential applications of bioactive compounds found in traditional Chinese Medicine within the context of peptides.

Alzheimer's disease(AD)is a neurodegenerative disease characterized by cognitive impairment,loss of life function,mental and behavioral abnormalities.It is the leading cause of dementia in the elderly.The prevalence of mild cognitive impairment(MCI)in the elderly over 60 years old in China is 15.5％,and the prevalence of AD is 3.9％,which becomes a major public health challenge for China to enter the rapid growth stage of aging.Early diagnosis and early intervention are the keys to improving the prognosis of AD and reducing mortality.MCI is an important window for early intervention of AD,but how to detect MCI in the community conveniently and economically remains to be explored.This article reviews the research progress of biosample-based biosensors,retinal imaging,and digital biomarkers,and provides conceptual ideas for AD screening in community-oriented primary care.

Objective:To study the impact of fluoride exposure through drinking water on the risk of hypertension among residents in Jishan County, Shanxi Province.Methods:From March to April 2023, a cluster sampling method was used to select permanent residents aged ≥18 years and residing for ≥10 years in 12 villages in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province as the survey subjects. A questionnaire survey, physical examination, and morning urinary fluoride level testing were conducted. The least absolute shrinkage and selection operator (Lasso) regression were used to analyze the key influencing factors of hypertension. Restricted cubic spline was used to evaluate the linear relationship between urinary fluoride and hypertension. Logistic regression was used to analyze the impact of urinary fluoride on hypertension.Results:Finally, 2 453 survey subjects were included, aged (62 ± 10) years, including 1 565 patients (63.80%) with hypertension. There were significant differences in the distribution of age, gender, education level, annual household income, body mass index (BMI), and the level and distribution of urinary fluoride between hypertension group and normal blood pressure group ( P < 0.05). The Lasso regression results showed that age, education level, BMI, and urinary fluoride were the key influencing factors of hypertension, with coefficients of 1.04, - 0.12, 0.24 and 0.01, respectively. The results of the restricted cubic spline showed that there was a linear relationship between urinary fluoride and hypertension after adjusting for age, education level, and BMI ( Poverall = 0.018, Pnonlinear = 0.482). The logistic regression results showed that after adjusting for age, education level, and BMI, urinary fluoride > 4.68 mg/L was a risk factor for hypertension ( OR = 1.42, 95% CI: 1.10 - 1.84, P = 0.007). Conclusion:High urinary fluoride is a risk factor for hypertension in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province.

Objective To explore the clinical characteristics as well as molecular epidemiological features of resis-tance genes and virulence genes of carbapenem-resistant Klebsiella pneumoniae(CRKP)infection in a region,and provide scientific basis for the prevention,treatment,and epidemiological study of CRKP.Methods 60 non-repeti-tive CRKP strains isolated clinically from Puyang Oilfield General Hospital from November 2023 to September 2024 were analyzed retrospectively.Antimicrobial susceptibility testing was performed using VITEK 2 Compact automa-tic microbial analyzer,K-B disk diffusion method,and micro-broth dilution method.Mucus phenotype of bacterial strains was identified by string test.Carbapenemase was detected by carbapenemase inhibitor enhancement assay.Molecular features,such as multi-locus sequence typing(MLST),capsule serotypes,resistance genes,virulence genes,plasmid replication types of strains,as well as the genetic and evolutionary relationships of strains were de-termined by whole genome sequencing and bioinformatics analysis.Results CRKP strains were mainly isolated from elderly male hospitalized patients.Specimens were mostly from sputum(71.67％),mainly distributed in depart-ment of respiratory medicine(30.00％).All strains were highly resistant to multiple commonly used antimicrobial agents,only with high susceptibility rates to cefotaxime/avibactam,tigecycline,and polymyxin B(＞60.00％).Two CRKP strains were positive for string test.95.00％of the strains produced class A serine carbapenemase.All strains carried fluoroquinolone,phosphomycin,β-lactam,and aminoglycoside resistance genes;enterobactin,Esche-richia coli common pilus(ECP),and outer membrane protein-related virulence genes;as well as plasmids from the IncF plasmid family.Carbapenemase gene was mainly blaKPC-2(95.00％),and the major capsule serotype was KL19(43.33％).In MLST,ST11(51.67％)was the dominant clone group,and ST11-KL62(n=12)was the dominant subtype.Conclusion CRKP in this hospital is highly resistant to multiple commonly used antimicrobial agents,and its mechanism of resistance to carbapenems is mainly related to the presence of blaKPC-2 resistance gene.All strains have coexisting multiple resistance genes and virulence genes,and show a phenomenon of multi-clone transmission.ST11 is the dominant clone group,and ST11-KL62 is the main prevalent subclone type.

Purpose To evaluate the predictive performance of mean apparent propagator-magnetic resonance imaging(MAP-MRI)combined with habitat analysis for determining O6-methylguanine-DNA methyltransferase(MGMT)promoter methylation status in glioma.Materials and Methods This retrospective study analyzed MRI and clinical data from 55 patients with surgically confirmed glioma at Fujian Medical University Union Hospital from January 2019 to December 2023.All patients underwent structural and diffusion-weighted imaging.Three-dimensional volumes of interest were delineated in the tumor solid region using ImageJ software.The nn-FAE tool was used to segment the tumor solid region into two habitat subregions based on mean diffusivity(MD)maps:high-MD and low-MD habitats.Average diffusion parameter values were extracted from the entire tumor solid region and each habitat subregion.Differences in parameters between methylated and unmethylated groups were compared,and the area under the curve was calculated.Results Among 55 patients,significant differences were observed in all MAP-MRI parameters and MD in the tumor solid region and low-MD habitat,as well as all parameters in the high-MD habitat between methylated and unmethylated groups(t/Z=-3.780-3.153,all P<0.05).The return-to-origin probability(RTOP)in the low-MD habitat demonstrated the highest diagnostic performance,with the area under the curve improving from 0.771 before habitat analysis to 0.827 after habitat analysis.In the high-grade subgroup,significant differences were observed in return-to-axis probability(RTAP)and RTOP in the tumor solid region;RTOP,non-Gaussianity,non-Gaussianity axial,and RTAP in the low-MD habitat;and non-Gaussianity in the high-MD habitat(t/Z=-2.820--1.976,all P<0.05).RTOP in the low-MD habitat again showed optimal diagnostic efficacy(the area under the curve 0.725 before habitat analysis,0.798 after).Multivariate analysis identified RTAP and RTOP in the tumor solid region and low-MD habitat as independent predictors of MGMT methylation.Conclusion MAP-MRI diffusion parameters demonstrate the ability to predict MGMT promoter methylation status in glioma,with superior performance compared with diffusion tensor imaging.Habitat imaging further enhances the predictive efficacy of MAP-MRI parameters for MGMT promoter methylation.

Objective To explore the clinical characteristics as well as molecular epidemiological features of resis-tance genes and virulence genes of carbapenem-resistant Klebsiella pneumoniae(CRKP)infection in a region,and provide scientific basis for the prevention,treatment,and epidemiological study of CRKP.Methods 60 non-repeti-tive CRKP strains isolated clinically from Puyang Oilfield General Hospital from November 2023 to September 2024 were analyzed retrospectively.Antimicrobial susceptibility testing was performed using VITEK 2 Compact automa-tic microbial analyzer,K-B disk diffusion method,and micro-broth dilution method.Mucus phenotype of bacterial strains was identified by string test.Carbapenemase was detected by carbapenemase inhibitor enhancement assay.Molecular features,such as multi-locus sequence typing(MLST),capsule serotypes,resistance genes,virulence genes,plasmid replication types of strains,as well as the genetic and evolutionary relationships of strains were de-termined by whole genome sequencing and bioinformatics analysis.Results CRKP strains were mainly isolated from elderly male hospitalized patients.Specimens were mostly from sputum(71.67％),mainly distributed in depart-ment of respiratory medicine(30.00％).All strains were highly resistant to multiple commonly used antimicrobial agents,only with high susceptibility rates to cefotaxime/avibactam,tigecycline,and polymyxin B(＞60.00％).Two CRKP strains were positive for string test.95.00％of the strains produced class A serine carbapenemase.All strains carried fluoroquinolone,phosphomycin,β-lactam,and aminoglycoside resistance genes;enterobactin,Esche-richia coli common pilus(ECP),and outer membrane protein-related virulence genes;as well as plasmids from the IncF plasmid family.Carbapenemase gene was mainly blaKPC-2(95.00％),and the major capsule serotype was KL19(43.33％).In MLST,ST11(51.67％)was the dominant clone group,and ST11-KL62(n=12)was the dominant subtype.Conclusion CRKP in this hospital is highly resistant to multiple commonly used antimicrobial agents,and its mechanism of resistance to carbapenems is mainly related to the presence of blaKPC-2 resistance gene.All strains have coexisting multiple resistance genes and virulence genes,and show a phenomenon of multi-clone transmission.ST11 is the dominant clone group,and ST11-KL62 is the main prevalent subclone type.

Objective:To explore the types and characteristics of self-management behaviors among stroke patients, as well as to analyze the influencing factors associated with these different types, providing a reference for developing intervention programs aimed at enhancing self-management behaviors in stroke patients.Methods:This study adopted a cross-sectional survey design. The stroke inpatients were selected through convenience sampling from the Department of Neurology at Huashan Hospital, Fudan University between October 2023 and August 2024. Data collection was conducted using the following instruments: the General Information Questionnaire, Stroke Self-Management Behavior Rating Scale, Self-Efficacy for Managing Chronic Disease 6-Item Scale, Stroke Health Knowledge Questionnaire, Social Support Rating Scale, Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, and the modified Rankin Scale. Stroke patients' self-management behaviors were categorized using systematic cluster analysis, and disordered multi-class Logistic regression was employed to identify the influencing factors associated with each category.Results:Finally, 210 stroke patients were enrolled, there were 148 males and 62 females, aged (60.82 ± 13.05) years. The total score of self-management behavior in stroke patients was (144.18 ± 23.24) points, with a score rate of 56.54%. Systematic cluster analysis identified four distinct self-management behaviors patterns: consistent implementers (25.71%, 54/210); unrealistically optimistic(54.76%, 115/210); optimistically proactive (13.81%, 29/210); and passive and resigned (5.71%, 12/210). Disordered multi-class Logistic regression analysis indicated that higher scores in stroke-related health knowledge were associated with a greater likelihood of being categorized as stable practice type and optimistic proactive type ( OR=1.130, 1.254, both P<0.05). Conversely, increased levels of depression correlate with a higher probability of being classified as passive waiting type ( OR=0.684, 0.722, 0.540, all P<0.05). Additionally, lower modified Rankin Scale scores were linked to an increased tendency to fall into the categories of stable practice type and blind optimism type ( OR=19.759, 23.148, both P<0.05). Conclusions:The self-management behaviors of stroke patients are generally suboptimal and exhibited distinct classification features. Significant differences are observed in stroke health knowledge, depression, and the modified Rankin Scale scores among the four patient types. Healthcare professionals should tailor intervention measures to the characteristics of each type to enhance patients' self-management capacity.

Objective A random forest model was used to analyze the risk of immune reconstitution dysfunction(INR)after antiviral therapy(HAART)in HIV/AIDS patients.Methods A total of 67 HIV/AIDS patients treated in our hospital from January 2019 to December 2022 were selected and all of them received HAART treatment.After 18 months of follow-up,patients were divided into INR group and non-INR group according to prognosis.The clinical data of the two groups were compared,and the importance of the indicators affecting INR in patients was ranked by random forest model,and the related factors affecting INR in HIV/AIDS patients after HAART were analyzed by Logistic regression model.Results During the follow-up period of 18 months,a total of 13(19.40％)of 67 HIV/AIDS patients developed INR.There were statistically significant differences in the time interval from diagnosis to treatment and baseline CD4+T lymphocyte count between INR group and non-INR group(P＜0.05).Random-forest model results showed that variables were ranked in descending order of importance as baseline CD4+T lymphocyte count and time interval between diagnosis and treatment.Logistic multivariate regression analysis showed that more than 1 year between diagnosis and treatment and baseline CD4+T lymphocyte count≤ 200/μl are all risk factors for INR in HIV/AIDS patients after HAART treatment(P＜0.05).Conclusion More than 1 year between diagnosis and treatment and baseline CD4+T lymphocyte count≤200/μl are all risk factors for INR in HIV/AIDS patients after HAART.In addition,the random forest model is of great significance for health care workers to identify high-risk groups of INR after HAART and formulate intervention plans.

Objective:To investigate the current status of insomnia symptoms and executive function (EF) impairments among adolescents from regions with different economic development levels, and to analyze their relationship with depressive symptoms, so as to provide clues for improved depressive symptoms screening practices.Methods:This population-based cross-sectional study employed a multistage, stratified cluster random sampling method. During November 2017 to January 2018 and December 2018 to January 2019, a total of 2 495 adolescents aged 11 to 18 years were selected from Shanghai, representing a highly developed economic region, and 2 704 adolescents aged 11 to 18 years were selected from Shangrao city, Jiangxi province, representing a less developed economic region. The depressive symptoms were assessed using the short version of the 21-item depression, anxiety, and stress scale, based on which participants were categorized into groups with or without depressive symptoms. Insomnia symptoms and EF impairments were measured using a self-designed insomnia scale and the behavior rating inventory of executive function, respectively. Participants were further classified into 4 subgroups: neither insomnia nor EF impairment, EF impairment only, insomnia only, and comorbid insomnia and EF impairment. Chi-square test was used to compare the differences in basic information of adolescents from different regions. Multivariate Logistic regression models were applied to examine the associations between insomnia, EF impairment, and their combination with depressive symptoms as well as the differences in gender and school-stage among each subgroup.Results:A total of 2 305 adolescents were recruited from Shanghai (1 192 boys and 1 113 girls, 1 266 junior high school students and 1 039 senior high school students) and 2 250 adolescents from Shangrao (1 126 boys and 1 124 girls, 1 146 junior high school students and 1 104 senior high school students). The numbers of adolescents with depressive symptoms, insomnia symptoms and EF impairment in Shanghai were 460 adolescents (20.0%), 907 adolescents (39.3%), and 411 adolescents (17.8%), respectively, all of which were fewer than those in Shangrao, which were 616 adolescents (27.4%), 1 251 adolescents (55.6%), and 524 adolescents (23.3%), respectively (all P<0.001). In Shanghai, the numbers of adolescents with EF impairment only, insomnia only, and comorbid insomnia and EF impairment were 219 adolescents (9.5%), 670 adolescents (29.1%), and 237 adolescents (10.3%), respectively. And in Shangrao, the corresponding numbers were 193 adolescents (8.6%), 865 adolescents (38.4%), and 386 adolescents (17.2%), respectively. Compared to adolescents in Shanghai with neither EF impairment nor insomnia, the risk of depressive symptoms was all higher in adolescents with EF impairment only, insomnia only, and comorbid EF impairment-insomnia ( OR=2.86, 6.48, 20.10; 95% CI 1.57-5.22, 5.09-8.26, 13.66-29.58; all P<0.01). Similar results were observed in adolescents in Shangrao ( OR=3.22, 4.82, 10.91; 95% CI 1.66-6.28, 3.09-7.51, 7.26-16.40; all P<0.01). The analysis of gender and educational stage differences showed that, compared to the group neither EF impairment nor insomnia, the risk of depressive symptoms all higher in the groups with EF impairment only, insomnia only (all P<0.05), and comorbid EF impairment-insomnia, and the risk in comorbid EF impairment-insomnia group was the highest (all P<0.05). Conclusions:Compared with adolescents in regions with underdeveloped economies, those in economically developed regions had lower rates of insomnia, EF impairment, and depression. Both insomnia and EF impairment significantly increase the risk of depressive symptoms. Their coexistence confers the highest risk and therefore warrants particular attention for prevention and intervention efforts.