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.

OBJECTIVE To explore the potential mechanisms of astragalin （AG） in allevating ulcerative colitis （UC） in mice through modulation of the intestinal flora. METHODS Male C57BL/6 mice were randomly divided into normal group （CON group）， model group [dextran sodium sulfate （DSS） group]， 5-aminosalicylic acid group （5-ASA group）， AG low-dose group and high-dose group （AGL and AGH groups）， with 8 mice in each group. The mice UC model was established by drinking 3% DSS solution continuously for 7 days in all groups except the CON group. After that， 3% DSS solution was replaced by water， and the mice of each drug group were gavaged with the corresponding drug solution. Mice in the CON and DSS groups were gavaged with an equal volume of normal saline， once a day， for 7 days. After the last gavage， the body weight change index， disease activity index （DAI） score， colon length and spleen index， and levels of inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6） were compared among the mice in each group； pathological changes in colonic tissues of the mice were observed in each group， and the pathological score and the percentage of goblet cells were compared； mRNA expressions of barrier-related factors [occludin and ZO-1] and inflammation-related factors [silencing information regulatory factor 1 （SIRT1）， c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK）] were detected in each group of mice； the changes in the intestinal flora of mice in each group were analyzed and the contents of intestinal metabolites short-chain fatty acids （SCFAs） was determined. Using DSS and AG-treated fecal bacterial liquid as an intervention， the mechanism of anti-UC effect of AG was further verified by a fecal microbiota transplant experiment. RESULTS Compared with the CON group， the intestinal mucosal structure of mice in the DSS group was severely damaged， with obvious infiltration of inflammatory cells collapsing the wall； their body weight change index， colon length， the percentage of goblet cells， mRNA expressions of occludin， ZO-1 and SIRT1， Chao1 and Shannon indexes， and contents of acetic acid and butyric acid were significantly reduced， shortened or down-regulated （P＜0.05）； however， DAI score， spleen index， levels of inflammatory factors， pathological score， as well as mRNA expressions of p38 MAPK and JNK， were all significantly increased or up-regulated （P＜0.05）. Compared with the DSS group， colon tissue lesions of AG mice in all dose groups showed different degrees of improvement， and the above quantitative indexes were generally regressed （P＜0.05）， and the intervention effect of AG-treated fecal bacterial fluid was basically the same as that of AG. CONCLUSIONS AG can improve relevant symptoms in UC mice and reduce their inflammatory response and colonic histopathological changes. The above effects may be related to regulating the diversity of intestinal flora in mice， increasing the contents of butyric acid and propionic acid， and promoting the repair of the colonic mucosal barrier， thus regulating the expressions of genes related to the SIRT1/p38 MAPK inflammatory pathway.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

BACKGROUND:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.

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.

Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

Objective:To explore the neuropathological characteristics of brain tissues from autopsy of patients with schizophrenia.Methods:Forty-two autopsy cases from National Human Brain Bank for Health and Disease, School of Medicine, Zhejiang University from January 2013 to December 2024 were selected as research subjects, among which, 21 were schizophrenia patients(schizophrenia group) and 21 were non-schizophrenia patients (non-schizophrenia group). Clinical data of patients from the two groups were compared. HE staining was used to detect the pathological changes such as infarction, hemorrhage and arteriosclerosis in the brain tissues, silver-nitrate staining was used to detect the amyloid plaques in the brain tissues, Congo red staining was used to detect the pathological changes related to cerebral amyloid angiopathy (CAA) in the brain tissues, modified Gallyas silver staining was used to detect the neurofibrillary tangles in the brain tissues, and immunohistochemical staining was used to detect the expressions of phosphorylated tau protein, β-amyloid protein (Aβ), TAR DNA binding protein 43 (TDP-43), and α-synuclein in the brain tissues. Alzheimer's disease neuropathologic change (ADNC), primary age-related tauopathy (PART), limbic-predominant age-related TDP-43 encephalopathy (LATE), aging-related tau astrogliopathy (ARTAG), Lewy body disease (LBD), and cerebrovascular disease (CVD)-related pathological changes in the brain tissues were evaluated, and differences in positive rates of the above pathological changes were compared.Results:No significant difference in gender, age of death, brain weight, or apolipoprotein E genotype was noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Six schizophrenia patients exhibited low-to-intermediate ADNC, including 4 with low ADNC and 2 with intermediate ADNC. Compared with the non-schizophrenia group, the positive rates of ADNC- and CVD-related pathological changes in the schizophrenia group were significantly higher (0 vs. 28.6%; 9.5% vs. 47.6%, P<0.05). No significant differences in positive rates of PART-, LATE-, ARTAG-, and LBD-related pathological changes were noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Conclusion:Schizophrenia patients show high proportions of ADNC- and CVD-related pathological changes, but relatively low ADNC severity.

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.