Objective: To explore the association of physical activity and sugar sweetened beverage consumption with psychological sub health among middle school students in Bao an District, Shenzhen, so as to provide a reference for adolescent mental health promotion. Methods: A questionnaire survey was conducted in November 2024 by a stratified cluster random sampling method to select 6 926 junior and senior middle school students from 5 middle schools in Shenzhen. The questionnaire from Youth Risk Behavior Surveillance System was used to assess the consumption of sugar sweetened beverages, and physical activity Rating Scale was used to assess the level of physical activity, and Brief Instrument on Psychological Health of Youths was used to evaluate the psychological sub health status. The Chi -square test was used to analyze the differences in the detection rates of psychological sub health among different groups of middle school students, and a multivariate Logistic regression model was established to analyze the effects of physical activity and sugar sweetened beverage consumption and their combined effects on the psychological sub health of middle school students. Results: The detection rate of psychological sub health among middle school students in Bao an District, Shenzhen was 18.93%. Multivariate Logistic regression analysis showed that, after controlling for confounding factors such as gender, school stage, family residence, family economic status, parental literacy, academic stress and number of friends, lack of physical activity or excessive sugar sweetened beverage consumption were associated with increased risks of psychological sub health among middle school students ( OR =1.36, 1.45); and the highest risk of psychological sub health was found in middle school students who were lack of physical activity and excessive sugar sweetened beverage consumption ( OR =2.59) ( P <0.01). Further analysis by school stages showed that junior high school students with sufficient physical activity and excessive intake of sugary drinks ( ROR =2.10), lack of physical activity and excessive intake of sugary drinks ( ROR =2.31) were at higher risks of psychological sub health than senior high school students( P <0.05). Conclusions Insufficient physical activity and excessive sugar sweetened beverage consumption are closely associated with an increased risk of psychological sub health among middle school students. Effective interventions should be targeted to reduce the risk of psychological sub health problems among middle school students.

BackgroundSchizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia. ObjectiveTo uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia. MethodsData from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship. ResultsIVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship. ConclusionThis study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］

ObjectiveTo explore the pathological mechanism-syndrome-treatment patterns of approved Chinese patent medicines （CPMs） that treat collateral disorders， providing a reference for the principle of "treating different diseases with the same therapy" in collateral pathology. MethodsCPMs that apply treatment strategies based on collateral disorders were identified from the Pharmacodia database by extracting information from the "efficacy" or "indications" sections of drug package inserts. A database was established to extract the names and compositions of the CPMs， as well as their indications， related traditional Chinese medicine （TCM） symptoms， disease locations （affected areas）， and pathological factors. Frequency statistics were performed. Using the Apriori algorithm， an association rule analysis was conducted on CPMs and disease-location combinations related to the top three most frequent pathological factor combinations. Core formulas for these combinations were identified and analyzed through drug network analysis and MCODE module clustering. ResultsA total of 660 CPMs targeting collateral disorders were retrieved， involving 299 indications， 323 TCM symptoms， 21 disease locations， 19 pathological factors， and 124 pathological factor combinations. The most frequent pathological factor combinations were blood stasis （involved in 109 CPMs， 16.52%）， exogenous wind （外风） -cold-dampness （involved in 43 CPMs， 6.52%）， and qi deficiency-blood stasis （involved in 42 CPMs， 6.36%）. Analysis of the core formulas for these combinations revealed common ingredients such as Honghua （Carthami Flos）， Chuanxiong （Chuanxiong Rhizoma）， Danggui （Angelicae Sinensis Radix）， and Dilong （Pheretima）. ConclusionCollateral disorders involve a wide range of pathogenesis and represent a fundamental mechanism in the onset and development of various diseases， characterized by obstruction and stagnation. The primary therapeutic principle is unblocking of the collaterals. Blood stasis obstructing the collaterals is the core pathological basis， and the strategy of activating blood circulation and resolving stasis to unblock the collaterals should be central to the treatment. The core medication pattern involves combining blood-activating and stasis-resolving herbs with insect-derived medicinals that unblock collaterals. Exogenous wind is often the initiating patholo-gical factor in colla-teral disorders， and the appropriate addition of wind-dispelling herbs can enrich the treatment strategies for such conditions.

Objective We aimed to investigate the hemostatic effect and mechanism of modified Sijunzi Decoction(MSJZT),consisting of tangshen,India bread,largehead atractylodes rhizome,liquorice root,milkvetch root,ass hide glue,and India madder root,on the zebrafish intestinal bleeding model through 5-hydroxytryptamine(5-HT)and its receptors(5-HT2aR,5-HT2bR).Methods Zebrafish at 4 days post fertilization were used as the research object.An intestinal bleeding model was established by induction with 6 μmol/L simvastatin for 24 hours.The zebrafish were divided into normal group,model group,MSJZT low-,mid-and high-concentration groups(55.6,167,500 mg/L),and after modeling,the corresponding concentration of MSJZT was administered.The samples were collected after 24 hours.Platelet count(PLT)and bleeding status were observed.The content of 5-HT and Caspase 3/7 activity were detected by colorimetry.The gene expressions of 5-HT2aR,5-HT2bR and serotonin transporter(SERT)were detected by real-time PCR.The protein expressions of protein kinase B(AKT),phosphorylated AKT(p-AKT),extracellular signal-regulated protein kinase(ERK),and phosphorylated ERK(p-ERK)were detected by Western blotting.Results The intestinal bleeding rate in the model group was 70.0%,and that in the MSJZT low-,mid-and high-concentration groups was 36.7%,40.0%,and 80.0%,respectively;the intestinal hemostatic effect was 54%,52%,and 7%,respectively.Compared with the model group,the PLT in the MSJZT low-and mid-concentration groups decreased;the content of 5-HT in all MSJZT groups increased,and the gene expressions of 5-HT2aR and 5-HT2bR were up-regulated.The gene expression of SERT was up-regulated in the low-and mid-concentration groups;the Caspase 3/7 activity in the mid-and high-concentration groups was reduced;the expressions of p-AKT and p-ERK proteins were up-regulated in the low-and mid-concentration groups(all P<0.05).Conclusion MSJZT can reduce the incidence and severity of intestinal bleeding in zebrafish intestinal bleeding models.The mechanism may be achieved by activating AKT and ERK signaling pathways through 5-HT and its receptors.

Objective:To summarize the incidence of cerebral venous reflux (CVR) in patients with recent small subcortical infarct (RSSI) and explore its correlation with enlarged perivascular spaces (EPVS).Methods:Patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022 were included. The baseline demographic data, medical history, and laboratory results of the patients were collected. CVR was assessed by time-of-flight magnetic resonance angiography. Patients were stratified into 2 groups based on the presence (CVR group) or absence of CVR (non-CVR group), and baseline characteristics as well as laboratory test results were compared between the 2 groups. The location and number of EPVS were evaluated using a visual grading scale, with EPVS with higher scores defined as high-grade EPVS (HEPVS). Simultaneous evaluation of cerebral white matter hyperintensities and lacunar infarctions was conducted, followed by intergroup comparisons. The relationship between EPVS and CVR was studied using multiple Logistic regression analysis.Results:A total of 571 patients with RSSI in the lentiform artery area were ultimately included, including 180 females (31.5%). Their age was (59.37±12.87) years. Among them, 73 patients (12.8%) exhibited CVR based on imaging findings, so the incidence of CVR was 12.8%. In comparison between the CVR group ( n=73) and the non-CVR group ( n=498), the proportion of females [21.9% (16/73) vs 32.9% (164/498), χ 2=3.578, P=0.059] was lower and the proportion of history of smoking [38.4% (28/73) vs 27.7% (138/498), χ 2=3.499, P=0.061] was higher in the CVR group, but without statistical significance. Additionally, the history of alcohol consumption [34.2% (25/73) vs 21.7% (108/498), χ 2=5.621, P=0.018] and the proportion of patients with concomitant HEPVS in the basal ganglia area [41.1% (30/73) vs 25.3% (126/498), χ 2=7.999, P=0.005] was higher in the CVR group with statistical significance. Multiple Logistic regression analysis showed that HEPVS in the basal ganglia region remained independently associated with CVR ( OR=1.988, 95% CI 1.190-3.320, P=0.009). Conclusion:EPVS in the basal ganglia region is significantly associated with CVR in the RSSI population, suggesting that venous dysfunction may be closely related to the formation of EPVS.

Objective:To investigate interleukin-37 (IL-37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL-37 on CD8 + T cell function in DKD patients. Methods:A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8 + T cells were measured by flow cytometry. CD8 + T cells were purified, and were stimulated with recombinant IL-37. CD8 + T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results:Plasma IL-37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] ( t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL-37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL-37 level was negatively correlated with urea nitrogen ( r=-0.313, P=0.032) and creatinine ( r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) ( r s=0.478, P<0.001) in DKD patients. IL-1R8 + CD8 + cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) ( t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα + CD8 + cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8 + T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8 + T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8 + T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL-37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL-37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion:IL-37 level is reduced in DKD patients.Exogenous IL-37 suppresses the cytotoxicity of CD8 + T cells in DKD patients.

Objective To investigate the effect of Yantiao Fang on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating the Rho/ROCK signaling pathway.Methods Seventy BALB/c mice were randomly divided into normal,sham,and model groups.Except for normal and sham groups,mice were subjected to cecal ligation and perforation to establish a mouse model of acute gastrointestinal injury caused by sepsis.The mouse models were randomly divided into model,Low,Medium,and High dose of Yantiao Fang,and ROCK inhibitor groups.Histopathological changes of the ileum were observed by HE staining.Serum levels of IL-1β,IL-6,TNF-α,and IL-10 were measured by ELISA.PCNA and Ki-67 expression was detected by immunohistochemistry.Cleaved caspase3 and Bax expression was detected by Western blot.ROCK and MLC mRNA expression in the ileum was measured by RT-qPCR.Results Compared with normal and sham groups,Chiu's pathological score,proinflammatory factor(IL-1β,IL-6,and TNF-α)levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were increased in the model group(P＜0.05).Moreover,anti-inflammatory mediator IL-10 and expression of PCNA and Ki-67 in the ileum were decreased in the model group(P＜0.05).Compared with the model group,histopathological changes of the ileum in all Yantiao Fang groups were improved by various degrees with the increase in dose.Chiu's pathological score,IL-1β,IL-6,and TNF-α serum levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were decreased in Yantian Fang groups(P＜0.05).The IL-10 level and expression of PCNA and Ki-67 in the ileum were increased in Yantian Fang groups(P＜0.05).Conclusions Yantiao Fang may inhibit apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury due to sepsis by regulating the Rho/ROCK signaling pathway,thereby alleviating intestinal tissue inflammation and ultimately preventing intestinal mucosal tissue injury.

Objective:To explore the correlation between high cholinergic pathway signaling and cognitive function in patients with Parkinson disease(PD) accompanied with sleep disorder.Methods:PD patients admitted from 2017 to 2022 were divided into PD with sleep disorder group (PD-SD group) ( n=56) and PD without sleep disorder group (PD-NSD group) ( n=41) according to the Parkinson's disease sleep scale (PDSS) score. All participants underwent magnetic resonance imaging examination.All patients were evaluated by the PDSS, Hoehn-Yahr (H-Y), Montreal cognitive assessment scale (MoCA), and cholinergic pathways hyper intensities scale (CHIPS). The difference of cognitive function between the two groups and the correlation between CHIPS and cognitive function were analyzed.Independent sample t-test, Spearman correlation analysis, and binary Logistic regression analysis were performed on the data by SPSS 26.0 statistical software. Results:(1)The MoCA score of the PD-SD group (22.00 (5.00)) was lower than that of the PD-NSD group (26.00 (5.00)) ( Z=-3.830, P<0.05). The total and all aspects scores of CHIPS in PD-SD group were higher than those in PD-NSD group(the total score of the low external capsule: 12.00(8.00), 0(8.00), the total score of the high external capsule: 12.00(2.00), 6.00(9.00), the total score of the radial crown: 8.00(0), 4.00(4.00), the total score of the centrum semiovale: 3.00(4.00), 0(2.00), the total score of the right side: 16.00(9.00), 5.00(10.00), the total score of the left side: 17.00(6.00), 7.00(9.00), the total score of CHIPS: 32.00(14.00), 14.00(20.00))( Z=-5.081, -5.873, -4.933, -3.211, -5.562, -6.232, -5.995, all P<0.05). (2)The correlation analysis between the score of CHIPS and cognitive function in the PD-SD group showed that, the total score of the low external capsule ( r=-0.286), the total score of the centrum semiovale ( r=-0.307), the total score of the right side ( r=-0.376), the total score of the left side ( r=-0.284) and the total score of CHIPS ( r=-0.349) were negatively correlated with MoCA(all P<0.05). (3)Binary Logistic regression analysis showed that white matter lesions in centrum semiovale, low inner capsule, right and left leukodystrophy were not influence factors for cognitive impairment (all P>0.05). Conclusion:PD patients with sleep disorders have lower cognitive function scores, higher CHIPS scores, and significant changes in white matter lesions compared to those without sleep disorders. In PD patients with sleep disorders, the higher the CHIPS score, the lower the cognitive function score, and the more significant the rate of cognitive impairment occurrence and development.

BACKGROUND: Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment. Long non-coding RNA (lncRNA) THAP7-AS1 is known to be highly expressed in gastric cancer, but has been less studied in other cancers. The aim of the study is to explore the role and mechanism of methyltransferase-like 3 (METTL3) mediated up-regulation of N6-methyladenosine (m6A) modified lncRNA THAP7-AS1 expression in promoting the development of lung cancer. METHODS: Samples of 120 lung cancer and corresponding paracancerous tissues were collected. LncRNA microarrays were used to analyze differentially expressed lncRNAs. THAP7-AS1 levels were detected in lung cancer, adjacent normal tissues and lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of THAP7-AS1 in lung cancer and the relationship between THAP7-AS1 expression and survival rate and clinicopathological parameters were analyzed. Bioinformatics analysis, methylated RNA immunoprecipitation (meRIP), RNA pull-down and RNA-immunoprecipitation (RIP) assay were used to investigate the molecular regulation mechanism of THAP7-AS1. Cell proliferation, migration, invasion and tumorigenesis of SPC-A-1 and NCI-H1299 cells were determined by MTS, colony-formation, scratch, Transwell and xenotransplantation in vivo, respectively. Expression levels of phosphoinositide 3-kinase/protein kenase B (PI3K/AKT) signal pathway related protein were detected by Western blot. RESULTS: Expression levels of THAP7-AS1 were higher in lung cancer tissues and cell lines (P<0.05). THAP7-AS1 has certain diagnostic value in lung cancer [area under the curve (AUC)=0.737], and its expression associated with overall survival rate, tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). METTL3-mediated m6A modification enhanced THAP7-AS1 expression. The cell proliferation, migration, invasion and the volume and mass of transplanted tumor were all higher in the THAP7-AS1 group compared with the NC group and sh-NC group of SPC-A-1 and NCI-H1299 cells, while the cell proliferation, migration and invasion were lower in the sh-THAP7-AS1 group (P<0.05). THAP7-AS1 binds specifically to Cullin 4B (CUL4B). The cell proliferation, migration, invasion, and expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD), phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) were higher in the THAP7-AS1 group compared with the Vector group of SPC-A-1 and NCI-H1299 cells (P<0.05). CONCLUSIONS LncRNA THAP7-AS1 is stably expressed through m6A modification mediated by METTL3, and combines with CUL4B to activate PI3K/AKT signal pathway, which promotes the occurrence and development of lung cancer.
Humans ; Lung Neoplasms/pathology* ; RNA, Long Noncoding/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Up-Regulation ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Methyltransferases/metabolism* ; Cullin Proteins/genetics*

OBJECTIVE To explore the self precipitation source of Erhuang powder, determine the content of related components and its efficacy on HeLa cells. METHODS Bifurcation study to identify the main compatibility of precipitating. The self precipitation, supernatant and extract of Erhuang powder were analyzed by UHPLC-Q-Exactive MS. The main compounds in Coptidis Rhizoma and Catechu, catechin, epicatechin, epicberberine, coptisine, berberine and palmatine were selected as controls. A analysis method of UHPLC for self precipitation, supernatant and extract of Erhuang powder was established and the related components were quantitatively determined. The effects of self precipitation, supernatant and extract on HeLa cells were evaluated by MTT method and flow cytometry. RESULTS A slight flocculation precipitate appeared when the decoction of Erhuang powder was mixed in pairs, while a large amount of flocculation appeared when the decoction of Coptidis Rhizoma and Catechu water was mixed. The self precipitation, supernatant and extract samples contained 39 compounds, which were mainly alkaloids and phenolic acids. The contents of catechin and berberine in the 6 index components were mostly, which accounted for 73.56% of the total content of the index components in self precipitation and 61.89% of the total content of the index components in extract. Inhibition effect on HeLa cells: extract ≈ self precipitation > supernatant, and inducing apoptosis: self precipitate ≈ extract, supernatant had no apoptosis-inducing effect. CONCLUSION Coptidis Rhizoma-Catechu is the main compatible formula for precipitation formation. The self precipitation and extracts of Erhuang powder are mainly alkaloids and phenolic acids, among which berberine and catechin are high in content and can be used as representative components. The effect of self-precipitation and extract on HeLa cells was better than that of supernatant. This basically indicates that the self precipitation components and pharmacological effects of Erhuang powder are similar to those of the extract.