Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

Objective: To investigate the associations between childhood obesity and performance of six minute walk test (6MWT), providing evidence for exercise tolerance assessment and exercise intervention strategies for children and adolescents. Methods: From March 2021 to December 2023, a cohort study was conducted among students recruited from a primary and secondary school in Chongqing, a total of 709 valid samples were included. The 6MWT was used to assess exercise tolerance, with vital signs measured before and after the test. Anthropometric indicators, including height, weight, and waist circumference, were measured using standardized procedures. Generalized additive models (GAM) and restricted cubic spline (RCS) regression were employed to analyze the nonlinear relationships between obesity related indicators and six minute walk distance (6MWD). Results: The mean 6MWD of participants was (602.59±70.73)m. GAM showed that after adjusting for confounding factors, body mass index (BMI) and weight had non linear relationships with 6MWD [effective degrees of freedom were 1.55 and 7.13 respectively], and overweight/obesity was associated with a decrease in 6MWD ( β =-18.65) (all P <0.01). Further RCS regression analysis showed that both BMI and weight showed an "inverted U shaped" non linear relationship with 6MWD in the overall population and sex stratified subgroups; the 6MWD of females was lower than that of males, and it showed a significant downward trend with the increase of BMI or weight (all P <0.05). Conclusion Body weight and BMI in children and adolescents have an important impact on 6MWD, and obesity in children and adolescents is markedly associated with decline in exercise tolerance.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

The culture of suspended Vero cells is facing difficulties such as low cell viability and long doubling time. To investigate the main reasons for the slow growth and low viability of suspended Vero cells, this study conducted transcriptomic analysis of suspended Vero cells (Vero-XF) and adherent Vero cells (Vero-AD) to screen the differentially expressed genes (DEGs) affecting the growth of suspended cells. In addition, epidermal growth factor (EGF) was supplemented to the culture system to improve the growth of Vero-XF. The results showed that compared with the Vero-AD group, the Vero-XF group had 7 376 significant DEGs. Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the DEGs were mainly enriched in the autophagy and mitophagy pathways. Eleven DEGs were selected and verified by quantitative real-time PCR, which showed up-regulated expression of ATG9B, WIPI2, LAMP2, OPTN, Rab7a, and DEPTOR and down-regulated expression of ATG4D, being consistent with the results of transcriptomic analysis. In addition, the Vero-XF group showed significantly up-regulated expression of ATG101, ATG2A, and STX17 and insignificant change in the expression of NBR1, compared with the Vero-AD group. The protein levels of LC3 and P62 in Vero-XF and Vero-AD were determined by Western blotting, which showed up-regulated expression of LC3Ⅱ/Ⅰ and down-regulated expression of P62 in Vero-XF, indicating a higher level of autophagy. Finally, the exogenous supplementation of EGF at 10, 20, and 30 μg/L in the culture system reduced the autophagy level of Vero-XF by 22.35%, 48.15%, and 71.29%, increased the specific growth rate by 15.48%, 33.33%, and 57.14%, and decreased the apoptosis rate by 2.84%, 15.46%, and 16.23%, respectively. The results of this study preliminarily reveal that the activation of autophagy is one of the reasons for the slow growth of Vero-XF, which provides reference for the subsequent culture of suspended Vero cells.
Animals ; Vero Cells ; Autophagy/genetics* ; Chlorocebus aethiops ; Epidermal Growth Factor/pharmacology* ; Gene Expression Profiling ; Transcriptome ; Cell Survival

Objective:To investigate the pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1％DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P＜0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P＜0.05),while the viabilities of TM3 cells in other groups had no significant changes(P＞0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P＜0.05),the expression levels of PI3K protein were decreased(P＜0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P＜0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P＜0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P＜0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P＜0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P＜0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P＜0.05),and the expression levels of IFT80 mRNA(P＜0.01)and Bax protein(P＜0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P＜0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P＜0.05),while the expression level of RNF130 mRNA was increased(P＜0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P＜0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.