Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Objective: To explore the association between physical activity, anxiety symptoms and academic performance among junior high school students, so as to provide data support for optimizing school physical education and health work and formulating physical activity guidelines. Methods: From September to December 2022, a convenience cluster sampling method was used to survey 2 800 junior high school students in a middle school from Anqing City, Anhui Province. Data were collected on the students anxiety symptoms, academic performance, 24 hour physical activity [moderate to vigorous intensity physical activity(MVPA), light intensity physical activity(LPA), sedentary behavior(SB), and sleep(SLP) duration] as well as demographic characteristics. Compositional data analysis was used to explore the associations between 24 hour physical activity, anxiety symptoms and academic performance among junior high school students, and to predict the optimal time use combination pattern. Results: Among the junior high school students, 16.0% (447 students) reported anxiety symptoms, and 42.0% (1 175 students) achieved excellent or good academic performance. Compositional data analysis showed that increased SLP duration was associated with both reduced anxiety symptoms ( β =-0.18) and decreased academic performance ( β =-0.03) among junior high school students; increased MVPA duration was correlated with fewer anxiety symptoms ( β =-0.02) and lower academic performance ( β =-0.13); in contrast, increased SB duration was linked to more anxiety symptoms ( β =0.09) and higher academic performance ( β =0.09) (all P <0.01). LPA duration exhibited a non linear relationship with anxiety symptoms and academic performance in junior high school students (all P >0.05). The time use combination pattern corresponding to the lowest anxiety symptoms and highest academic performance (top 5%) in adolescents was 611 (520-640) minutes of SLP, 258 (230-320) minutes of SB, 454 (280-610) minutes of LPA, and 117 (20-200) minutes of MVPA per day. Conclusions The 24 hour physical activity of junior high school students is associated with anxiety symptoms and academic performance. Therefore, it is recommended to increase the time spent on SB, MVPA, and LPA for junior high school students, while reducing SB.

OBJECTIVE To explore the mechanism Baitouweng Decoction on mice with vulvovaginal candidiasis(VVC)based on phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)-hypoxia-inducible factor-1α(HIF-1α)pathway.METHODS Female SPF-grade Kunming mice were injected subcutaneously with estradiol benzoate and vaginally inoculated with Candida albicans suspension to establish a VVC mouse model.The mice with successful modeling were randomly divided into model group,high-,me-dium-,and low-dose Baitouweng Decoction groups(23.4,11.7,and 5.85 g·kg-1),and fluconazole group(0.02 g·kg-1),with 20 mice in each group.Another 20 mice were injected with estradiol benzoate as control group.Treatment started the day after success-ful model establishment and continued for 14 days.Two hours after the last administration,the number of neutrophils in vaginal lavage fluid was examined with Papanicolaou stain.The HE staining method was used to observe the morphology of vaginal tissue.ELISA was used to measure the levels of nicotinamide adenine dinucleo-tide phosphate oxidase 2(NOX2),reactive oxygen species(ROS),su-peroxide dismutase(SOD),malondialdehyde(MDA)in the vaginal tissues.The mRNA expression levels of PI3K,AKT and HIF-1α were detected using qPCR.Western blot was employed to evaluate the protein expression of p-PI3K,PI3K,p-AKT,AKT,and HIF-1α in vaginal tissue.RESULTS Compared to the control group,the model group exhibited a significant increase in neutrophils in va-ginal lavage fluid(P<0.001);the vaginal mucosal layer was severely desquamated and a large number of inflammatory cells infiltrated.Additionally,there was an elevation in NOX2,ROS,and MDA levels in vaginal tissue(P<0.001),while SOD content decreased(P<0.001).Furthermore,the mRNA expression of PI3K,AKT and HIF-1α was reduced along with decreased protein ex-pression of p-PI3K/PI3K,p-AKT/AKT,and HIF-1α(P<0.001).In comparison to the model group,both high-dose and medi-um-dose groups treated with Baitouweng Decoction demonstrated a significant decrease in neutrophil count in lavage fluid(P<0.01,P<0.001);the condition of the vaginal mucosa improved to varying degrees.Moreover,the levels of ROS and MDA in vaginal tissue were reduced(P<0.05,P<0.01,P<0.001),the activity of NOX2 was decreased(P<0.01,P<0.001),and the activity of SOD was increased(P<0.01,P<0.001).The high-dose group showed that,the mRNA expression of PI3K,AKT,and HIF-1α in vaginal tissue was increased(P<0.001),the ratios of p-PI3K/PI3K and p-AKT/AKT,and the protein expression of HIF-1α were increased(P<0.001).CONCLUSION Baitouweng Decoction has a therapeutic effect on VVC,and its mechanism of action may be related to the PI3K/AKT-HIF-1α signal pathway.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Objective: To explore the association between light intensity physical activity (LPA) and sedentary behavior (SB) with body composition, so as to provide data references for improving adolescent physical health. Methods: From August 2020 to January 2021, general information of 694 students in grade one of a high school in Foshan City was collected, and the 24 hour activity behavior and body composition of the students were measured objectively by triaxial accelerometer and bioelectrical impedance tester. Dual component multivariate regression and dual compositional isotemporal substitution model were used to explore the relationship between LPA and SB and body composition. Results: LPA was associated with lower fat relative dominance (FRD) (male weekends FRD=-21.44%, female weekly FRD=-17.83%, weekdays FRD=-18.27%, P <0.05), and LPA was also associated with higher muscle relative dominance (MRD) and bone relative dominance (BRD) (male weekends MRD=12.78%, BRD= 12.87 %; female weekly MRD=11.64%, BRD=9.01%; female weekdays MRD=12.02%, BRD=9.23%, P <0.05). Replacing sedentary behavior (SB) with 10 minutes of LPA could reduce fat proportion [male:weekly -0.15(-0.26--0.04), weekdays -0.12 (-0.22--0.02); female:weekly -0.18(-0.27--0.08), weekdays -0.16(-0.25--0.07)) and increase muscle proportion (male:weekly 0.14(0.03-0.24), weekdays 0.11(0.02-0.21); female:weekly 0.17(0.07-0.26), weekdays 0.15(0.07-0.24)]. Conclusion Interrupting continuous SB with LPA can serve as an intervention measure to promote physical health and fitness in adolescents. School should encourage students to engage in frequent LPA during breaks and after school activities, while avoiding prolonged SB.

Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.
Humans ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; MicroRNAs/metabolism* ; Glioma/genetics* ; Genes, Tumor Suppressor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

Objective:To explore the value of using the mean gamma index (GI) in targer area receiving 50% prescribed dose as reference in VMAT planned dose verification through model-based dose calculation and measurement-based dose reconstruction.Methods:Based on Compass dose verificantion system, the VMAT plans for 70 patients were validated using two method. The mean GI and passing rate in target area receiving 50% of prescribed dose area for each validation plan were obtained to evaluate its application value in dose validation. First, plan information obtained by TPS calculation was input into the Compass system for performing independent dose calculation based on the accelerator data model, and obtain a three-dimensional dose based on the independent model calculation. The planned fluence measured for each patient′s treatment plan on the accelerator was reconstructed through the Compass system to obtain a three-dimensional dose based on measurement reconstruction. The three-dimensional dose obtained by the two method were compared with the three-dimensional dose calculated by TPS.Results:Combined with the gamma criteria of 3%/3 mm in the error setting condition of GI analysis, the mean GI in the area receiving 50% of prescribed dose was evaluated. GI≤0.4 was classified as PASS, 0.4 < GI ≤ 0.6 as being clinically acceptable, and GI > 0.6 as FAIL. The VMAT planned dose verification for 70 patients showed that the model-based independent calculation was in a better agreement with the TPS calculation. The GI values were all < 0.6: GI≤0.4 for 67 patients and 0.4 90% for 88 patients and < 90% for other 2, all meeting the requirements of clinical dose verification. The model-based independent dose verification is better than the measurement-based reconstructed dose verificantion, and the difference is statistically significant ( t=15.20, 10.71, P < 0.05). Conclusions:The mean GI in target area receiving 50% of prescribed dose can be used as a reference to judge the operatability of clinical plan in clinical dose verification. The mean GI value, in combination with the comprehensive result of gamma passing rate, is more convincing to evaluate dose verification. A combination of model-based dose verification, despite time-saving and labor-saving, and the measurement-based dose verification could become a reliable dose verification method for clinical application.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.