Objective: To identify the stakeholders of prevention and control of obesity among middle school students and analyze their motivations and interest demands for participation, in order to provide constructive recommendations for facilitating their effective engagement of stakeholders in prevention and control of obesity among middle school students. Methods: Stakeholders and their types were identified through a combination of literature analysis and consultation with 17 experts in children and adolescents for prevention and control of obesity. From December 2023 to January 2024, by applying convenience sampling, face to face semi structured interviews were conducted with 11 individuals engaged in prevention and control of obesity for middle school students and focus group interviews were conducted with 48 students and parents. Thematic analysis was employed to obtain motivations and interest demands for stakeholder involvement in prevention and control of obesity. Results: A total of 29 subcategories within 7 major categories of stakeholders were identified, including government and relevant functional departments, non profit organizations and communities, forprofit organizations and individuals, schools, professional and technical personnel, families and individuals, and scientific research institutions, with 28 subcategories being confirmed stakeholders. Among these stakeholders, there were 3 types of cooperative relationships:management, cooperation, and service. There were some factors hindering cooperation among stakeholders including imperfections in specialized policies and lack of long term cooperative mechanisms, flaws and interest conflicts in the evaluation system, insufficiency of material resources, and poor health values. In response to these challenges, interviewees proposed to convene a working group for the prevention and control of adolescent obesity. They also suggested making a contract of responsibility, strengthening supervision over for profit organizations, enhancing advocating efforts for prevention and control of obesity, and increasing financial support. Conclusions The prevention and control of obesity for middle school students can be facilitated by forming a collaborative alliance based on the roles and relationships of stakeholders identified in the present study. Perceived conflicts of interest among stakeholders can be reconciled by employing strategies of interest integration, goal alignment, and spiritual integration, to enhance the feasibility, participation and sustainability of obesity intervention.

OBJECTIVE To explore the effectiveness, potential mechanism and compatibility characteristics of efficacy groups of Dunhuang medical prescription Daxiefei decoction in preventing and treating pneumonia based on chemical bioinformatics method. METHODS To study the effect of Daxiefei decoction freeze-dried powder solution on the proliferation activity of lung epithelial cells through cell experiments. Daxiefei decoction was divided into three groups: clearing away heat group, resolving phlegm group, and nourishing Yin group according to its efficacy characteristics. The chemical components of Daxiefei decoction were obtained by TCMSP database and literature search, and the targets were predicted in Swiss Target Prediction database. Pneumonia disease targets were obtained by DrugBank, TTD, Genecards and DisGeNET databases. STRING database and Cytoscape were used to construct the intersection target interaction network and "drug-component-target- pathway" network and DAVID database was used for KEGG pathway enrichment analysis. The network was used to analyze the scientific connotation of the compatibility of efficacy groups. Furthermore, molecular docking was used to evaluate the target-compound affinity and molecular dynamics was used to explore the dynamic molecular mechanism. RESULTS Cell experiments showed that Daxiefei decoction can maintain the proliferation of lung epithelial cells, reverse the decrease of mitochondrial activity induced by LPS and reduce apoptosis. Complex network analysis showed that the pathways enriched by the three functional groups contained in Daxiefei decoction were mainly distributed in two modules: inflammation regulation and reducing airway mucus hypersecretion. Each module was connected by a common target gene and had its own focus. The results of molecular docking showed that the components quercetin, baicalein, isorhamnetin etc. might be the effective multi-target components of Daxiefei decoction. SRC, EGFR, PPARA etc. had good affinity with each potential active component, which might be a potential target of Daxiefei decoction for preventing and treating pneumonia. Molecular dynamics simulation showed that the potential active component quercetin formed stable intermolecular interactions with SRC. CONCLUSION This study initially reveal the material basis and molecular mechanism of Daxiefei decoction in the prevention and treatment of pneumonia. It also explores the scientific connotation of Daxiefei decoction in the prevention and treatment of pneumonia with different efficacy groups, and its modern development and clinical application provide chemical bioinformatics basis.

Objective Based on the process theory of stress effect,the structural equation model of the influencing factors of self-regulatory fatigue in maintenance hemodialysis patients is constructed,which provides theoretical bases and references for the formulation of intervention programs to relieve self-regulatory fatigue in patients.Method A total of 420 maintenance hemodialysis patients were surveyed using General Information Questionnaire,Self-Regulatory Fatigue Scale,Dialysis Symptom Index,Life Orientation Test-Revised,Perceived Social Support Scale,Brief Illness Perception Questionnaire and Medical Coping Styles Questionnaire.Results Total score of self-regulatory fatigue in maintenance hemodialysis patients was(49.52±10.93),and self-regulatory fatigue showed significant positive correlation with symptom distress,the illness perception,avoidance coping style,yieldly coping(r=0.476,0.428,0.303,0.611,all P＜0.01);self-regulatory fatigue showed significant negative correlation with perceived social support and dispositional optimism(r=-0.410,-0.652,all P＜0.01);it showed no significant correlation with facing coping(r=-0.032,P＞0.05).The Bootstrap analysis revealed that the mediation effect of yielding coping,dispositional optimism,perceived social support,and illness perception between symptom distress and self-regulatory fatigue was significant(95％CI:0.027～0.203).The overall effect of symptom distress on self-regulatory fatigue was(P＜0.001,95％CI:0.576～0.751);the direct effect was(P＜0.001,95％CI:0.170～0.357);the indirect effect was(P＜0.001,95％CI:0.332～0.485);the mediation effect accounted for 61.1％of the total effect value.Conclusion Maintenance hemodialysis patients have a high degree of self-regulatory fatigue,which needs to be further improved.Medical staff should timely identify and evaluate the symptom distress of patients,focus on guiding patients to adjust optimistic disease,provide patients with psychological guidance and stress coping strategies,reduce the negative coping behavior tendency,guide the patients correctly perceive support and care in social relations,help patients set up the correct disease cognition,thus reducing the patient's self-regulatory fatigue.

Objective To explore the trend in self-management efficacy and exercise compliance among patients within 6 months after radical resection of lung cancer and analyse the predictive correlation between the factors to provide references for improvement of exercise compliance in patients after lung cancer surgery.Methods Convenience sampling was used to select patients who had surgery of radical resection of lung cancer for the first time in the departments of thoracic surgery of two Grade IIIA hospitals in Nanchong between December 2022 and May 2023.The Chinese-version strategies used by people to promote health(C-SUPPH)and exercise compliance scale were employed to assess the self-management efficacy and patient exercise compliance at four time points:1 day before discharge(T1)and 1 month(T2),3 months(T3)and 6 months(T4)after surgery.A cross-lagged model was constructed to analyse the causal correlation between self-management efficacy and exercise compliance.Results Within 6 months after surgery,both of self-management efficacy and exercise compliance in the patients after radical resection of lung cancer were seen initially increased and then decreased(P<0.05).The cross-lagged model revealed that self-management efficacy and exercise compliance during the early postoperative period(TI-T2)exhibited reciprocal causation(β=0.254,P=0.003;β=0.332,P=0.007).Between T2 and T3,higher self-management efficacy positively predicted an increased exercise compliance(β=0.286,P<0.001).However,during T3 and T4,no predictive relationship was observed between the indicators(P>0.05).Conclusion The self management efficacy of patients after lung cancer sugery is at middle level and their exercise compliance is at low level.This study indicates that the initial levels of self-management efficacy and exercise compliance among patients after radical resection of lung cancer do not necessarily reflect a long-term trend.The predictive correlation between the two factors also varies over the time.Healthcare providers should consider the dynamic changes and individual differences across different stages after surgery,and implement timely and targeted intervention.

Clinical data of 166 children with Meckel's diverticulum, who were treated with laparoscopic surgery in our center from January 2015 to January 2023, were retrospectively analyzed, including 69 cases receiving enhanced recovery after surgery (ERAS group) and 97 cases with traditional perioperative care (control group). There were no significant differences in age ( t=1.391), gender ( χ2=1.067), body weight ( t=1.182 ), operation time ( t=1.093), diverticulum location ( Z=0.405), surgical procedures ( χ2=0.053), and intraoperative blood loss ( t=0.394) between two groups (all P>0.05). Compared to control group, ERAS group had shorter time for indwelling gastric tube (1.1±0.7 d vs.3.8±0.8 d), earlier postoperative feeding (2.5±0.6 d vs.4.9±0.7 d), less intravenous fluid infusion (3.9±1.0 d vs. 5.3±1.1 d), shorter length of hospital stay (8.2±1.6 d vs.10.9±2.3 d), and lower hospitalization expenditure (1.8±0.2)×10 4 yuan vs. (2.1±0.3)×10 4 yuan ( t=23.289,21.718,8.505,8.379,8.769,all P<0.05). There was no significant difference in incidence of postoperative complications between two groups ( χ2=0.431, P>0.05). The study indicates that patients treated with ERAS programmed laparoscopic Meckel's diverticulum surgery is safe and effective with rapid recovery and shorter hospital stay.

Objective:To investigate the expression and clinical significance of SKA3 protein in cholangiocarcinoma, and the effect of interfering SKA3 expression in vitro on the proliferation, invasion, and migration of cholangiocarcinoma SSP-25 cells, as well as its possible mechanism.Methods:The clinicopathological data, cancer tissues, and paracancerous tissues from 172 patients with distal cholangiocarcinoma in Beijing Friendship Hospital, Capital Medical University between January 2015 and December 2020 were retrospectively collected. Immunohistochemical method was used to detect the expression level of SKA3 protein in cancer tissues and paracancerous tissues. Transfection of SKA3 small interfering RNA (siRNA) into cholangiocarcinoma SSP-25 cells was used as si-SKA3 group, and the untreated SSP-25 cells were used as the control group. Cell immunofluorescence staining and Western blot were used to detect the transfection effect; CCK-8 method and cell colony formation experiment were used to observe changes in cell proliferation; cell scratch assay was used to monitor cell invasion; Western blot was used to detect the expression of PI3K-AKT signaling pathway related proteins.Results:Among 172 patients with cholangiocarcinoma, there were 116 males and 56 females; the age of 54 cases was under 60 years, and age of 118 cases was equal to or more than 60 years. The positive rate of SKA3 protein in cholangiocarcinoma tissues was higher than that in paracancerous tissues [78.49% (135/172) vs. 13.95% (24/172)], and the difference was statistically significant ( χ2 = 42.78, P < 0.01). The positive rate of SKA3 protein in cancer tissues of cholangiocarcinoma patients with nerve invasion [84.35% (124/147) vs. 44.00% (11/25)] and lymph node metastasis [88.78% (87/98) vs. 64.86% (48/74)] was higher than that of patients without nerve invasion and without lymph node metastasis, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in the positive rate of SKA3 protein in cancer tissues of patients stratified by age, gender, tumor diameter, TNM stage, and tumor differentiation (all P > 0.05). The CCK-8 method showed that after 72 h of cultivation, the proliferation ability of SSP-25 cells in the si-SKA3 group (expressed as absorbance value at 450 nm) was lower than that in the control group (0.56±0.05 vs. 0.83±0.06), and the difference was statistically significant ( t = 3.06, P = 0.06). After 2 weeks of cultivation, the colony formation experiment showed that the number of colony formation of SSP-25 cells in the si-SKA3 group was lower than that in the control group. After 24 h of cultivation, the scratch healing rates of SSP-25 cells in the si-SKA3 group and the control group were (31±6) % and (72±5)%, respectively, and the difference was statistically significant ( t = 5.63, P = 0.013).Western blot analysis showed that the relative expression levels of p-PI3K and p-AKT proteins in the PI3K-AKT signaling pathway were lower than those in the control group, and the difference was statistically significant (all P < 0.05). Conclusions:SKA3 protein is highly expressed in cholangiocarcinoma tissues, and may related to nerve invasion and lymph node metastasis. Interfering SKA3 expression can inhibit the proliferation and invasion of cholangiocarcinoma SSP-25 cells, and its mechanism may be related to the inhibition of the PI3K-AKT signaling pathway.

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl₂ at designed doses (0, 0.5, 1.0, and 1.5 μmol·L⁻¹). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L⁻¹ dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.

Objective:To investigate the expression and clinical significance of decoy receptor 3 (DcR3) and its signal pathway-related molecules in PBMCs of patients with ankylosing spondylitis (AS).Methods:Peripheral blood samples, clinical data and laboratory test results were collected from 100 patients with ankylosing spondylitis [50 patients with AS activity (ASA), 50 patients with AS stability (ASS)], 30 patients with osteoarthritis and 30 patients with gouty arthritis (as disease control group), and 60 healthy controls (HC). The mRNA expression levels of DcR3 and its signal pathway related genes (DR3, TL1A, Fas, FasL, LIGHT, LIGHTR, LTβR) were measured by real-time fluorescence quantitative polymerase chain reaction. Measurement data among the three groups in normal distribution were analyzed by t test or one-way analysis of variance, pairwise comparisons using LSD- t test, non-normal distribution data were analyzed by Mann-Whitney test or Kruskal-Wallis H test, χ2 test was used for correlation analysis of categorical variables. Correlation analysis between variables were analyzed using Spearman correlation analysis. Results:① By comparing the AS group, disease control group and HC group, the expression levels of DcR3 mRNA and DR3 mRNA in the AS group were lower than those in disease control group and HC group, and DcR3 mRNA and DR3 mRNA in disease control group were lower than those in the HC group {DcR3mRNA: [6.21 (3.89, 10.70)]×10 -4vs [9.51 (5.89, 16.65)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=55.28, P<0.001; DR3 mRNA: [41.05 (24.09, 66.95)]×10 -4vs [58.28 (28.41, 94.38)]×10 -4vs [94.79 (54.07, 144.51)]×10 -4, H=37.10, P<0.001}. The expression level of TL1A mRNA in the AS group was higher than that in disease control group {[14.71(4.91, 42.22)]×10 -4vs [4.00(1.07, 16.60)]×10 -4vs [7.70 (3.52, 27.83)]×10 -4, H=17.71, P<0.001}; The expression level of Fas mRNA in AS group and disease control group was lower than that in HC group {[20.99(4.63, 62.89)]×10 -4vs [23.97(15.82, 38.99)]×10 -4vs [78.45 (27.32, 146.46)]×10 -4, H=31.17, P<0.001}. The expression level of FasL mRNA in AS group was higher than that in disease control group and HC group {[42.87(6.57, 91.21)]×10 -4vs [5.45(2.83, 10.32)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=46.42, P<0.001}. The expression level of LIGHTR mRNA in AS group was lower than that in disease control group {[52.66 (7.20, 143.21)]×10 -4vs [98.80 (53.11, 166.24)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.96, P<0.001}. There were no significant differences in LIGHT mRNA and LTβR mRNA among all groups ( H=0.86, P>0.05; H=3.18, P>0.05). ②The expression levels of DcR3 mRNA, DR3 mRNA and Fas mRNA in ASA group and ASS group were lower than those in HC group. DcR3 mRNA in ASA group was higher than that in ASS group, and DR3 mRNA in ASA group was lower than that in ASS group {DcR3 mRNA: [7.28 (4.92, 16.56)]×10 -4vs [4.59 (2.49, 7.03)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=62.63, P<0.001; DR3 mRNA: [30.93(16.18, 66.66)]×10 -4vs [47.17(29.91, 67.40)]×10 -4vs [94.79(54.07, 144.51)]×10 -4, H=41.48, P<0.001; Fas mRNA: [20.04(3.29, 62.30)]×10 -4vs [22.49(5.63, 64.79)]×10 -4vs [78.45(27.32, 146.46)]×10 -4, H=23.54, P<0.001}. The expression levels of TL1A mRNA and LTβR mRNA in the ASA group were higher than those in the ASS group and the HC group {TL1A mRNA: [32.36(10.09, 97.84)]×10 -4vs [9.98(1.29, 21.63)]×10 -4vs [7.70(3.52,27.83)]×10 -4, H=21.14, P<0.001; LTβR mRNA: [6.13(2.16,20.06)×10 -4vs [2.13(0.53,8.04)]×10 -4vs [2.72 (1.24,5.73)]×10 -4, H=12.86, P<0.001}. The expression level of FasL mRNA in the ASA group and the ASS group was higher than that in the HC group {[60.70 (8.16, 106.16)]×10 -4vs [30.14 (5.37, 78.40)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=18.99, P<0.001}. The expression level of LIGHTR mRNA in ASS group was lower than that in HC group {[49.79(10.75, 168.48)]×10 -4vs [15.92(3.27, 105.91)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.80, P<0.001]. There was no significant difference in LIGHT mRNA among all groups ( H=4.15, P>0.05). ③Spearman correlation analysis showed that DcR3 level was positively correlated with BASDAI score and hsCRP in AS patients ( r=0.52, P<0.001; r=0.35, P<0.01), and DR3 level was negatively correlated with BASDAI score, ESR and hsCRP level ( r=-0.28, P<0.001; r=-0.25, P<0.001; r=-0.31, P<0.001). TL1A was positively correlated with BASDAI score, ESR and hsCRP level ( r=0.23, P=0.046; r=0.26, P=0.015; r=0.25, P=0.017). Conclusion:DcR3 and its signal pathway-related molecules are differentially expressed in PBMCs of patients with AS, suggesting that they may participate in the occurrence and development of AS.

As an important intracellular genetic and regulatory center, the nucleus is not only a terminal effector of intracellular biochemical signals, but also has a significant impact on cell function and phenotype through direct or indirect regulation of nuclear mechanistic cues after the cell senses and responds to mechanical stimuli. The nucleus relies on chromatin-nuclear membrane-cytoskeleton infrastructure to couple signal transduction, and responds to these mechanical stimuli in the intracellular and extracellular physical microenvironments. Changes in the morphological structure of the nucleus are the most intuitive manifestation of this mechanical response cascades and are the basis for the direct response of the nucleus to mechanical stimuli. Based on such relationships of the nucleus with cell behavior and phenotype, abnormal nuclear morphological changes are widely used in clinical practice as disease diagnostic tools. This review article highlights the latest advances in how nuclear morphology responds and adapts to mechanical stimuli. Additionally, this article will shed light on the factors that mechanically regulate nuclear morphology as well as the tumor physio-pathological processes involved in nuclear morphology and the underlying mechanobiological mechanisms. It provides new insights into the mechanisms that nuclear mechanics regulates disease development and its use as a potential target for diagnosis and treatment.
Cell Nucleus ; Biophysics ; Cytoskeleton ; Phenotype ; Signal Transduction

AIM:This study aims to investigate the histopathological and ultrastructural alterations in the lung tissues of rats induced by a single intratracheal administration of bleomycin,with the objective of establishing a reliable model for future applications.METHODS:Six to eight-week-old SD rats were randomly allocated into two groups:the control group and the model group(n=12).Pulmonary fibrosis was induced in the rat models by a single intratracheal in-stillation of bleomycin(3 mg/kg),while an equivalent volume of saline was administered to the control group.The rats were executed on the 42nd day.Twelve rats remained in the control group,while nine rats remained in the model group.Lung tissue imaging was conducted using CT scans.Lung function tests were performed to assess changes in forced vital capacity(FVC)and dynamic lung compliance(Cdyn).Lung stiffness was determined through Young's modulus testing using a rheometer.The pathological structure of lung tissues was examined using both HE and Masson staining methods.Additionally,transmission electron microscopy was employed to evaluate collagen deposition in lung tissues,alveolar type Ⅱ epithelial cells,macrophages,and ultrastructural changes of the respiratory membrane.RESULTS:CT scans revealed honeycomb patterns in the lungs of model rats,along with partial bronchiectasis/bronchiectasis.In comparison to the con-trol group,the model group exhibited significantly lower FVC and Cdyn values,while lung stiffness were increased.HE and Masson staining demonstrated that rats in the model group exhibited alveolar structure destruction,alveolar septum thickening,inflammatory cell infiltration,and collagen deposition in alveolar septum.Transmission electron microscopy revealed several abnormalities in the model group:increased collagen fibers in the alveolar septa,misalignment of micro-villi in alveolar type Ⅱ epithelial cells,wrinkled nuclei with increased heterochromatin,swollen cytoplasmic mitochon-dria,fractured or haphazardly structured mitochondrion cristaes,and a significant decrease in their number(P＜0.05).Furthermore,lamellar bodies were vacuolated and reduced in number(P＜0.05),and dilated endoplasmic reticulums with degranulation were observed.There was an increase in alveolar macrophages and interstitial macrophages(P＜0.01).The respiratory membrane displayed structural disruptions and an increase in thickness(P＜0.01).CONCLUSION:Bleomycin induces decreased lung compliance,alveolar epithelial injury,alveolar septum thickening,collagen deposi-tion,and an increase in interstitial macrophages,ultimately resulting in pulmonary fibrosis in rats.