Objective: To explore the efficacy of a novel injectable hydrogel (GelMA/P11/IL4@LIP) loaded with P11 bacteriophages and interleukin-4 (IL-4) liposomes (LIP) in preventing relapse after maxillary expansion in mice, providing experimental evidence for its clinical application. Methods: This study was approved by the experimental animal ethics committee of our hospital. First, 15 7-week-old C57BL/6 mice were used to establish a maxillary expansion model and divided into 5 groups (3 mice in each group): a control group, post expansion day 3 group (PED3 group), post expansion day 7 group (PED7 group), retention for 14 days group (RET group), and relapse for 7 days group (REL group). The mice in each group were sacrificed at their designated time points (day 0, 3, 7, 21, 28), and their maxilla and anterior cranial regions were collected. Bone parameters and the inter-crestal distance (ICD) of maxillary incisor mesial alveolar ridge were measured using micro-computed tomography (micro-CT). Histological staining was performed to evaluate bone formation and resorption, while immunohistochemistry (IHC) was performed for macrophage markers (CD86 and CD206), mesenchymal stem cell markers (glioma-associated oncogene homolog 1 [Gli1]), and osteogenic markers (Runt-related transcription factor 2 [Runx2] and Osterix [OSX]). Next, GelMA/P11/IL4@LIP was synthesized and administered to mouse models of maxillary expansion. A total of 24 7-week-old C57BL/6 mice were divided into 4 groups (6 mice in each group): a blank control group, GelMA group, GelMA/P11 group, and GelMA/P11/IL4@LIP group. All mice underwent palatal expansion. On PED7, the expanders of all 24 mice were cemented with resin to initiate the 14-day retention period. On day 1 of the retention phase, the mice in each group received injections of saline, GelMA, GelMA/P11, or GelMA/P11/IL4@LIP at the midpalatal suture. After the 14-day retention period, three mice in each group were randomly selected and sacrificed, while the other three had their expanders removed and underwent a 7-day relapse before being sacrificed on day 28 (REL). Micro-CT, histological staining, and IHC were performed to evaluate the preventive effect of GelMA/P11/IL4@LIP on post-expansion relapse. Results: The mice maxillary expansion model exhibited a decreased ICD at REL compared to RET in micro-CT analysis (P = 0.008). IHC analysis demonstrated prolonged M1 macrophage infiltration, scarce Gli1+ mesenchymal stem cells, and insufficient expression of osteogenic markers (RUNX2 and OSX) (P < 0.001). Compared to the blank control and GelMA groups, GelMA/P11/IL4@LIP hydrogel injection in the midpalatal suture led to increased ICD at REL, promoted the timely M2 polarization of macrophages, recruited Gli1+ mesenchymal stem cells, and upregulated the expression of RUNX2 and OSX (P < 0.05). Conclusion The mechanism of relapse after maxillary expansion involves the persistent infiltration of M1 macrophages, as well as the inadequate recruitment and insufficient osteogenic differentiation of MSCs in the midpalatal suture. The GelMA/P11/IL4@LIP composite enhanced orofacial mesenchymal stem cell recruitment and promoted the M2 polarization of macrophages, thereby enhancing osteogenesis in the midpalatal suture and preventing post-expansion relapse.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.

Objective:To investigate the clinicopathological characteristics and prognostic influencing factors in young breast cancer patients.Methods:A retrospective case series study was conducted. The clinical data of 408 young patients with breast cancer in the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2020 were retrospectively analyzed. The clinical characteristics and prognostic influencing factors of patients were observed. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-free survival (DFS) of patients. Univariate analysis of prognostic factors was conducted by using the log-rank test, and multivariate analysis was performed by using Cox proportional risk model.Results:The median age [ M ( Q1, Q3)] of 408 young female patients with breast cancer was 36 (33, 39) years; the 5-year OS and 5-year DFS rates were 89.9%, 84.0% of 387 breast cancer patients in early and middle stage (except for stage Ⅳ). There were statistically significant differences in the 5-year OS and 5-year DFS rates (excluding stage Ⅳ of DFS) of patients with different clinical staging and molecular subtypes (all P < 0.05). The differences were statistically significant in the 5-year DFS rate of patients with different pathological types and histological grades (all P < 0.05). There were no statistically significant differences in the 5-year OS and DFS rates between the patients receiving breast-conserving surgery or mastectomy (all P > 0.05). The results of multivariate Cox regression analysis indicated that clinical staging ( HR = 3.121, 95% CI: 2.301-4.233, P < 0.001) and molecular classification ( HR = 1.441, 95% CI: 1.126-1.845, P = 0.004) were independent prognostic factors for OS. Additionally, clinical staging ( HR = 3.001, 95% CI: 2.174-4.141, P < 0.001) was identified as an independent prognostic factor for DFS. Conclusions:The prognosis of young breast cancer patients is closely related to clinical staging and molecular subtype. The later the clinical stage is, the poorer prognosis is. Luminal-type breast cancer has a better prognosis than other subtypes. For early-stage breast cancer patients who meet the criteria for breast-conserving surgery, breast-conserving surgery is the first-choice alternative.

Objective:To explore the value of cardiac magnetic resonance imaging (CMR) derived left ventricular late gadolinium enhancement (LV LGE) for the primary prevention of malignant ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.Methods:This was a single-center retrospective study. Consecutive ARVC patients who underwent CMR at Fuwai Hospital between January 2016 and September 2020, with no history of malignant ventricular arrhythmias at diagnosis, were enrolled. Clinical data and CMR characteristics were collected. The primary endpoint was defined as new-onset malignant ventricular arrhythmias related events, including sustained ventricular tachycardia, ventricular fibrillation/flutter, sudden cardiac death, cardiac arrest, and appropriate implantable cardioverter-defibrillator discharge. Follow-up via telephone interviews and medical records was conducted to confirm endpoint occurrences, and patients were categorized into event-free and event groups based on endpoint status. Univariable and multivariable Cox regression analysis were performed to identify independent risk factors for malignant ventricular arrhythmias in ARVC patients. Subgroup analyses were conducted based on the ARVC 5-year risk score (cutoff: 25%) and the median value of LV LGE percentage (cutoff: 13%). Kaplan-Meier curves were plotted, and log-rank tests were used to compare the difference in the incidence of primary endpoint events between subgroups. Receiver operating characteristic curves and likelihood ratio test were used to evaluate the incremental prognostic value of LV LGE percentage beyond the ARVC 5-year risk score.Results:A total of 172 ARVC patients were enrolled, aged (39.0±16.6) years, including 73 females (42.4%). During a follow-up of 53.1 (25.4, 76.9) months, 51 patients (29.7%) experienced malignant ventricular arrhythmias related events, including 3 cases of sudden cardiac death, 1 cardiac arrest, 33 sustained ventricular tachycardia and 14 appropriate implantable cardioverter-defibrillator discharges. Multivariable Cox regression analysis indicated that the ARVC 5-year risk score ( HR=1.028, 95% CI 1.015-1.041, P<0.001) and LV LGE percentage ( HR=1.059, 95% CI 1.032-1.087, P<0.001) were independent risk factors of the primary endpoint events. Kaplan-Meier analysis using composite stratification (ARVC 5-year risk score cutoff: 25%; LV LGE percentage cutoff: 13%) demonstrated that patients with both high risk scores (≥25%) and extensive LV LGE (≥13%) had the highest risk of primary endpoint events. Notably, among patients with ARVC 5-year risk scores <25%, those with LV LGE≥13% had a higher incidence of primary endpoint events than those without (log-rank P=0.037). The composite prediction model combining the 5-year risk score and left ventricular LGE percentage demonstrated significantly improved predictive performance (area under the curve ( AUC)=0.82, 95% CI 0.75-0.90; likelihood ratio test all P<0.001) compared to single-variable models (left ventricular LGE percentage alone: AUC=0.71, 95% CI 0.63-0.82, P=0.01; 5-year risk score alone: AUC=0.71, 95% CI 0.62-0.81, P=0.02). Conclusion:LV LGE percentage independently predict new-onset malignant ventricular arrhythmias in ARVC patients and provided incremental prognostic value based on the existing ARVC 5-year risk score.

ObjectiveTo study the mechanism of Shexiang Tongxin Dripping pills-containing serum （STDP） in ameliorating angiotensinⅡ （AngⅡ）-induced cell phenotype transformation， proliferation， migration， and dysfunction of vascular smooth muscle cells. MethodsAn AngⅡ-induced proliferation and migration model of vascular smooth muscle cells was established. The cells were treated with STDP at 5%， 10%， and 20% for 24 h. The immunofluorescence assay was employed to detect the expression of α smooth muscle actin （α-SMA） and matrix metalloproteinase-2 （MMP-2）. The cell-counting kit-8 （CCK-8） assay and 5-ethynyl-2'-deoxyuridine （EdU） staining were employed to detect the proliferation of vascular smooth muscle cells， and the scratch assay was employed to detect the migration of the cells. Western blot was employed to determine the expression levels of pathway proteins such as angiotensin-converting enzyme 2 （ACE2）， angiotensin Ⅱ type 2 （AT2）， angiotensin Ⅱ type 1 （AT1）， as well as proliferation and migration proteins such as typeⅠ collagen （ColⅠ） and osteopontin （OPN）. ResultsCompared with the model group， STDP increased the expression of α-SMA， reduced the expression of MMP-2， and inhibited the proliferation and migration of vascular smooth muscle cells （P<0.05）. Furthermore， STDP up-regulated the expression levels of ACE2， AT2， and MAS1， while down-regulating the expression level of AT1， PCNA， ColⅠ， MMP-9， Rock1， Rock2， and SRF （P<0.05）. Compared with the STDP group， the ACE2 inhibitor reversed the regulatory effects of STDP. ConclusionSTDP inhibits the phenotype transformation， proliferation， and migration of vascular smooth muscle cells and regulates the expression of cell proliferation and migration-related proteins to ameliorate the dysfunction of vascular smooth muscle cells. It exerts the effects by up-regulating the expression of proteins in the ACE2-AT2/MAS pathway and down-regulating the expression of proteins in the AT1-Rock signaling pathway.

Objective:To explore the prognostic factors of patients with AML1::ETO-positive acute myeloid leukemia (AML).Methods:A retrospective cohort study was conducted. The clinical data of 42 AML1::ETO-positive AML patients diagnosed in the General Hospital of Ningxia Medical University from November 2012 to December 2023 were collected. The general clinical characteristics and short-term efficacy of patients were summarized, and the Kaplan-Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of stratified patients based on factors such as age, gender, blood cell count, immunophenotype, treatment plan, and efficacy, and the log-rank test was used for inter-group comparison. Cox proportional hazards model was used for univariate and multivariate analyses on OS and RFS.Results:Among the 42 patients, there were 22 males (52.4%) and 20 females (47.6%), with a median age of 35 years, ranged from 14 to 66 years. The common initial symptoms included fatigue, fever and bleeding. The proportions of patients with CD19 or CD56 positivity were both 54.8% (23/42). Twenty-two cases (52.4%) received IA (idarubicin+cytarabine) regimen, 8 cases (19.1%) received HAA (homoharringtonine+cytarabine+aclarubicin) regimen, and 12 cases (28.6%) received induction chemotherapy with other regimens. Seven patients (16.7%) received hematopoietic stem cell transplantation (HSCT) during subsequent treatment. After one course of induction therapy, 29 cases (69.1%) achieved complete remission (CR). The proportions of patients in the CR group with initial platelet count > 10×10 9/L [86.2% (25/29) vs. 53.8% (7/13)], CD19 positivity [65.5% (19/29) vs. 30.8% (4/13)], CD56 negativity [58.6% (17/29) vs. 15.4% (2/13)], CD34 positivity [96.7% (28/29) vs. 76.9% (10/13)], and IA regimen treatment [58.6% (17/29) vs. 38.5% (5/13)] were higher than those in the non-CR group, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in the proportions of patients stratified by gender, age, hemoglobin, chromosomal karyotype, and with or without c-kit mutation (all P > 0.05). The median follow-up time was 19.5 months, ranged from 0.9 to 133.0 months. Kaplan-Meier analysis showed that patients with initial platelet count > 10×10 9/L, CD19 positivity, CD56 negativity, non-c-kit mutation, CR after one course of treatment, and subsequent HSCT had good OS and RFS (all P < 0.05). Multivariate Cox regression analysis showed that platelet count (> 10×10 9/L vs. ≤ 10×10 9/L, HR = 0.046, 95% CI: 0.007-0.314, P = 0.002), CD19 expression (positivity vs. negativity, HR = 0.069, 95% CI: 0.010-0.495, P = 0.008), CD56 expression (positivity vs. negativity, HR = 6.478, 95% CI: 1.178-35.631, P = 0.032), CD34 expression (positivity vs. negativity, HR = 38.300, 95% CI: 2.061-711.647, P = 0.014) and CR after one course of treatment (yes vs. no, HR = 0.076, 95% CI: 0.011-0.518, P = 0.008) were independent influencing factors for OS in AML1::ETO-positive AML patients. Platelet count (> 10×10 9/L vs. ≤ 10×10 9/L, HR = 0.101, 95% CI: 0.019-0.540, P = 0.007), CD19 expression (positivity vs. negativity, HR = 0.056, 95% CI: 0.007-0.462, P = 0.007) and CD56 expression (positivity vs. negativity, HR = 7.287, 95% CI: 1.096-48.457, P = 0.040) were independent influencing factors for RFS in AML1:: ETO-positive AML patients. Conclusions:Platelet count > 10×10 9/L and CD19 positivity may indicate a good prognosis for AML patients with AML1::ETO fusion gene, while CD56 positivity may indicate a poor prognosis.

BACKGROUND: Circadian syndrome (CircS) may be closely linked to lifestyle, psychological, and occupational factors, but evidence is lacking. This study aimed to explore complex associations between lifestyle, psychological and occupational factors and CircS among employed people in southwestern China. METHODS: In this study, network analysis was used to identify complex associations between lifestyle, psychological and occupational factors and CircS in employed people from the Chinese Cohort of Working Adults (CCWA). The centrality of each variable was estimated by strength centrality index, which was calculated by the sum of edge weights connected to the variable. Bridge in the network was identified as the variables in the top 80 th percentile of overall bridge strength, which was defined as the most strongly connected variables across lifestyle, psychological and occupational factors and CircS. The differences were assessed in network structures between subgroups divided by the median score of the variable with the strongest bridge strengthen. RESULTS: Among 31,105 participants from CCWA, 5213 (16.76%) had CircS. In the constructed network, anxiety (edge weights: 0.28), smoking (edge weights: 0.15), drinking (edge weights: 0.10), perceived noise at work (edge weights: 0.08), and implicit health attitude (edge weights: -0.02) were directly related to CircS, with 83.31% of the variance for CircS explained by these neighboring factors. Anxiety was the most central variable (strength centrality: 1.20) in the network and the strongest bridge (bridge strength: 0.84) connecting all domains of variables. A stronger association between anxiety and CircS was observed in the network of participants with more severe anxiety (edge weight: 0.23) than those with less severe anxiety (edge weight: 0.03). CONCLUSION Anxiety had the strongest association with CircS and was the central factor with the highest strength centrality, also the bridge with the highest bridge strength in the network.
Humans ; Male ; Female ; Adult ; China ; Middle Aged ; Life Style ; Chronobiology Disorders/epidemiology*