Objective: To investigate the molecular regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) in mechanical stress-induced inflammatory cytokine expression in human periodontal ligament cells (hPDLCs), providing a theoretical basis and potential therapeutic target for inflammatory control during orthodontic treatment. Methods: This study was approved by the Institutional Ethics Committee. Primary human periodontal ligament cells (hPDLCs) were isolated and cultured in vitro. Self-renewal capacity was confirmed via colony-forming assays, while osteogenic and adipogenic differentiation potential was evaluated via Alizarin Red S staining, alkaline phosphatase (ALP) activity assays, and Oil Red O staining. An in vitro compressive force stimulation model (1.5 g/cm2, 12 h) was established to compare inflammatory cytokine expression of hPDLCs—interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and HIF-1α—between the Control group (no mechanical stimulation) and the Force group (1.5 g/cm2, 12 h) using quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence (IF) staining. Mechanically induced HIF-1α-regulated gene expression changes were analyzed through transcriptomic sequencing. To explore pharmacological inhibition, the small-molecule HIF-1α inhibitor LW-6 was applied at varying concentrations (10 μmol/L, 30 μmol/L, 50 μmol/L) to optimize the treatment dose. Subsequently, qRT-PCR, Western blot, and IF staining were conducted to evaluate inflammatory cytokine of hPDLCs and HIF-1α expression in three groups: Control (no force), Force (1.5 g/cm2, 12 h), and Force+LW6 (1.5 g/cm2, 12 h + 30 μmol/L LW-6). Results: Primary hPDLCs demonstrated self-renewal capacity along with osteogenic and adipogenic differentiation potential. Compared to the Control group, the Force group exhibited significantly increased mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6, and TNF-α, along with enhanced fluorescence intensity of IL-1β and TNF-α. Transcriptomic analysis revealed that mechanical compressive force activated the HIF-1 signaling pathway, which subsequently mediated inflammatory responses and bone remodeling processes in hPDLCs. Furthermore, the mRNA and protein levels of HIF-1α were considerably elevated in the Force group compared to the Control group. Treatment with LW-6 (10, 30, or 50 μmol/L) effectively suppressed HIF-1α expression, with 30 μmol/L LW-6 identified as the optimal concentration for intervention. In subsequent experiments, the Force group showed significant upregulation in mRNA/protein expression of IL-1β, IL-6, and TNF-α compared to the Control group, as well as intensified HIF-1α, IL-1β, and TNF-α fluorescence signals. Conversely, the Force+LW6 group (mechanical force + 30 μmol/L LW-6) exhibited a notable reduction in inflammatory cytokine expression levels and a weakening of HIF-1α, IL-1β, and TNF-α fluorescence signals compared to the Force group. Conclusion HIF-1α potentiates mechanical stress-induced inflammatory responses in hPDLCs and may serve as a promising therapeutic target for mitigating orthodontic-associated periodontal inflammation.

The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Abstract To explore the influence of the occurrence and development of bystander behavior in cyberbullying among adolescents, the paper reviews the factors influencing bystander behavior from the perspective of social ecosystem theory at the individual level, microsystem (family and school factors), peripheral system (contextual factors), macrosystem (cultural factors) and digital environment (media factors). It is pointed out that the future research needs to further explore the internal interaction of micro system, the influence of time system and technological development on bystanders, and the complex interaction between social ecosystems, and design feasible intervention strategies to transform passive bystanders into active interveners.

Pancreatic cancer is a worldwide medical and health problem.Due to its high heterogeneity and malignant phenotype,the 5-year survival rate of pancreatic cancer is only 7.2%,which is a serious threat to human health.The biological mechanism and drug development research of pancreatic cancer often rely on the traditional two-dimensional culture models(cell lines)and patient-derived xenograft models.However,cell lines lack the three-dimensional environment and heterogeneity of the tumor,while xenograft models have the disadvantages of long culture time,low success rate and difficulty in carrying out high-throughput drug screening.There is an urgent need to develop three-dimensional culture models that can highly reflect the characteristics and molecular variation of pancreatic cancer.As a three-dimensional culture model developed in recent years,human-derived pancreatic cancer organoids are multicellular units extracted from tissue samples and embedded in extracellular matrix gels after mechanical and enzymatic digestion,which can reproduce the histological characteristics and organ characteristics of the original patient,and even have the functions of the original organ.With the continuous development and improvement of pancreatic cancer organoids culture system,its simple,economical and stable culture technology has been gradually established,which promotes the application of human pancreatic cancer organoids to high-throughput drug screening,individualized precision treatment and deeper pathogenesis and targeted drug development research.At the same time,human-derived pancreatic cancer organoids are also a novel semi-in vivo model for the study of clinical molecular typing of pancreatic cancer,especially for the study of etiology,molecular characteristics,histomorphology and somatic mutation burden of patients with high mutation rate and high heterogeneity.The construction of human pancreatic cancer organoid biobank with large sample size is a new platform for biology,basic medicine and clinical science oncology research,which provides a reliable resource for the in-depth study of the pathogenesis of pancreatic cancer and the development of treatment strategies.In summary,the research progress of human pancreatic cancer organoids promotes the application of laboratory models that recapitulate the characteristics of clinical patients,improves the connection between basic laboratory research and clinical patients,and provides clinical sources for drug screening,pathogenesis research,individualized treatment strategies and the construction of biobanks.Therefore,this article reviewed the latest research progress of human pancreatic cancer organoids,in order to provide reference for researchers engaged in the research of human pancreatic cancer organoids.

Objective:To explore the characteristics and typology of self-care behavior among patients with chronic heart failure (CHF), and analyze their influencing factors.Methods:A cross-sectional study was used. A total of 318 patients with CHF who were hospitalized in the Heart Center of Zhongshan Hospital, Fudan University from November 2022 to July 2023 were selected by continuous enrollment method. The General Information Questionnaire, Heart Failure Self-care Index Scale, Brief Illness Perception Questionnaire, Self-efficacy for Managing Chronic Disease 6-item Scale, Perceived Social Support Scale, Atlanta Heart Failure Knowledge Test-V2 and Self-Care Confidence Scale were used to investigate. Latent profile analysis was utilized to delineate the characteristics and subtypes of self-care behaviors in CHF patients and examine the influencing factors.Results:A total of 291 patients were included in this study, including 190 males and 101 females, aged 67 (61, 74) years old. The analysis identified three latent categories of self-care behaviors among CHF patients: 26 cases in high self-care group, 131 cases in moderate self-care with deficiencies in maintenance and symptom perception group, and 134 cases in low self-care group.Ordered multicategorical Logistic regression analysis revealed that age ( OR=1.023, 95% CI 1.001-1.046, P<0.05), self-care confidence ( OR=0.859, 95% CI 0.817-0.904, P<0.01), and social support ( OR=0.966, 95% CI 0.940-0.993, P<0.05) were the factors influencing the potential categories of self-care behavior in CHF patients. Conclusions:The study identifies distinct categorical characteristics of self-care behaviors in patients with CHF. Healthcare professionals can leverage these findings to identify the self-care behavior characteristics and influencing factors for each patient category at an early stage, thereby providing personalized and precise support strategies to help patients enhance self-care behaviors.

Objective To analyze the postoperative therapeutic effect of prokinetic agents in patients after tricuspid valve replacement （TVR） under cardiopulmonary bypass. Methods Patients received TVR under cardiopulmonary bypass （during June 2010 to December 2021） in the department of Cardiovascular Surgery of the First Affiliated Hospital of Naval Medical University were selected as the subjects of our study. The data of basic characteristics, first postoperative defecation time and postoperative recovery condition were collected and retrospectively analyzed in the patients taking prokinetic agents within three days after surgery （prevention group） and patients not taking prokinetic agents within three days after surgery （control group）. Results A total of 184 patients were selected, including 101 in the prevention group and 83 in the control group. The first defecation time of patients in the prevention group was significantly earlier than that in the control group （P<0.05）. The incidences of abdominal distension and pulmonary infection in the prevention group were significantly lower than that in the control group. The length of time in ICU, postoperative mechanical ventilation and nasogastric tube decompression in the prevention group were significantly shorter than that in the control group （P<0.05）. Conclusion Taking prokinetic agents within three days after TVR under cardiopulmonary bypass could effectively improve the prognosis of patients.

Objective To explore the establishment of a prognostic model based on machine learning algorithm to predict primary graft dysfunction(PGD)in patients with idiopathic pulmonary fibrosis(IPF)after lung transplantation.Methods Clinical data of 226 IPF patients who underwent lung transplantation were retrospectively analyzed.All patients were randomly divided into the training and test sets at a ratio of 7∶3.Using regularized logistic regression,random forest,support vector machine and artificial neural network,the prognostic model was established through variable screening,model establishment and model optimization.The performance of this prognostic model was assessed by the area under the receiver operating characteristic curve(AUC),positive predictive value,negative predictive value and accuracy.Results Sixteen key features were selected for model establishment.The AUC of the four prognostic models all exceeded 0.7.DeLong and McNemar tests found no significant difference in the performance among different models(both P＞0.05).Conclusions Based on four machine learning algorithms,the prognostic model for grade 3 PGD after lung transplantation is preliminarily established.The overall prediction performance of each model is similar,which may predict the risk of grade 3 PGD in IPF patients after lung transplantation.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.