Objective: To analyze the developmental trajectories of clustered health risk behaviors and their association with self-esteem and lonelinesss among junior high school students, so as to provide a reference for formulating comprehensive prevention and control measures of health risk behaviors among adolescents. Methods: In October 2023, 1 165 first year junior high school students from two schools of Jishou City in Hunan Province were selected by convenient sampling method for three follow up surveys (T1:October 2023; T2:April 2024; T3:October 2024). The Adolescent Health Risk Behavior Questionnaire, Rosenberg Self esteem Scale and Loneliness Scale were used to assess health risk behaviors, self esteem and loneliness, respectively. Latent growth curve modeling and latent growth mixture modeling were applied to analyze the developmental trajectories of clustered health risk behaviors among junior high school students. Logistic regression was used to analyze the association of the developmental trajectories of clustered health risk behaviors with self esteem and loneliness among junior high school students. Results: The overall developmental trajectories among junior high school students showed a declining trend (intercept=0.15, slope=-1.65, both P <0.05), with three heterogeneous categories:low risk improvement group ( n =862, 74.0%), moderate risk stable group ( n =260, 22.3%), and high risk deterioration group ( n =43, 3.7%). After adjusting the status of the left behind individuals，using the low risk improvement group as the reference category in multinomial Logistic regression analysis, results indicated that higher loneliness scores among junior high school students increased the risks of belonging to the moderate risk stable group ( OR=1.02, 95%CI =1.00- 1.04 ) and the high risk deterioration group ( OR=1.04, 95%CI =1.00-1.08), while higher self esteem scores reduced the risks of belonging to the moderate risk stable group ( OR=0.93, 95%CI =0.91-0.96) and the high risk deterioration group ( OR=0.88, 95%CI =0.83-0.94) (all P <0.05). Conclusions The overall trend of clustered health risk behaviors among junior high school students gradually improves, and the self esteem and loneliness are significant correlative factors. Targeted intervention measures should be developed for the junior high school students, with a focus on enhancing their self esteem and alleviating loneliness.

BackgroundSuicide among adolescents has become a serious public health issue， with suicidal ideation serving as a necessary precursor to suicide attempts and death. Previous research suggests that campus exclusion， depression， and psychological resilience are closely associated with the development of suicidal ideation in individuals. However， there is a lack of longitudinal research to deeply explore the relationship between each influencing factor and suicidal ideation. ObjectiveTo explore the impact of campus exclusion on suicidal ideation among adolescents， as well as the mediating role of depression and the moderating role of resilience， so as to provide references for formulating strategies for preventing and intervening in adolescent suicide. MethodsAUsing a longitudinal research design， in November 2023， 1 226 students from 21 classes （4 classes per grade in junior high school and 3 classes per grade in senior high school） from a junior high school and a senior high school in a certain area of Shandong Province were selected as the research subjects. The Ostracism Experience Scale for Adolescents （OES-A）， the Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， and the Resilience Scale for Chinese Adolescents （RSCA） were used for assessment. The PHQ-9 suicide ideation item was evaluated again three months after the baseline survey （the two suicide ideation evaluations were respectively denoted as T1 and T2 respectively. Spearman correlation analysis was used to examine the relationships among scale scores. Model 4 and model 59 in the SPSS macro program Process 4.2 were used to test the mediating effect of depression between school exclusion and suicide ideation， as well as the moderating effect of psychological resilience on the three paths. ResultsCorrelation analysis showed that OES-A score was positively correlated with PHQ-9 score and suicidal ideation item score （T2）， and PHQ-9 score was also positively correlated with suicidal ideation item score （T2） （r=0.361， 0.292， 0.508， P<0.01）. RSCA score was negatively correlated with OES-A， PHQ-9， and suicidal ideation （T2） scores （r=-0.500， -0.676， -0.459， P<0.01）. Campus exclusion positively predicted suicidal ideation （T2） and depression （β=0.081， 0.281， P<0.01）， while depression positively predicted suicidal ideation （T2） （β=0.108， P<0.01）. The mediation analysis revealed an effect size of 0.030 （95% CI： 0.019~0.043， P<0.01）， accounting for 37.35% of the total effect. Psychological resilience moderated the relationships between campus exclusion and depression， campus exclusion and suicidal ideation （T2）， and depression and suicidal ideation （T2） （β=-0.059， -0.049， -0.062， P<0.01）. ConclusionA moderated mediation model exists among campus exclusion， depression， resilience， and adolescent's suicidal ideation. Psychological resilience moderates the associations between campus exclusion， depression and suicidal ideation across all three paths. ［Funded by Beijing Municipal Health Commission Clinical Research Excellence Program， （number， BRWEP2024W072130101）；Beijing Municipal Hospital Management Center Summit Program， （number， DFL20221701）］

OBJECTIVE: To investigate the effect of human adipose-derived mesenchymal stem cells (hASCs) exosomes on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) extracted from osteoporotic mice, and to evaluate the effect of hASCs exosomes on preventing bone loss induced by estrogen deficiency. METHODS: hASCs exosomes were extracted by ultracentrifugation. The osteoporotic mice were established by bilateral ovariectomy (OVX). BMSCs were isolated from osteo-porotic mice and cultured for further analysis. In the experimental group, these BMSCs were exposed to an osteogenic induction medium supplemented with hASCs exosomes to evaluate their potential effects on osteogenesis. In contrast, the control group was treated with the same osteogenic induction medium, but without the addition of hASCs exosomes, to serve as a baseline comparison for the study. To comprehensively assess the osteogenic differentiation of BMSCs influenced by hASCs exosomes, alkaline phosphatase (ALP) staining, ALP activity quantitative analysis and quantitative reverse transcription polymerase chain reaction (qPCR) were performed. These evaluations provided critical insights into the role of hASCs exosomes in promoting osteoblast differentiation and bone formation in osteoporotic conditions. The fluorescence labeled hASCs exosomes were injected via the tail vein to observe the biodistribution of exosomes. Two weeks after OVX, the mice were divided into three groups: The experimental group consisted of estrogen-deficient mice receiving hASCs exosome injections; the negative control group consisted of estrogen-deficient mice receiving phosphate-buffered saline (PBS) injections; and the positive control group consisted of mice that underwent Sham surgery and received PBS injections.The injections were administered once every 3 days, for a total of 8 injections. Afterward, the femurs were collected from the mice, and micro-computed tomography (micro-CT) was performed to measure bone mineral density and conduct bone morphometric analysis. RESULTS: hASCs exosomes were successfully extracted using ultracentrifugation. After the induction by hASCs exosomes, ALP staining and ALP activity in the BMSCs extracted from osteoporotic mice were significantly enhanced, the expression of osteogenesis related genes in BMSCs were significantly up-regulated. More trabecular bone and higher bone mineral density were observed in estrogen-deficient mice injected with hASCs exosomes compared with estrogen-deficient mice injected with PBS, and there was no significant decrease in bone mineral density compared with the Sham operation group. CONCLUSION hASCs exosomes promoted the osteogenic differentiation of BMSCs extracted from osteoporotic mice. hASCs exosomes prevented bone loss induced by estrogen deficiency.
Animals ; Mesenchymal Stem Cells/cytology* ; Exosomes ; Estrogens/deficiency* ; Humans ; Osteogenesis ; Cell Differentiation ; Female ; Mice ; Osteoporosis/prevention & control* ; Ovariectomy ; Adipose Tissue/cytology* ; Cells, Cultured

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

OBJECTIVES: To examine the changes in serum levels of endoplasmic reticulum stress (ERS) proteins GRP78/CHOP in patients with lupus nephritis (LN) and analyze their diagnostic value and association with renal pathological features. METHODS: From a sample bank established based on a multicenter cohort study of systemic lupus erythematosus (SLE), 60 LN patients and 35 SLE patients without renal involvement were randomly selected. ELISA was used to detect serum levels of GRP78 and CHOP in the patients to analyze their correlation with clinical features and their diagnostic ability for LN and active LN. MRL/lpr mice were used as an animal model of LN to examine their serum levels of GRP78 and CHOP expression and renal expressions of endoplasmic reticulum apoptosis-related proteins. RESULTS: Serum GRP78 and CHOP levels were significantly higher in LN patients than in SLE patients without renal involvement (P<0.05), and were also higher in active LN patients than in patients in the stable phase (P<0.05). Correlation analysis indicated that serum GRP78 and CHOP levels were positively correlated with SLEDAI scores and 24-h urinary protein. ROC analysis showed that CHOP had a high diagnostic ability for LN (AUC=0.762) and active LN (AUC=0.933). Consistent with the clinical findings, serum GRP78 and CHOP levels were elevated in LN mice, and the expressions of PERK and IRE1α pathway proteins were also increased in the kidneys of the mice. TUNEL staining showed increased renal cell apoptosis and elevated renal expressions of apoptosis-related proteins in LN mice. CONCLUSIONS Serum levels of GRP78/CHOP are increased in LN patients possibly in association with ERS-induced apoptosis mediated by the PERK/IRE1α dual pathway.
Endoplasmic Reticulum Chaperone BiP ; Lupus Nephritis/blood* ; Transcription Factor CHOP/blood* ; Heat-Shock Proteins/blood* ; Animals ; Apoptosis ; Humans ; Mice ; Mice, Inbred MRL lpr ; Female ; Adult ; Endoribonucleases/metabolism* ; Male ; eIF-2 Kinase/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Young Adult ; Endoplasmic Reticulum Stress ; Kidney/metabolism* ; Middle Aged ; Signal Transduction

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Osteoradionecrosis of the jaws (ORNJ) is among the most severe oral complications following radiotherapy for head and neck tumors. It is essentially a form of pathological necrosis of the jawbone induced by radiation therapy. ORNJ is defined as bone damage, primarily characterized by inflammation and necrosis, occurring in the jawbone within the irradiated area and accompanied by soft tissue injury, persisting for more than 3 months without spontaneous healing. Diagnosis requires exclusion of other potential etiologies, including primary tumor recurrence, medication-related osteonecrosis, and radiation-induced neoplasms of the jawbone, etc. In this review, recent advances in the epidemiology, risk factors, diagnosis, classification and staging, dosimetric parameters, pathogenesis, treatment, and prevention of radiation-induced osteonecrosis of the jaws were summarized.

Objective:To investigate the effects of different doses of whole abdominal ultra‐high dose rate (FLASH) irradiation on the intestinal microbiota of mice.Methods:A total of 25 healthy male C57BL/6J mice were randomly divided into the control ( n=5) and FLASH irradiation groups ( n=20) by simple randomization method, and the FLASH irradiation group was further divided into different radiation dose subgroups of 10, 15, 20, 25 Gy, 5 in each group. The mice were irradiated with a single whole abdomen at a dose rate of 100 Gy/s, then sacrificed 3.5 d after irradiation. Fresh fecal specimens and intestinal tissues of mice were collected for 16S rRNA sequencing, microbiota analysis, hematoxylin eosin (HE) staining and injury severity score analysis. Two-group comparison was performed by independent sample t-test. Multi-group comparison was conducted by one-way ANOVA. Results:HE staining revealed that the whole abdomen FLASH irradiation caused varying degree of intestinal injury in mice, and the intestinal injury reaction was aggravated with the increase of irradiation dose. β‐diversity analyses showed that there were differences in the composition of intestinal microbiota between FLASH irradiation group and control group ( P=0.001), but the differences in the relative abundance of the species between the irradiation groups at different doses were relatively small, and there were their own dominant genera of bacteria. Comparison of different doses of FLASH irradiation groups with control group screened out 16 species of bacteria with shared differences at the genus level, in which Lactobacillus, Ligilactobacillus and unclassified Lactobacillus were more abundant in the control group, while Escherichia, Allobaculum, and Muribaculum were more abundant in the FLASH irradiation groups. Conclusions:The whole‐abdominal FLASH irradiation induces intestinal damage in mice, and the intestinal damage response is worsened with the increase of irradiation dose. Different doses of whole abdominal FLASH irradiation alter the intestinal microbiota composition of mice. Sixteen species of common intestinal differential microbiota at the genus level are screened out in the different doses of FLASH irradiation groups compared with the control group, which may serve as a marker for measuring intestinal injury in mice irradiated with whole‐abdominal FLASH.

Objective:To analyze the trend of ovarian cancer incidence in Qidong City from 1972 to 2021 and evaluate the age, period, and cohort effect.Methods:The ovarian cancer incidence data from 1972 to 2021 were extracted from the Qidong Cancer Registry Database, the crude incidence rate (CR), age standardized rate by Chinese population (ASR-C), age standardized rate by world population (ASR-W), and average annual percent change (AAPC) were calculated. The age-period-cohort model was used to analyze the age, period, and birth cohort effects of the ovarian cancer incidence in Qidong from 1972 to 2021.Results:From 1972 to 2021, a total of 1 007 cases of ovarian cancer occurred in Qidong. The AAPC values of CR, ASR-C, and ASR-W were 7.02% , 5.17%, and 5.12% , respectively (all P＜0.001). The time trends showed that, the AAPC values of the age groups of 0-34, 35-44, 45-54, 55-64, 65-74, and over 75 years old were 4.10%, 4.74%, 6.02%, 4.86%, 4.23%, and 5.18%, respectively (all P＜0.05). The age effect showed that the incidence rate of ovarian cancer increased obviously from the 45-49 year-old group, reaching a peak of 20.67/100 000 in the 75-79 year-old group. Compared with the 1992-1996 group, the period of 2002-2021 had significant effects on the incidence rise of ovarian cancer (all P＜0.05), and the incidence rate ratio ( RR) increased with the period: in 2017-2021 the RR was 3.86 (95% CI: 2.72-5.47). Using births from 1952 to 1956 as the reference group, the RR increased slowly from 0.12 (95% CI: 0.02-0.91) in 1892-1896, and peaked in 2007-2011 with an RR of 18.05 (95% CI: 3.51-92.87). The birth cohorts in 1967-2011 had significant effects on the incidence rise of ovarian cancer (all P＜0.05). The Waldχ 2 test of the age-period-cohort model showed that there were significant differences in the age, period, and birth cohort effects (all P＜0.001). Conclusions:The incidence of ovarian cancer in Qidong was on the rise. Age, period, and cohort were the main factors affecting the incidence of ovarian cancer. The middle-aged and elderly women were the focus of ovarian cancer prevention and control.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.