BackgroundNon-suicidal self-injury （NSSI） behavior among adolescents has become a global public health concern. Anxiety and depression are considered key factors influencing NSSI behavior， while social support may play a protective role in alleviating emotional and behavioral issues. However， existing research has primarily focused on the direct impact of individual factors on NSSI behavior， with insufficient exploration of the combined effects of anxiety， depression and social support. ObjectiveTo investigate the direct effect of anxiety on NSSI， the mediating role of depression and the moderating role of social support in relationship between anxiety and NSSI behavior， thus to provide references for the prevention and intervention of NSSI behavior among adolescents. MethodsIn February 2022， a total of 40 820 students in grades 7 to 12 across 10 middle schools in a district of Chengdu were selected as participants， and they were assessed using Generalized Anxiety Disorder Scale-7 item （GAD-7）， Patient's Health Questionnaire Depression Scale-9 item （PHQ-9）， Social Support Scale for Urban Students （SSSUS） and Adolescent Self-Harm Scale （ASHS）. Pearson correlation analysis was conducted to examine the correlations between scale scores among adolescents with NSSI behaviors. Mediation and moderation analyses were performed using Process 3.5 in SPSS， and the significance was tested with bootstrapping. The interaction was visualized by using simple slope analysis. ResultsAmong 34 534 （84.60%） valid respondents， 542 adolescents （1.57%） reported engaging in NSSI behavior. Significant differences in gender， GAD-7 scores， PHQ-9 scores， and SSSUS scores were observed between NSSI behavior group and non-NSSI group （χ²/t=62.889， 71.120， 94.365， -41.464， P<0.01）.Adolesents with NSSI showed positive correlations between GAD-7 scores and both ASHS and PHQ-9 scores （r=0.158， 0.166， P<0.01）. PHQ-9 scores were positively correlated with ASHS scores （r=0.364， P<0.01）， but negatively correlated with SSSUS scores （r=-0.290， P<0.01）. SSSUS scores were negatively correlated with ASHS scores （r=-0.247， P<0.01）. Depression partially mediated the relationship between anxiety and NSSI behavior， with an effect size of 0.544 （95% CI： 0.162~0.944）， accounting for 35.79% of the total effect. Social support moderated the relationship between depression and NSSI bahavior， with an effect value of -0.082 （95% CI： -0.135~-0.029）. ConclusionAnxiety not only directly influences NSSI bahavior among adolescents， also indirectly exacerbates it through depression， while social support mitigates the impact of depression on NSSI behavior. ［Funded by Youth Project of National Natural Science Foundation of China （number， 82401812）； Project of Health Commission of Sichuan Province （number， 24LCYJPT18）］

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective To establish an ultra-high performance liquid chromatography(UPLC)fingerprint and multi-index content determination method of Siraitiae fructus standard decoction.Methods 15 batches of Siraitiae fructus from different producing areas were collected,Siraitiae fructus standard decoction was prepared according to Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules,and the extract rate was calculated.UPLC was used to establish the fingerprint of 15 batches of Siraitiae fructus standard decoction and determine the contents of 11-O-mogroside V,kaempferitrin and mogroside V,which were the main effective components.The chemometrics analysis was used to evaluate the quality of Siraitiae fructus standard decoction and find possible quality markers.Results The extraction rate of 15 batches Siraitiae fructus standard decoction ranged from 24.79％to 34.95％.There were 16 common peaks in the fingerprint,and 4 components were identified.The Siraitiae fructus standard decoction was divided into 2 categories by chemometrics analysis,among which samples from Liuzhou,Guangxi were in one category and samples from Guilin,Guangxi were in another category.Seven differential markers were screened out under the condition of variable importance projection value,and the order was as follows:peak 8＞peak 7＞peak 5＞peak 12(kaempferitrin)＞peak 1＞peak 13＞peak 4.The contents of kaempferitrin,11-O-mogroside V and mogroside V in samples from Guilin,Guangxi were slightly higher than those in samples from Liuzhou,Guangxi.Conclusion The UPLC fingerprint and content determination method established in this study are feasible,which can provide a basis for the quality evaluation of Siraitiae fructus.The results of principal component analysis show that kaempferol is likely to become a quality marker of Siraitiae fructus.

Objective To explore the correlation between serum fibroblast growth factor-23 (FGF23) concentration and heart failure and all-cause death in patients with end-stage renal disease (ESRD).Methods The prospective cohort study design was used in the present study.The ESRD patients who were admitted to the department of ne-phropathy in the Hospital and without heart failure symptoms were recruited in this study.The data of patients was collected through baseline questionnaires, physical examinations, echocardiography, and laboratory examinations.The serum FGF23 levels were measured by enzyme-linked immunosorbent assay (ELISA) .The follow-up time was 2 years.The onset of heart failure (ACC/AHA stage C-D) and all-cause death were composite endpoint events.The Cox proportional risk model was used to explore the risk factors of outcome events.Through subgroup analyses and interaction analyses, further exploration was conducted to determine whether there was heterogeneity in the as-sociation between FGF23 and outcome events in different subgroups.Results Ultimately,107 ESRD patients were included in this study, with an average age of (52.00 ± 12.51) years.There were 39 males (36.45％), and the median follow-up time was 23 months (21, 25 months).There were 32 (29.9％) outcome events, of which 22 (20.6％) onset of heart failure and 10 (9.3％) all-cause of deaths.The results of this study showed that the con-centration of FGF23 in the outcome event group was significantly higher than that in the non-event group [ (4.40 ± 1.16) pmol/ml vs (3.85 ± 0.82) pmol/ml,P<0.05].The Cox proportional risk model showed that the elevated FGF23 was associated with increased risk of the composite endpoint events in ESRD patients (HR=1.730 , 95％CI:1.164-2.570 , P=0.007) .Subgroup analyses showed that there was an interactive effect between FGF23 levels and gender on the risk of cardiovascular outcome events.Especially in male ESRD patients, the increased FGF23 level was correlated with a higher risk of cardiovascular events (P-interaction <0.05).Conclusion Elevated serum FGF23 is an independent risk factor for the onset of heart failure and all-cause of mortality in ESRD patients, especially in male patients.

Objective Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)generally have small sample sizes and a class imbalance.However,most machine learning models are designed based on balanced data and lack interpretability.This study aimed to propose a traditional Chinese medicine(TCM)diagnostic model for HBV-ACLF based on the TCM syndrome differentiation and treatment theory,which is clini-cally interpretable and highly accurate. Methods We collected medical records from 261 patients diagnosed with HBV-ACLF,includ-ing three syndromes:Yang jaundice(214 cases),Yang-Yin jaundice(41 cases),and Yin jaun-dice(6 cases).To avoid overfitting of the machine learning model,we excluded the cases of Yin jaundice.After data standardization and cleaning,we obtained 255 relevant medical records of Yang jaundice and Yang-Yin jaundice.To address the class imbalance issue,we employed the oversampling method and five machine learning methods,including logistic regression(LR),support vector machine(SVM),decision tree(DT),random forest(RF),and extreme gradient boosting(XGBoost)to construct the syndrome diagnosis models.This study used precision,F1 score,the area under the receiver operating characteristic(ROC)curve(AUC),and accuracy as model evaluation metrics.The model with the best classification per-formance was selected to extract the diagnostic rule,and its clinical significance was thor-oughly analyzed.Furthermore,we proposed a novel multiple-round stable rule extraction(MRSRE)method to obtain a stable rule set of features that can exhibit the model's clinical in-terpretability. Results The precision of the five machine learning models built using oversampled balanced data exceeded 0.90.Among these models,the accuracy of RF classification of syndrome types was 0.92,and the mean F1 scores of the two categories of Yang jaundice and Yang-Yin jaun-dice were 0.93 and 0.94,respectively.Additionally,the AUC was 0.98.The extraction rules of the RF syndrome differentiation model based on the MRSRE method revealed that the com-mon features of Yang jaundice and Yang-Yin jaundice were wiry pulse,yellowing of the urine,skin,and eyes,normal tongue body,healthy sublingual vessel,nausea,oil loathing,and poor appetite.The main features of Yang jaundice were a red tongue body and thickened sublin-gual vessels,whereas those of Yang-Yin jaundice were a dark tongue body,pale white tongue body,white tongue coating,lack of strength,slippery pulse,light red tongue body,slimy tongue coating,and abdominal distension.This is aligned with the classifications made by TCM experts based on TCM syndrome differentiation and treatment theory. Conclusion Our model can be utilized for differentiating HBV-ACLF syndromes,which has the potential to be applied to generate other clinically interpretable models with high accura-cy on clinical data characterized by small sample sizes and a class imbalance.

This paper aims to review treatment delay in first-episode schizophrenia,depression,and bipolar disorder,and to compare related factors of treatment delay in the three first-episode mental disorders.It is found that increased patient responsibility,stigma,lack of disease-related knowledge,lack of access to resources,and insuffi-cient medical support lead to delay treatment,and making patients to have longer course,heavier symptoms,and lower social functions.

Objective:To explore the efficacy and safety of endoscopic radial incision (ERI) for congenital membranous duodenal stenosis (MDS).Methods:The clinical data of 13 children with MDS receiving ERI in the Department of Gastroenterology of Xi'an Children's Hospital from May 2017 to December 2021 were reviewed and analyzed. The perioperative management, surgical procedures, postoperative complications and follow-up were summarized.Results:There were 5 boys and 8 girls with a median disease duration of 8 (2-20) months, and the median age of diagnosis was 13 months (5-30 months). The septum of 10 cases (10/13) was located in the descending part of the duodenum, and that of 3 cases (3/13) in the horizontal part. The papilla of 1 case (1/13) opened on the septum, that of 3 cases (3/13) within 5 cm of the mouth side of the septum, and that of 9 cases (9/13) within 5 cm of the anal side of the septum. The median diameter of the septal aperture was 3 mm (2-6 mm). All 13 children successfully underwent ERI with a median operation time of 20 min (15-32 min). The average surgical incision was 3 strokes (2-4 strokes), and the endoscope with outer diameter 9.9 mm could pass stenosis after ERI. The median incision diameter was 10 mm (10-12 mm). All patients achieved relief of clinical symptoms after ERI. One patient (1/13) suffered from the postoperative delayed bleeding, which was stopped by endoscopic titanium clamping. No intestinal perforation or duodenal papilla injury occurred, and median postoperative hospital stay was 6 days (5-10 days). The upper gastrointestinal angiogram and gastroscopy were repeated 3 months after ERI, and the median diameter of stenosis was 12 mm (10-15 mm), which was significantly dilated compared with before. The mean body weight increase at 1 month after ERI was 1.20 kg (0.50-1.80 kg), and the mean body weight increase at 3 months was 3.50 kg (2.50-4.00 kg), which reached the normal body weight of the same age.Conclusion:ERI is safe and effective for the treatment of MDS in children, and shows good clinical application and promotion value.

Objective:To compare the difference between virtual surgical planning(VSP)position and postoperative real position of maxilla and condyle,and to explore the degree of intraoperative realization of VSP after orthognathic surgery.Methods:In this study,36 patients with mandibular protrusion de-formity from January 2022 to December 2022 were included.All the patients had been done bilateral sagittal split ramus osteotomy(SSRO)combined with Le Fort Ⅰ osteotomy under guidance of VSP.The VSP data(T0)and 1-week postoperative CT(T1)were collected,the 3D model of postoperative CT was established and segmented into upper and lower jaws in CCMF Plan software.At the same time,accor-ding to the morphology of palatal folds,the virtual design was registered with the postoperative model,and the unclear maxillary dentition in the postoperative model was replaced.Then the postoperative model was matched with VSP model by registration of upper skull anatomy that was not affected by the opera-tion.The three-dimensional reference plane and coordinate system were established.Selecting anatomical landmarks and their connections of condyle and maxilla for the measurement,we compared the coordinate changes of marker points in three directions,and the angle changes between the line connecting the marker points and the reference plane to analyze the positional deviation and the angle deviation of the postoperative condyle and maxilla compared to VSP.Results:The postoperative real position of the maxilla deviates from the VSP by nearly 1 mm in the horizontal and vertical directions,and the anteropos-terior deviation was about 1.5 mm.In addition,most patients had a certain degree of counterclockwise rotation of the maxilla after surgery.Most of the bilateral condyle moved forward,outward and downward(the average distance deviation was 0.15 mm,1.54 mm,2.19 mm,respectively),and rotated forward,outward and upward(the average degree deviation was 4.32°,1.02°,0.86°,respectively)compared with the VSP.Conclusion:VSP can be mostly achieved by assistance of 3D printed occlusal plates,but there are certain deviations in the postoperative real position of maxilla and condyle compared with VSP,which may be related to the rotation axis of the mandible in the VSP.It is necessary to use patient personalized condylar rotation axis for VSP,and apply condylar positioning device to further improve surgical accuracy.

Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.