Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms. Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient. Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424−3.345, p ＜ 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p ＜ 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p ＜ 0.05), and its expression was even higher in T allele carriers (p ＜ 0.05). miR-182 could directly target and suppress BDNF, leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression. Conclusion The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Objective: To explore the effect of interferon regulatory factor 2 binding protein 2 ( IRF2BP2) on the proliferation of acute myeloid leukemia ( AML) cells and its molecular mechanism． Methods: The CRISPR-Cas9 gene editing technology was used to knock out IRF2BP2 in human AML cell lines Kasumi-1 and U937，and West- ern blot was performed to detect the knockout efficiency of IRF2BP2 protein．Cell morphology was observed using a microscope．Cell phenotypes were analyzed by CCK-8 assay，colony formation experiments，and flow cytometry． RNA-Seq was performed to identify differentially expressed genes between the IRF2BP2 knockout group and the control group in the U937 cell line．Gene Set Enrichment Analysis ( GSEA) was conducted to explore the down- stream molecular mechanisms．Western blot was used to detect the expression of downstream differentially expressed genes．The Cleavage Under Targets and Tagmentation ( CUT＆Tag) technique was applied to identify the direct tar- gets of the IRF2BP2 protein，and the corresponding binding signals were visualized using the Integrated Genomics Viewer ( IGV) ． Results: Compared with the control group，after knocking out IRF2BP2，the CCK-8 experiment showed that AML cell proliferation was inhibited ( P ＜0. 05) ; the number of colonies in the IRF2BP2 knockout group decreased ( P＜0. 05) ，and the proportion of G1 phase was prolonged ( P＜0. 05) ; in U937 cell lines，knoc- king out IRF2BP2 resulted in significant enrichment of differential genes in myelocytomatosis oncogene ( MYC) -re- lated signaling pathways，and the protein expression levels of pathway molecules MYC，cyclin-dependent kinase 4 ( CDK4) ，and cyclin － dependent kinase 2 ( CDK2 ) decreased with the downregulation of IRF2BP2; using IRF2BP2 antibodies in U937 cell lines for CUT＆Tag experiments，IGV visualization analysis showed a significant increase in signal peaks in the MYC promoter region． Conclusion IRF2BP2 protein affects the cell cycle and pro- liferation of AML cells by targeting and regulating MYC．

Objective:To compare the dosimetric differences between volumetric modulated arc therapy(VMAT)and helical tomotherapy(HT)in undergoing protective plan for pelvic bones of patients with cervical cancer.Methods:A total of 40 patients with cervical cancer,who underwent radiotherapy at the First Affiliated Hospital of Bengbu Medical University from January 2023 to February 2024,were selected for this study.The target volumes and organs at risk(OARs)were delineated after the information of computed tomography(CT)simulation images were acquired from each patient.The pelvic bone was alone delineated as OAR.Two kinds of bone marrow dose-limiting radiotherapy plans,coplanar dual-arc VMAT and HT,were respectively designed for each patient by using the treatment planning system(TPS)of radiotherapy.A statistical analysis was conducted to compare the dose parameters of target volume,conformity,homogeneity,OAR dose-volume,mean dose,and maximum dose of point between the two kinds of plans.Results:Both the VMAT and HT plans could meet the requirements of target volume and OARs for dose.For general OARs,the dose-volume percentage(V40 Gy)of V40 Gy at bladder,mean dose(Dmean),rectal V40 Gy,maximum dose(Dmax)at small intestine point of HT plan were respectively(38.97±2.29)%,(38.06±0.45)Gy,(61.50±2.51)%and(50.82±0.36)Gy.The differences of them between HT plan and VMAT plan were statistically significant(t=25.46,13.99,1.56,10.93,P<0.05).The V10 Gy,V20 Gy,V30 Gy and Dmean of VMAT plan were respectively(70.76±2.51)%,(60.84±3.29)%,(52.40±2.56)%and(32.02±4.33)Gy for pelvic bones,which were significantly lower than those of HT plan,and the differences of them between two kinds of plans were also statistically significant(t=-20.68,-13.23,-7.73,-10.26,P<0.05).Conclusion:The HT plan can provide the optimal dose distribution for target region in radiotherapy for patients with cervical cancer,which can better protect OAR nearby target region.VMAT plan has a significant advantage in low-dose regions of protecting pelvis.Thus,individualized treatment design should be conducted according to the conditions of each patient in clinical treatment.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Objective To develop a graded early mobility implementation pathway for critically ill adult patients in tertiary hospitals in Beijing and to preliminarily validate its feasibility and effectiveness.Methods Based on the"goal-directed"early mobility concept,a graded early mobility implementation pathway for critically ill patients was developed through evidence synthesis and the Delphi method,consisting of 3 components:patient inclusion,mobility implementation,and mobility evaluation.Using convenience sampling,patients meeting inclusion criteria in the general ICU of a tertiary hospital in Beijing from October 2024 to January 2025 were selected as participants.Among them,25 patients admitted from December 2024 to January 2025 were assigned to an experimental group and received early mobility interventions following the developed pathway.25 patients admitted from October to November 2024 served as a control group and received routine ICU mobility care.Outcomes including diaphragm excursion,muscle strength,ICU length of stay,and adverse events were compared between the 2 groups.Results The graded early mobility pathway achieved an implementation rate of 70.05％in the experimental group,significantly higher than it in the control group(P＜0.001),without increasing adverse events.Post-intervention diaphragm excursion in the experimental group was significantly greater than that in the control group(P=0.018).Conclusion The developed graded early mobility implementation pathway for ICU patients demonstrates scientific rigor and clinical practicality.It provides a reference for the widespread and effective implementation of early mobility in ICUs,standardizing its clinical application.