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 clinical value of inflammatory prognostic index combined with dual-source CT perfusion imaging in predicting early response of hepatocellular carcinoma(HCC)after transcatheter hepatic artery chemoembolization(TACE).Methods A total of 25 patients with HCC,who met the inclusion criteria and received initial TACE at the First Affiliated Hospital of Dali University of China from November 2022 to November 2023,were prospectively collected.CT perfusion scan was performed before TACE as well as in 30-40 days after TACE,and blood routine and blood biochemical data were collected.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to evaluate postoperative enhanced CT manifestations.Patients obtaining complete remission(CR)or partial remission(PR)were classified as effective group(n=14),and patients obtaining stable disease(SD)or progression disease(PD)were classified as ineffective group(n=11).The differences in CT perfusion imaging parameters and inflammatory parameters between the two groups were analyzed,and the predictive values of preoperative CT perfusion imaging parameters and inflammatory parameters for postoperative early response of HCC were evaluated.The cutoff value was taken at the maximum Youden index.Univariate analysis and multivariate analysis were used to analyze the effect of CT perfusion imaging parameters,inflammatory parameters and clinical features on the prognosis.The nomogram prediction model was constructed by using R software.Results The post-TACE arterial liver perfusion(ALP),hepatic perfusion index(HPI),blood flow(BF)and blood volume(BV)were significantly lower than their pre-TACE values(all P＜0.05).Afer TACE portal vein perfusion(PVP)was obviously higher than that before operation(P＜0.05).No statistically significant differences in the mean transit time(MTT),flow extraction product(FED),C-reactive protein(CRP),albumin(ALB),neutrophil/lymphocyte ratio(NLR)and inflammatory prognosis index(IPI)existed between the pre-TACE values and post-TACE values(all P＞0.05).The pre-TACE ALP,BF and FED in the effective group were significantly higher than those in the ineffective group,while the pre-TACE CRP and IPI in the effective group were remarkably lower than those in the ineffective group(P＜0.05).There were no statistically significant differences in pre-TACE PVP,HPI,MTT,BV,ALB and NLR between the effective group and the ineffective group before(all P＞0.05).In the effective group,the pre-TACE ALP,HPI,BF,BV and FED were obviously higher than their post-TACE values(all P＜0.05)preoperative PVP was significantly lower than postoperation(P＜0.05),while no statistically significant differences in MTT,CRP,ALB,NLR and IPI existed between the pre-TACE values and the post-TACE values(all P＞0.05).In the ineffective group,the pre-TACE HPI was prominently higher than the post-TACE value(P＜0.05),while no statistically significant differences in ALP,PVP,BF,BV,MTT,FED,ALB,CRP,NLR and IPI existed between the pre-TACE values and the post-TACE values(all P＞0.05).The pre-TACE ALP,BF,BV,FED,CRP and IPI had high predictive values in judging early response of HCC after TACE(all P＜0.05),the AUC values were 0.831,0.779,0.740,0.753,0.779 and 0.805 respectively,and the optimal cutoffs were 33.280 mL/100 mL min,61.860 mL/100 mL min,5.885 mL/100 mL,29.725 mL/100 mL min,30.465 mg/L,1.885 respectively.ALP combined with CRP had the highest predictive value for post-TACE early response of HCC,with an AUC of 0.968(95％CI:0.906-1.000,P＜0.05),ALP combined with IPI could significantly improve the predictive value,with an AUC of 0.961(95％CI:0.894-1.000,P＜0.05),with the sensitivity and specificity being 0.929 and 0.909 respectively.Multivariate analysis showed that pre-TACE ALP and CRP were the independent influencing factors for post-TACE early response of HCC(P＜0.05).The nomogram prediction model constructed based on the pre-TACE ALP and CRP could effectively predict the post-TACE early response of HCC,and the AUC value was 0.968(95％CI:0.908-1.000).Conclusion ALP and CRP can be used to predict the post-TACE early response of HCC,and the combination use of ALP and CRP can significantly improve the predictive value.

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.

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.

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

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 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.