OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） combined with neoadjuvant chemotherapy in the treatment of early triple-negative breast cancer （TNBC）. METHODS Randomized controlled trials （RCTs） comparing ICIs combined with neoadjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy alone （control group） were retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， Wanfang Data， and VIP databases， as well as relevant studies published at oncology academic conferences. The search period was from database inception to June 30， 2025. After literature screening， data extraction， and quality assessment， a meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 6 RCTs involving 3 786 patients were finally included. The meta-analysis results showed that the experimental group had superior event-free survival [HR＝0.73， 95%CI （0.62， 0.85）， P＜0.000 1]， overall survival [HR＝0.69， 95%CI （0.57， 0.84）， P＝0.000 3]， and pathological complete response （pCR） [OR＝1.57， 95%CI （1.37， 1.80）， P＜0.000 01] compared to the control group. The incidence of ≥grade 3 adverse event （AE）， severe AE （SAE）， and ≥ grade 3 immune-related adverse event （irAE） in the experimental group was significantly higher than that in the control group. There was no statistically significant difference between the two groups in the incidence of any AE or any irAE （P＞0.05）. Subgroup analysis revealed that， regardless of programmed cell death ligand 1 expression status （negative or positive），the pCR in the experimental group was significantly higher than that in the control group （P＜0.05）. Additionally， the pCR of the patients with positive lymph nodes in the experimental group was significantly higher to that in the ontrol group （P＜0.05）. There was no statistically significant difference in pCR between the two groups with negative lymph nodes （P＝0.09）. CONCLUSIONS ICIs combined with neoadjuvant chemotherapy can significantly improve event-free survival and overall survival in patients with TNBC， providing patients with long-term survival benefits. However， the risk of ≥ grade 3 AE， SAE and ≥ grade 3 irAE has increased.

Objective To investigate the expression characteristics of the transcription factor E2F2 in clear cell renal cell carcinoma (ccRCC), its impact on patient prognosis, and its potential role in the tumor immune microenvironment, with validation using clinical samples and functional assays. Methods RNA sequencing data and clinical information of ccRCC patients were obtained from the TCGA database; GSE53757 and GSE66272 datasets were downloaded from the GEO database as external validation cohorts. The expression difference of E2F2 between ccRCC tissue and normal tissue was compared, and the relationship between E2F2 expression and clinical pathological characteristics was analyzed. Kaplan-Meier (KM) survival analysis with log-rank test was performed to evaluate the effects of E2F2 on overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The prognostic efficacy of E2F2 in predicting 1-, 3- and 5-year survival was evaluated using receiver operating characteristic (ROC) curve. GSEA was performed to identify E2F2-related signaling pathways, and the ESTIMATE and CIBERSORT algorithms were used to assess the relationship between E2F2 expression level and tumor immune cell infiltration and immune microenvironment. Twenty pairs of surgically resected and pathologically confirmed ccRCC tissues and matched adjacent non-tumor tissues were collected from our hospital, and immunohistochemistry (IHC) was performed to detect the protein expression of E2F2. Human ccRCC cell line 786-O was used for functional assays;shRNA was used to knock down E2F2 expression (constructing stable shE2F2#1 and shE2F2#2 cell lines), and qRT-PCR and Western blot were performed to verify knockdown efficiency, followed by MTT, colony formation, and Transwell migration assays to evaluate the effects of E2F2 on the biological behaviors of ccRCC cells. Results E2F2 was significantly upregulated in ccRCC tissues (the same results in the verification set). Higher E2F2 expression was associated with advanced histological grade, clinical stage and higher TNM classification (P＜0.05). KM analysis showed that patients in the E2F2 high-expression group had worse OS, PFS, and DSS (P=0.019, 0.036, ＜0.001); the ROC curves showed area under the curve (AUC) of E2F2 of predicting 1-, 3- and 5- year survival of ccRCC patients were 0.844, 0.851 and 0.815, respectively. GSEA revealed that the E2F2 low-expression group was enriched in multiple metabolism-related pathways, whereas the E2F2 high-expression group was associated with immune-related pathways. Immune analysis demonstrated that high E2F2 expression was associated with increased immune scores, increased proportion of immune cells, higher tumor mutation burden, and potentially stronger immunotherapy response. IHC results showed that the E2F2 immunoreactivity score in ccRCC tissues was significantly higher than that in adjacent non-tumor tissues (P＜0.05). Functional assays indicated that E2F2 knockdown significantly inhibited the proliferation, colony formation, and migration of ccRCC cells. Conclusion E2F2 is highly expressed in ccRCC and may be involved in tumorigenesis and progression through modulation of the immune microenvironment. Its expression level is closely associated with patient prognosis, and E2F2 has the potential to serve as a prognostic biomarker and immunotherapeutic target in ccRCC.

Objective:To investigate the clinical features of adherent perirenal fat (APF) in patients undergoing laparoscopic adrenal surgery through peritoneal approach, and to analyze its predictors and risk factors, so as to provide reference for clinical diagnosis and treatment.Methods:A total of 86 patients who received transabdominal approach laparoscopic adrenal surgery in the Department of Urology, the Rizhao Hospital of Traditional Chinese Medicine and the First Department of Minimally invasive Urology of Shandong Provincial Hospital from February 2021 to February 2024 were retrospectively selected as the study objects. According to whether patients developed APF during the operation, they were divided into APF group (29 cases) and non-APF group (57 cases). The Mayo Adhesive Probability (MAP) score and preoperative perirenal fat CT density were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in predicting the occurrence of APF. Univariate and multivariate logistic regression models were used to analyze the influencing factors of the occurrence of APF.Results:The MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal gland level) and CT density score of the APF group were higher than those of the non-APF group, with statistical significance (all P<0.05). Age, body mass index (BMI), perirenal fat thickness and the proportion of diabetes mellitus and hyperlipidemia in the APF group were significantly higher than those in the non-APF group, with statistical significance (all P<0.05). The area under ROC curve predicted by MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal level) and CT density score for APF in patients undergoing laparoscopic adrenal surgery were 0.921, 0.655, 0.628, 0.538, and 0.912, respectively. Logistic regression model results showed that high MAP score, high CT density score, old age, high BMI, large perirenal fat thickness, and complicated diabetes were independent risk factors for APF in patients undergoing peritoneal laparoscopic adrenal surgery (all P<0.05). Conclusions:In patients with adrenal tumor treated by peritoneal laparoscopic adrenal surgery, MAP score and CT perirenal fat density examination before operation are beneficial to predict whether APF will occur, which has certain guiding significance for the formulation of surgical plan.

Objective To develop a nomogram-based predictive model for assessing the risk of respiratory distress syndrome(RDS)in premature infants in the high-altitude region of Dali.The predictive performance and clinical applicability of the model will be systematically evaluated to provide evidence-based guidance for the early diagnosis and clinical management of respiratory distress in premature infants.Methods A total of 680 preterm infants admitted to the Dali Maternal and Child Health Hospital between January 2020 and December 2024 were enrolled in the study and randomly divided into a training set(n=476)and a validation set(n=204)at a ratio of 7∶3.Independent predictors were identified through univariate logistic regression and multivariate stepwise regression analyses,and a nomogram model was subsequently developed using R software.The performance of the model,including its discrimination,calibration,stability,and clinical applicability,was evaluated using the receiver operating characteristic curve(ROC),Hosmer-Lemeshow goodness-of-fit test,bootstrap resampling method,and decision curve analysis(DCA).Results The final model incorporated seven independent variables:gestational age,birth weight,Apgar score,blood oxygen saturation,gestational hyperglycemia,prenatal glucocor-ticoid therapy,and maternal history of infection.The areas under the curve(AUCs)for the training and validation sets were 0.88(95%CI:0.84～0.92)and 0.83(95%CI:0.76～0.89),respectively,with all Hosmer-Lemeshow test p-values exceeding 0.05.The bootstrap-corrected AUC was 0.85(95%CI:0.81～0.89).DCA indicated that the model achieved the highest net benefit at a risk threshold range of 10%to 35%.Conclusions This model integrates multiple risk factors associated with the occurrence of RDS in plateau environments,demonstrating robust predictive performance for RDS in preterm infants residing in high-altitude areas such as Dali.It can serve as a valuable tool for risk stratification and clinical decision-making,and may also provide a reference for future multicenter prospective studies.

Objective To develop a nomogram-based predictive model for assessing the risk of respiratory distress syndrome(RDS)in premature infants in the high-altitude region of Dali.The predictive performance and clinical applicability of the model will be systematically evaluated to provide evidence-based guidance for the early diagnosis and clinical management of respiratory distress in premature infants.Methods A total of 680 preterm infants admitted to the Dali Maternal and Child Health Hospital between January 2020 and December 2024 were enrolled in the study and randomly divided into a training set(n=476)and a validation set(n=204)at a ratio of 7∶3.Independent predictors were identified through univariate logistic regression and multivariate stepwise regression analyses,and a nomogram model was subsequently developed using R software.The performance of the model,including its discrimination,calibration,stability,and clinical applicability,was evaluated using the receiver operating characteristic curve(ROC),Hosmer-Lemeshow goodness-of-fit test,bootstrap resampling method,and decision curve analysis(DCA).Results The final model incorporated seven independent variables:gestational age,birth weight,Apgar score,blood oxygen saturation,gestational hyperglycemia,prenatal glucocor-ticoid therapy,and maternal history of infection.The areas under the curve(AUCs)for the training and validation sets were 0.88(95%CI:0.84～0.92)and 0.83(95%CI:0.76～0.89),respectively,with all Hosmer-Lemeshow test p-values exceeding 0.05.The bootstrap-corrected AUC was 0.85(95%CI:0.81～0.89).DCA indicated that the model achieved the highest net benefit at a risk threshold range of 10%to 35%.Conclusions This model integrates multiple risk factors associated with the occurrence of RDS in plateau environments,demonstrating robust predictive performance for RDS in preterm infants residing in high-altitude areas such as Dali.It can serve as a valuable tool for risk stratification and clinical decision-making,and may also provide a reference for future multicenter prospective studies.

Depression is a chronic brain dysfunctional disease mainly due tomood disorders.Currently,the pathogenesis of depression is unclear,and its pathogenesis,pathophysiology and treatment have consistently been a major focus of academic research.This review provides an overview of the role of serum inflammatory factors in the pathogenesis,diagnosis,and treatment of depression.The inflammatory factor pathway provides a theoretical basis for the development of diagnostic and therapeutic methods for depression.It is expected to provide accurate personalized treatment for patients with depression through the treatment of inflammatory factors,improve the treatment outcomest,and reduce the risk of disease progression.

Depression is a chronic brain dysfunctional disease mainly due tomood disorders.Currently,the pathogenesis of depression is unclear,and its pathogenesis,pathophysiology and treatment have consistently been a major focus of academic research.This review provides an overview of the role of serum inflammatory factors in the pathogenesis,diagnosis,and treatment of depression.The inflammatory factor pathway provides a theoretical basis for the development of diagnostic and therapeutic methods for depression.It is expected to provide accurate personalized treatment for patients with depression through the treatment of inflammatory factors,improve the treatment outcomest,and reduce the risk of disease progression.

Objective To investigate the feasibility of a "pericardial lining" modified Bentall procedure for the treatment of patients with aortic root aneurysm. Methods This was a retrospective study that consecutively enrolled patients treated at the Affiliated Suzhou Hospital of Nanjing Medical University, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, and the First People's Hospital of Guangyuan from January 2023 to February 2024. Preoperative clinical data, imaging findings (including echocardiography and CT scans of the aortic root and the entire aorta), details of coronary artery management, surgical outcomes, and postoperative follow-up results were collected. All patients underwent the "pericardial lining" modified Bentall procedure: the aortic valve was replaced, and an autologous pericardial patch was divided into three equal leaflets based on the circumference of the aortic annulus measured by a valve sizer. These leaflets were then sutured to the aortic annulus. Fenestrations were created in two of the pericardial leaflets for anastomosis with the left and right coronary ostia. The pericardial leaflets were sutured to the wall of the aortic sinuses to form an integrated structure, thereby narrowing the sinus portion. A prosthetic vascular graft was anastomosed to the proximal and distal aorta, and no aortic root-to-right atrium shunt was created. Results A total of 5 patients, aged 37 to 68 years, were included. The preoperative Society of Thoracic Surgeons (STS) risk scores ranged from 2.8% to 3.9%. The diameter of the ascending aorta was 40-73 mm, the left ventricular end-diastolic diameter (LVEDD) was 45-71 mm, and the left ventricular ejection fraction (LVEF) was 47%-64%. Intraoperatively, the aortic cross-clamp time ranged from 85 to 180 min, and the cardiopulmonary bypass time ranged from 110 to 302 min. Postoperative follow-up echocardiography revealed that the ascending aortic diameter was 27-35 mm, LVEDD was 39-57 mm, and LVEF was 43%-61%. All surgeries were completed successfully with satisfactory immediate outcomes and no intraoperative complications. During the follow-up period, there was no mortality or reoperation. Conclusion For patients with aortic root aneurysm, the "pericardial lining" modified Bentall procedure yields satisfactory preliminary results, and the technique is demonstrated to be feasible.

BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

The primary role of transfer RNA(tRNA)is to connect a specific amino acid to its 3' end, use its anticodon to match the codon on messenger RNA(mRNA), and deliver the corresponding amino acid to the ribosome for protein synthesis.tRNA exists in two forms: precursor tRNA and mature tRNA.When acted upon by enzymes like Dicer, elaC ribonuclease Z 2(ELAC2), angiopoietin(ANG), and other ribonucleases, tRNA is broken down into tRNA-derived stress-induced RNA(tiRNA)and tRNA-derived fragments(tRF).Recent advancements in RNA sequencing technology have led to increased interest in tiRNA and tRF, shedding light on their roles in various physiological and pathological processes.tRNA-derived small molecules(tsRNA)function similarly to microRNA(miRNA), influencing gene expression and protein synthesis.They show promise as diagnostic markers and potential therapeutic targets for age-related diseases.This review offers a comprehensive analysis of tsRNA classification, biological functions, research advancements, and clinical applications in age-related conditions.