OBJECTIVES: To investigate the expression patterns and prognostic value of lipid metabolism-related genes in breast cancer. METHODS: RNA sequencing data and clinical information were obtained from The Cancer Genome Atlas breast cancer (TCGA-BRCA) dataset, including 1100 breast cancer tissue samples (18 paired with adjacent tissues) and 112 normal breast tissue samples. Differentially expressed lipid metabolism-related genes were screened from a predefined set of 2043 genes using Bioconductor in R, with a false discovery rate <0.05 and |log2(fold change)|>2. Eligible samples were randomly divided into a training cohort (n=651) and a validation cohort (n=431) at a 6∶4 ratio. Prognostic lipid metabolism-related genes were identified using univariate Cox regression (P<0.005) and further refined via LASSO regression. A risk score model was constructed using multivariate Cox regression, and patients were stratified into high- and low-risk groups based on the median risk score. The model's performance was evaluated using Kaplan-Meier survival analysis with the log-rank test and time-dependent receiver operating characteristic (ROC) curves. A nomogram integrating age, TNM stage, clinical grade, and risk score was developed and validated using calibration curves and the concordance index. Immune cell infiltration was quantified using an immune scoring algorithm, and weighted gene co-expression network analysis (WGCNA) was applied to identify key modules associated with immune cell infiltration. Finally, to validate the function of the key gene ALDH2, small interfering RNA targeting ALDH2 was transfected into breast cancer cells, and its effects on invasion and migration were assessed using Transwell invasion and wound healing assays. RESULTS: A total of 185 differentially expressed lipid metabolism-related genes were identified. Univariate Cox and LASSO regression analyses identified three genes-ALDH2, CYP21A2, and IL24-which were incorporated into the multivariate Cox model. The prognostic model based on these genes demonstrated good predictive performance in both cohorts: patients in the high-risk group had significantly shorter overall survival (P<0.01), and the area under the ROC curve for predicting 1-, 3-, and 5-year survival rates was above 0.64. Analysis of the tumor microenvironment revealed an immunosuppressive phenotype in the high-risk group, characterized by reduced infiltration of several anti-tumor immune cells and downregulation of key immune checkpoint molecules such as PDCD1 and CTLA4. WGCNA suggested an association between ALDH2 and immune cell infiltration. Functional experi-ments confirmed that ALDH2 knockdown significantly enhanced the migration and invasion abilities of breast cancer cells. CONCLUSIONS This study established and validated a pro-gnostic model for breast cancer based on lipid metabolism-related genes. It revealed that low ALDH2 expression is closely associated with poor prognosis and immunosuppression, suggesting its potential as a prognostic biomarker and therapeutic target in breast cancer.

Objective:To investigate the clinical characteristics of non-typhoidal Salmonella（NTS）enteritis in children and the drug resistance of NTS strains.Methods:The clinical data of 138 children who were hospitalized in Children's Hospital Affiliated to Xi'an Jiaotong University from 2022 to 2023 with diarrhea as the main complaint and NTS detected in stool culture were analyzed retrospectively, and the clinical characteristics and drug resistance were summarized.Results:Among 138 children with NTS enteritis，89 were males and 49 were females，with a male-to-female sex ratio of 1.81∶1 and an average age of 1.9（1.0,3.6）years，with a high incidence rate in June,July and August.Seventeen（12.31%）cases had a history of suspected unclean diet before illness.All the children had diarrhea symptoms with changes in fecal frequency and character，including 74 cases of pus and bloody stool，119 cases of mucus stool，and 70 cases of watery stool.One hundred and twenty-five（90.57%）cases had fever.Among 138 cases of fecal culture,there were 47 (34.05%) strains of Salmonella typhimurium,36(26.09%) strains of Salmonella enteritidis,and 55(39.85%) strains of other serotypes of Salmonella .One hundred and twenty-two（88.40%）NTS strains were resistant to more than one antimicrobial agent，and 29（21.01 %）were multi-drug resistant.The resistance rates to ampicillin，ampicillin/sulbactam，ceftriaxone，trimethoprim/sulfamethazole，ceftazidime，cefepime and piperacillin/tazobactam were 73.91%，71.01%，29.71%，29.71%，23.19%，11.59%，and 3.62%，respectively.All strains were sensitive to carbapenem antibiotics（meropenem，imipenem，and ertapenem）.The drug resistance rates of Salmonella typhimurium to ceftazidime and trimethoprim/sulfamethoxazole were higher than those of Salmonella enteritidis（38.30% vs 8.33%），the difference was statistically significant ( P < 0.05). Conclusion:Infants and young children are the high-incidence group of NTS enteritis，with the peak incidence period being from June to August each year，manifested by mucus-pus-blood stools, abdominal pain, vomiting，fever and other symptoms.Reasonable selection of antibiotics in time according to the local epidemic strains,changes of antimicrobial resistance and the results of drug sensitivity test of strains can effectively resist infection and reduce the production of drug-resistant beads.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Objective: To evaluate the clinical efficacy of a novel autologous blood recovery device during the weaning process from extracorporeal membrane oxygenation (ECMO). Methods: A total of 16 patients who received ECMO support and underwent blood recovery during the weaning process from January 2022 to September 2024 at our hospital were included in the experimental group. In contrast, 58 patients who did not receive blood recovery during the weaning process were assigned to the control group. Transfusion components, costs, and changes in routine blood tests and coagulation functions were compared between the two groups from the day of weaning until 48 hours post-weaning. Results: Significant differences were observed in the volumes of red blood cell transfusions, plasma transfusions, and transfusion costs between the two groups from the day of weaning to 48 hours post-weaning (P<0.05). Additionally, in the experimental group, significant differences were noted in hemoglobin (Hb), platelet (Plt), and activated partial thromboplastin time (APTT) results when comparing values before and after extubation (P<0.05). Conclusion: The application of a novel autologous blood recovery device during ECMO weaning reduces patient costs, minimizes wastage of autologous blood, decreases reliance on exogenous blood transfusions, and mitigates the risks associated with allogeneic blood transfusion. This approach merits further promotion for clinical use.

Breast cancer is the most prevalent malignant tumor that poses a threat to women's health in China,with incidence and mortality rates persistently increasing.Given this critical situation,there is an urgent need to optimize therapeutic options through basic translational research to address current treatment challenges.This article provided a comprehensive overview of the significant advancements in fundamental translational breast cancer research in China over the past five years,aiming to provide a scientific basis and new directions for precision treatment of breast cancer.This research encompasses a range of subjects,including molecular typing,biomarker identification,exploration of drug resistance mechanisms,optimization of precision treatment strategies,and identification of new targets in breast cancer.In the domain of molecular typing,researchers have revealed substantial disparities in treatment responses among distinct subtypes of breast cancer through in-depth analysis.This has led to the proposal of specific therapeutic strategies for each subtype,thereby establishing a robust theoretical foundation for individualized treatment approaches.The identification of biomarkers plays a pivotal role in selecting appropriate treatment options for patients.Recent research advancements have demonstrated the potential of liquid biopsy and proteomics technologies in uncovering promising biomarkers,offering novel prospects for the early diagnosis and prognostic assessment of breast cancer.In the investigation of resistance mechanisms,researchers have elucidated the molecular underpinnings of resistance to endocrine therapy and human epidermal growth factor receptor 2(HER2)-targeted therapy and proposed potential strategies to overcome resistance.This has paved the way for novel approaches to enhance therapeutic efficacy.In the context of immunotherapy and targeted therapies,the discernment of novel targets and biomarkers has facilitated novel perspectives on breast cancer treatment.Based on advanced comprehension of tumor heterogeneity,researchers constantly optimize precision treatment strategies through multiomics analysis,thus offering patients with breast cancer enhanced personalized treatment options.Concurrently,the implementation of novel technologies has been instrumental in facilitating the advancement of precision treatment for breast cancer.For instance,the application of artificial intelligence technology has demonstrated considerable potential in the early screening,diagnosis,efficacy assessment and prognosis prediction of breast cancer.Conversely,the advent of innovative drug delivery systems facilitated by nanotechnology has led to enhanced targeting and efficacy of pharmaceutical agents.Furthermore,research into hydrogel patch technology and tumor vaccines has yielded novel strategies for the treatment of breast cancer.Overall,China has accomplished remarkable achievements in the field of basic translational research on breast cancer.These findings not only enhance our understanding of the molecular mechanisms of breast cancer,but also provide new directions and hope for the development of future therapeutic strategies.With the advancement of multidisciplinary integration and the application of new emerging technologies,precision therapy is expected to provide more benefits to breast cancer patients.

BACKGROUND:Total flavonoids from Sophora flavescens have a variety of pharmacological effects,including anti-inflammatory,immunomodulatory,antioxidant,and anti-hepatic injury,but the therapeutic effects and mechanisms in non-alcoholic fatty liver disease are not clear.OBJECTIVE:To reveal the mechanism of total flavonoids from Sophora flavescens in the treatment of non-alcoholic fatty liver disease using bioinformatics,network pharmacology and zebrafish experimental validation.METHODS:A zebrafish model of non-alcoholic fatty liver disease was constructed to observe lipid accumulation,pathomorphologic changes,and expression of inflammatory genes in the liver of zebrafish after treatment with total flavonoids from Sophora flavescens.The active ingredients of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease-related targets were obtained from TCMSP,Swiss Target Prediction,and Bat-man databases.STRING was used to perform protein-protein interaction network analysis,GO functional enrichment and KEGG pathway enrichment analysis.Based on the GSE33814 dataset,the differentially expressed genes of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease intersection targets were screened out.Correlation analysis and receiver operating characteristic curve were performed using R4.3.2 software.Core genes were verified by the validation set GSE89632.RT-qPCR and western blot assays were performed to verify the expression of core pathway-related genes and proteins.RESULTS AND CONCLUSION:(1)Total flavonoids from Sophora flavescens could improve lipid accumulation in the liver of zebrafish with non-alcoholic fatty liver disease,significantly inhibited the elevation of lipid and aminotransferase levels in zebrafish(P<0.05),and regulated the expression of genes related to inflammation and lipid metabolism.(2)A total of 168 common targets were obtained using the network pharmacology,and top 10 core genes,identified by Cytoscape topology analysis,were HSP90AA1,STAT3,PIK3R1,MAPK1,AKT1,RXRA,PIK3CA,EGFR,JAK2,and ESR1.GO and KEGG analysis pathways mainly included insulin resistance,lipids,and atherosclerosis.There were a total of 59 differentially expressed genes after intersection of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease targets.The receiver operating characteristic curve and validation set analyses yielded six core targets that were significantly different between healthy individuals and patients with non-alcoholic fatty liver disease(P<0.01).(3)RT-PCR and western blot results verified that total flavonoids from Sophora flavescens inhibited the activation of the JAK2/STAT3 signaling pathway in zebrafish.To conclude,total flavonoids from Sophora flavescens may alleviate the inflammatory response through the JAK2/STAT3 signaling pathway,thus inhibiting lipid accumulation and improving non-alcoholic fatty liver disease.

Objective:To investigate the association between prenatal environmental factors and attention defi-cit hyperactivity disorder(ADHD)and its symptom severity in children.Methods:Based on the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)diagnosis criteria,1 156 children with ADHD and 289 normal control children were included in this study.ADHD diagnoses were established using the Clinical Diag-nostic Interview Scale,core symptoms were assessed with the ADHD Rating Scale,and information on prenatal ex-posures were collected via self-developed questionnaires.Results:Maternal stress during pregnancy was associated with increased risk factor of ADHD in children(OR=1.22,P＜0.01).Among children with ADHD,preconception paternal alcohol consumption was positively associated with hyperactivity/impulsivity symptoms(β=0.08,P＜0.05),and maternal smoking during pregnancy was positively associated with total symptoms(β=0.07-0.09,P＜0.05).Conclusion:Maternal stress during pregnancy may increase the risk factor of ADHD in children.Both pre-conception paternal alcohol consumption and maternal smoking during pregnancy may be associated with increased ADHD symptom severity in children.

Objective:To evaluate the efficacy of transumbilical single-port robotic-assisted laparoscopic surgery for congenital choledochal cysts in children.Methods:Clinical data of 13 children with congenital choledochal cysts undergoing surgery at the Provincial Hospital of Fuzhou University from January 2024 to June 2024 were retrospectively analyzed, including 4 males and 9 females, aged 48 (24, 60) months. All children underwent transumbilical single-port robotic-assisted laparoscopic radical resection of congenital choledochal cyst with common hepatic duct jejunum Roun-en-Y anastomosis by the same surgeon. The efficacy of this technique was evaluated by surgical safety indicators such as operation time and intra-operative blood loss, as well as indicators of the postoperative scar assessment scale (OSAS).Results:All surgeries were successfully performed without conversion to open surgery. The operation time was (200±22) min. The blood loss was (8.07±2.56) ml without intraoperative blood transfusion. The time to start water feeding was (2.76±0.83) d and the time to start liquid diet was (3.92±1.12) d. The postoperative hospital stay was (7.00±3.37) d and the postoperative follow-up time was (5.38±2.06) months. No postoperative complications such as bile reflux gastritis and cholangitis were seen in patients. No dilatation of the common hepatic duct or intrahepatic bile ducts were observed at three months postoperatively. There were good indicators of satisfaction with the appearance of wounds as assessed by OSAS.Conclusion:Transumbilical single-port robotic-assisted laparoscopic surgery could be safe and effective for congenital choledochal cysts in children.