[摘 要] 目的：明确线粒体DNA（mtDNA）部分缺失对结肠上皮细胞NCM460的影响。方法：通过溴化乙锭（EB）诱导建立mtDNA部分缺失细胞模型（mtDNA-reduced）及恢复模型（reverted），采用CCK-8、活性氧（ROS）及线粒体膜电位检测评估线粒体功能，通过葡萄糖、乳酸及糖酵解关键酶活性检测评估代谢表型，通过Transwell实验及WB法检测细胞侵袭及上皮-间质转化（EMT），通过polyHEMA包被培养检测失巢凋亡抵抗能力；检测PI3K/Akt/mTOR信号通路及程序性死亡配体1（PD-L1）表达，并通过PI3K抑制剂LY294002验证。结果：GEPIA数据库分析显示mtDNA编码基因在结直肠癌中低表达（P < 0.05）；组织芯片显示COX1蛋白在正常结肠组织高表达，在癌组织中低表达（P < 0.05）。mtDNA-reduced NCM460细胞线粒体功能受损（生长速率下降、ROS生成减少、线粒体膜电位降低，P < 0.05），呈现Warburg效应（葡萄糖摄取增加、乳酸分泌增多、糖酵解关键酶活性增强，P < 0.05），侵袭能力增强（P < 0.05）且发生EMT，并抵抗失巢凋亡（P < 0.05）。该细胞PI3K/Akt/mTOR通路激活且PD-L1表达上调；经LY294002处理后，葡萄糖含量有降低趋势（P > 0.05）、细胞活性下降（P < 0.05），PD-L1表达下调（P < 0.05）。结论：结肠上皮细胞NCM460中mtDNA部分缺失可诱导其恶性转化及免疫逃逸。

Hormone receptor (HR)-positive/HER2-negative early breast cancer is the most common subtype of breast cancer, and endocrine therapy serves as the cornerstone of adjuvant treatment. In recent years, with the publication of key clinical trials such as SOFT, TEXT, and monarchE, and breakthroughs in novel agents studies like lidERA, the endocrine therapy strategy for HR-positive/HER2-negative early breast cancer has evolved toward increased precision and intensity. This article systematically reviews the latest advances in endocrine therapy, focusing on the consolidation of ovarian function suppression as a standard for high-risk premenopausal patients with updated follow-up evidence, the benefit-risk assessment of extended endocrine therapy, and the current application and interdrug differences of CDK4/6 inhibitors in the adjuvant setting. This manuscript also addresses existing challenges, including optimizing treatment-related quality of life and precisely identifying beneficiary populations, and briefly introduces the clinical trial progress of novel agents, such as oral selective estrogen receptor degraders. Furthermore, it outlines evidence-based strategies for ovarian protection during chemotherapy and fertility preservation for young patients. This review aims to provide clinicians with a comprehensive perspective, balancing the pursuit of maximal efficacy with patients′ long-term quality of life and individualized needs.

ObjectiveTo investigate the efficacy and safety of Shuganning injection in the treatment of liver injury by observing the clinical outcome of patients with liver injury after treatment with Shuganning injection and comparing it with reduced glutathione （GSH）. MethodsThis study was conducted among 175 patients with liver injury who attended 6 hospitals in China （Beijing YouAn Hospital， Capital Medical University； Nanyang First People’s Hospital； The Second Affiliated Hospital of Xi’an Jiaotong University； The Fifth Medical Center of Chinese PLA General Hospital； The Third Hospital of Hebei Medical University； The Affiliated Hospital of Guizhou Medical University） from April 25， 2019 to February 28， 2022. The patients were divided into experimental group （89 patients treated with Shuganning injection） and control group （86 patients treated with GSH）， and the course of treatment was 4 weeks for both groups. Related indicators were recorded before treatment， after treatment， and after drug withdrawal for 8 weeks， including liver function parameters， blood biochemical parameters， blood lipids， coagulation profiles， liver fibrosis markers， traditional Chinese medicine （TCM） syndrome score， and ultrasound findings， as well as adverse events during treatment. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Wilcoxon signed-rank test was used for comparison of observation indicators before treatment， at week 4 of treatment， and after drug withdrawal for 8 weeks. When the efficacy evaluation of TCM syndromes was used as the outcome， a pooled analysis was performed for the effective cases and the markedly effective cases， and a Logistic regression model was used to calculate the odds ratio （OR） and its 95%CI. ResultsAfter 4 weeks of treatment with Shuganning injection， the patients showed significant reductions in TCM syndrome score （P<0.001） and the levels of aspartate aminotransferase， alanine aminotransferase， total bilirubin， and direct bilirubin （all P<0.001） and a significant increase in the level of albumin （P=0.002）， and these significant improvements persisted after drug withdrawal for 8 weeks. Furthermore， compared with the control group， the experimental group had a significantly higher proportion of patients assessed as effective or markedly effective cases （48.31% vs 32.56%， P=0.033）. Compared with the control group， the experimental group had a significantly greater change in TCM syndrome score at weeks 1-4 of treatment and after drug withdrawal for 8 weeks （P<0.05）. At week 4 of treatment， the experimental group had a significantly greater reduction in alanine aminotransferase than the control group （P<0.05）， and at week 8 after drug withdrawal， the experimental group had a significantly greater reduction in alanine aminotransferase and aspartate aminotransferase than the control group （all P<0.05）. One patient in the experimental group （1.12%） experienced an adverse event， which was determined to be associated with the progression of viral hepatitis. ConclusionShuganning injection can effectively improve liver injury， with good long-term efficacy and a low incidence rate of adverse reactions.

Objective To investigate the expression characteristics of c-MET protein in colorectal cancer (CRC) and its associations with clinicopathological parameters, MET gene amplification status, and prognosis, and to evaluate the concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) detection strategies, thereby providing evidence for patient selection for MET-targeted therapy. Methods A total of 193 formalin-fixed paraffin-embedded (FFPE) tissue samples from CRC patients were collected. Immunohistochemistry (IHC) was used to detect c-MET protein expression, and fluorescence in situ hybridization (FISH) was performed to evaluate MET gene amplification status. The associations between c-MET protein expression and clinicopathological characteristics, including KRAS, NRAS, and BRAF mutation status, as well as progression-free survival (PFS), were analyzed. The concordance between IHC and FISH detection results was also evaluated. Results c-MET protein expression was significantly higher in tumor tissues than in adjacent normal tissues (P<0.05). Significant differences in c-MET expression were observed between primary tumors and liver or peritoneal/pelvic metastatic lesions (P<0.05). The proportion of high c-MET expression was significantly higher in KRAS-mutant patients than in KRAS wild-type patients (41.38% vs. 16.92%, P<0.05). The MET gene amplification rate was 8.29% (16/193), including clustered or diffuse amplification in 1.55% (3/193) and heterogeneous amplification in 6.74% (13/193). No MET exon 14 skipping mutation or amplification was detected by next-generation sequencing (NGS). Using an IHC H-Score≥150 as the threshold, the positive percent agreement (PPA) between IHC-detected c-MET protein expression and FISH-detected MET gene amplification was 100%. All clustered MET amplification regions exhibited diffuse strong c-MET expression (IHC 3+). No statistically significant association was observed between c-MET expression level and PFS (P>0.05). Conclusion High c-MET expression may represent a potential therapeutic target for KRAS-mutant CRC patients. An H-Score ≥150 is recommended as the initial screening threshold to rapidly identify patients suitable for MET-targeted therapy, with FISH testing when necessary. Diffuse strong c-MET expression (IHC 3+) shows high concordance with clustered MET gene amplification.

Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.

Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.

In order to further standardize the vaccination of kidney transplant candidates and recipients in China, the Branch of Organ Transplantation of Chinese Medical Association has organized experts in kidney transplantation and infectious diseases. Based on the "Vaccination of Solid Organ Transplant Candidates and Recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice", and in combination with the clinical reality of infectious diseases and vaccination after organ transplantation in China, as well as referring to relevant recommendations from home and abroad in recent years, these guidelines are formulated from aspects such as epidemiology, types of vaccines, vaccination principles, target population, and specific vaccine administration. The "Guidelines for Vaccination of Kidney Transplant Candidates and Recipients in China" aims to provide theoretical reference for medical workers in the field of kidney transplantation in China, regarding the vaccination of kidney transplant candidates and recipients. It is expected to better guide the vaccination of kidney transplant candidates and recipients, reduce the risk of postoperative infection, and improve survival outcomes.

Erectile dysfunction (ED) is prevalent among men, but its relationship with dietary habits is uncertain. The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1, 2022, via PubMed, Web of Science, and EMBASE databases. The data compiled included author details; publication dates, countries, treatments, patient numbers, ages, follow-ups, and clinical trial outcomes, such as ED cases, odds ratios (ORs), confidence intervals (CIs), and International Index of Erectile Function-5 (IIEF-5) scores with means and standard deviations. An analysis of 14 studies with 27 389 participants revealed that plant-based diets (OR = 0.71, 95% CI: 0.66-0.75; P < 0.00001), low-fat diets (OR = 0.27, 95% CI: 0.13-0.53; P = 0.0002), and alternative diets such as intermittent fasting and organic diets (OR = 0.54, 95% CI: 0.36-0.80; P = 0.002) significantly reduced ED risk. High-protein low-fat diets (hazard ratio [HR] = 1.38, 95% CI: 1.12-1.64; P < 0.00001) and high-carb low-fat diets (HR = 0.79, 95% CI: 0.55-1.04; P < 0.00001) improved IIEF-5 scores. Combined diet and exercise interventions decreased the likelihood of ED (OR = 0.49, 95% CI: 0.28-0.85; P = 0.01) and increased the IIEF-5 score (OR = 3.40, 95% CI: 1.69-5.11; P < 0.0001). Diets abundant in fruits and vegetables (OR = 0.97, 95% CI: 0.96-0.98; P < 0.00001) and nuts (OR = 0.54, 95% CI: 0.37-0.80; P = 0.002) were also correlated with lower ED risk. Our meta-analysis underscores a strong dietary-ED association, suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
Humans ; Male ; Erectile Dysfunction/epidemiology* ; Diet ; Diet, Fat-Restricted ; Feeding Behavior ; Penile Erection/physiology* ; Diet, Vegetarian

OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant