ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 （PINK1）/E3 ubiquitin ligase （Parkin） pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group， sacubitril/valsartan group， and low- and high-dose Shenqi Jianxin Formula groups， with 6 rats in each group. Six other rats were set as the sham surgery group， which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/（kg·d） and 17.64 g/（kg·d）， respectively； the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/（kg·d）； the sham surgery group and the model group were given normal saline at 10 ml/（kg·d） via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were detected， and serum brain natriuretic peptide （BNP） content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction （Rt-qPCR） was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1， p62， and microtubule-associated protein 1 light chain 3 （LC3） in myocardial tissues. ResultsCompared with the sham surgery group， the model group showed significant decreases in LVEF and LVFS levels， an increase in serum BNP content， down-regulated mRNA and protein expressions of PINK1， Parkin and Beclin-1 in cardiac tissues， up-regulated mRNA and protein expressions of p62， as well as significant reductions in LC3B mRNA expression， phosphorylated PTEN-induced kinase 1 （p-PINK1） and phosphorylated E3 ubiquitin ligase （p-Parkin） protein levels， and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ （LC3Ⅱ/LC3Ⅰ） （P＜0.05）. Pathological results revealed obvious myocardial cell edema， necrosis and degeneration， increased disorder of myocardial fiber arrangement， extensive inflammatory cell infiltration， moderate to severe mitochondrial swelling， a few mitochondrial vacuolar changes， and no obvious autophagy in the field of vision in the model group. Compared with the model group， all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group （P＜0.05）. Moreover， the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group （P＜0.05）. In the high-dose Shenqi Jianxin Formula group， myocardial myofibrils were arranged regularly with orderly orientation， the striated structure was clear， and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues， enhance mitochondrial autophagy， and clear dysfunctional mitochondria， thereby improving cardiac function and delaying the progression of CHF.

OBJECTIVES: To systematically evaluate the prevalence and risk factors of non-alcoholic fatty liver disease (NAFLD) in overweight and obese children and adolescents in China. METHODS: Databases including China National Knowledge Infrastructure, Wanfang Data, VIP Database, China Biomedical Literature Database, PubMed, Embase, Web of Science, and Cochrane Library were searched, from database inception to October 2024. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies according to inclusion and exclusion criteria. A Meta analysis was conducted using Stata 16.0 software. RESULTS: A total of 42 studies involving 16 481 overweight and obese children and adolescents were included. The Meta analysis results showed that the prevalence of NAFLD among overweight and obese children in China was 43% (95%CI: 37%-48%). Factors associated with NAFLD included being male (OR=1.61, 95%CI: 1.17-2.04), increased weight (MD=10.33, 95%CI: 9.08-11.57), increased waist circumference (MD=5.49, 95%CI: 3.36-7.62), longer duration of obesity (MD=0.31, 95%CI: 0.02-0.61), higher body mass index (MD=3.11, 95%CI: 2.07-4.16), elevated fasting blood glucose levels (MD=0.17, 95%CI: 0.06-0.29), higher triglyceride levels (MD=0.32, 95%CI: 0.17-0.47), elevated total cholesterol levels (MD=0.15, 95%CI: 0.10-0.21), higher low-density lipoprotein cholesterol levels (MD=0.14, 95%CI: 0.04-0.23), increased alanine aminotransferase levels (MD=24.39, 95%CI: 18.57-30.20), increased aspartate aminotransferase levels (MD=12.49, 95%CI: 9.67-15.32), elevated serum insulin levels (MD=4.47, 95%CI: 2.57-6.36), higher homeostasis model assessment-insulin resistance (MD=0.45, 95%CI: 0.30-0.59), and elevated uric acid levels (MD=55.91, 95%CI: 35.49-76.32) (P<0.05). CONCLUSIONS The prevalence of NAFLD among overweight and obese children and adolescents in China is high. Male gender, increased weight, increased waist circumference, prolonged obesity duration, higher body mass index, dyslipidemia, and elevated levels of fasting blood glucose, liver enzymes, serum insulin, homeostasis model assessment-insulin resistance, and uric acid are potential risk factors for NAFLD in this population.
Humans ; Non-alcoholic Fatty Liver Disease/etiology* ; Risk Factors ; Adolescent ; Child ; Overweight/complications* ; Prevalence ; China/epidemiology* ; Obesity/complications* ; Male ; Female

Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.

Objective:To explore the effects of a tiered-categorized-integrated training model in standardized neurology residency training.Methods:This controlled before-and-after study enrolled 109 residents who rotated in the Department of Neurology of Renji Hospital of Shanghai Jiao Tong University School of Medicine from January 2023 to June 2024. Among them, 43 residents from January to July 2023 were assigned to control group to receive the traditional training model, while 66 residents from August 2023 to June 2024 were assigned to observation group to follow the competency-oriented tiered-categorized-integrated training protocol. In the observation group, the residents were categorized into neurology specialty and non-neurology specialty groups to follow a competency-based hierarchical and progressive training approach with systematical optimization and resource integration in terms of faculty allocation, training activities, and assessment evaluations. The effectiveness of the models was evaluated through semi-annual assessments (for neurology specialty), routine assessments and end-of-rotation assessments (for non-neurology specialty), and 360-degree evaluations. SPSS 26.0 was used to perform chi-square tests and t-tests. Results:The non-neurology specialty residents in the observation group significantly outperformed the control group in the total score of end-of-rotation assessments [(90.93±4.21) vs. (86.08±8.98), P=0.004], theoretical examinations [(16.47±2.47) vs. (13.55±5.34), P=0.003], clinical skills [(9.32±0.47) vs. (9.00±0.58), P=0.004], and case analysis [(86.75±5.95) vs. (82.64±11.20), P=0.047]. The neurology specialty residents in the observation group showed a significantly higher physical examination score than the control group [(87.50±8.66) vs. (75.00±8.17), P=0.040]. Furthermore, in the 360-degree evaluation, the observation group exhibited better performance in certain assessment indicators of core competencies, including professional ability, patient management, professionalism, and communication and cooperation ( P<0.05). Conclusions:The tiered-categorized-integrated training model helps residents to better grasp basic knowledge and skills in rotations, and also enhances their core competencies such as professional ability, patient management, and communication and cooperation. This model provides a replicable practical solution for clinical departments to achieve efficient and precise rotation management within the constraints of limited resources.

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 investigate the alterations in brain functional activity before and after chemotherapy in breast cancer patients with chemotherapy-related cognitive impairment (CRCI) using resting-state functional magnetic resonance imaging (rs-fMRI) and their relations with cognitive impairment.Methods:A prospective observational study was performed; female breast cancer patients with CRCI admitted to Department of Oncology, Affiliated Hospital 6 of Nantong University were recruited, and age- and education level-matched female healthy controls were chosen. Before and one month after chemotherapy, statuses of cognitive function, depression and anxiety in breast cancer patients with CRCI were evaluated by Montreal cognitive assessment (MoCA), functional assessment of cancer therapy-cognitive function (FACT-cog), self-rating depression scale (SDS), and self-rating anxiety scale (SAS); subsequently, conventional MRI and resting-state functional magnetic resonance imaging (rs-fMRI) were conducted. The healthy controls accepted MoCA, SDS, and SAS, followed by conventional MRI and rs-fMRI. Differences in clinical data and amplitude of low-frequency fluctuation (ALFF, rs-fMRI brain spontaneous neural activity index) were compared between breast cancer patients with CRCI before chemotherapy and healthy controls, and in the breast cancer patients with CRCI between before and after chemotherapy. Taking the brain regions with significant differences in ALFF before and after chemotherapy in breast cancer patients with CRCI as seed points, the difference in whole-brain functional connectivity (FC) before and after chemotherapy was compared in breast cancer patients with CRCI. Pearson or Spearman correlation tests were used to analyze the correlations of ALFF and FC in brain regions with significant differences in ALFF with cognitive function scores in breast cancer patients with CRCI.Results:(1) A total of 22 breast cancer patients with CRCI and 22 healthy controls were enrolled. Compared with the healthy controls, the breast cancer patients with CRCI before chemotherapy had significantly higher SDS and SAS scores ( P<0.05). Compared with breast cancer patients with CRCI before chemotherapy, the breast cancer patients with CRCI after chemotherapy had significantly lower MoCA, FACT-cog-perceived cognitive impairment, FACT-cog-comment from others on cognitive function, and FACT-cog-perceived cognitive ability ( P<0.05). (2) Compared with those before chemotherapy, breast cancer patients with CRCI after chemotherapy exhibited significantly increased ALFF in the right precuneus, right middle occipital gyrus, and left superior frontal gyrus, while statistically decreased FC in the right middle occipital gyrus-left middle temporal gyrus, right precentral gyrus-right middle temporal gyrus, and left superior frontal gyrus-left fusiform gyrus ( P<0.05). (3) ALFF in the right precentral gyrus in breast cancer patients with CRCI after chemotherapy was negatively correlated with difference value of FACT-cog before and after chemotherapy ( r=-0.497, P=0.018) and difference value of PCA before and after chemotherapy ( r s=-0.436, P=0.042); FC in the left superior frontal gyrus-left fusiform gyrus was positively correlated with score of FACT-cog-perceived cognitive impairment ( r=0.621, P=0.002). Conclusion:Chemotherapy induces compensatory enhancement of spontaneous neural activity in multiple brain regions in breast cancer patients with CRCI, accompanied by FC disruption at specific brain areas, which are associated with cognitive impairment.

Pancreaticoduodenectomy (PD) stands as one of the most challenging landmark procedures in general surgery. Postoperative pancreatic fistula (POPF), a common complication following PD, predisposes patients to secondary pathologies and remains difficult to avoid. Reducing its incidence and mitigating its impact have become focal points in pancreatic surgical research. This article comprehensively reviews domestic and international literature to systematically analyze key factors influencing POPF across three phases: preoperative, intraoperative, and postoperative management. By gaining deeper insights into the pathogenesis of POPF, this review aims to enhance clinical understanding among healthcare professionals, facilitate the implementation of preventive strategies, and offer novel perspectives for minimizing postoperative fistula risks.

Chronic myeloid leukemia (CML) is a malignant hematologic disorder caused by abnormal proliferation of hematopoietic stem cells. In recent years, while the application of tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis of CML patients through in-depth exploration of pathogenesis of CML and advancements in targeted therapies, some patients still face challenges including drug resistance, disease relapse, and failure to achieve treatment-free remission. Imunotherapy, as a complementary or alternative strategy, holds significant potential for overcoming these limitations, and has gradually emerged as a critical research focus in CML treatment. This review aims to summarize the current research status and latest advances in immunotherapy for CML.