Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

In the era of evidence-based medicine， the progress of medical science and technology has enriched medical diagnostic tools and treatment methods， but it has also led to the loss of medical warmth and the alienation of the doctor-patient relationships. William Osler emphasized that while medical technology advances， attention should also be paid to the practice of narrative medicine and the development of physician’s narrative literacy. The view of the physician he advocated reminds us that the core of medicine still lies in the narrative connection between doctors and patients， as well as a deep understanding of human nature. By exploring the relationship between Osler’s view of the physician and narrative medicine as well as physician’s narrative literacy， this paper analyzed the methods of cultivating physician’s narrative literacy， providing references for modern medical education and practice， and assisting in the harmony and unity of science and technology and humanity.

Objective:To investigate the incidence, risk factors, and outcomes of falls among the elderly community population in Beijing.Methods:A cross-sectional survey was conducted using stratified multistage random sampling to select urban and rural residents aged 65 years and older in Beijing. Mortality data was collected after the baseline survey for 5 years. The incidence of falls was weighted based on the composition ratios of age and gender from the 2010 Nation-wide Population Census of Beijing. A logistic regression model was used to analyze the impacts of demographic sociology of common chronic diseases on fall occurrence. The Cox proportional hazards regression model was used to analyze the fall and 5-year survival association.Results:A total of 2 968 participants completed the questionnaire, at cross-sectional survey, with an average age of (73.2±6.0) years, and 1 581 (53.8%) participants were female. Three hundred and sixty-one individuals experienced a fall within the past year. Among those who fell, 64 (17.7%) fell twice, and 95 (26.6%) fell three or more times. Of them, 14.4% (52) had post-fall fractures, with the wrist, knee, and hip being the most common fracture sites, accounting for 25.0%, 17.3%, and 15.4%, respectively. The weighted fall incidence was 12.4% (95% CI: 11.2%-13.5%). Aging, being female, and living in rural areas were more likely to fall. Logistic regression analysis showed that after adjusting for age, gender, and urban-rural status, the risk of falls for those living alone ( OR=1.48, 95% CI: 1.08-2.04) or living with children/grandchildren ( OR=1.51, 95% CI: 1.15-1.97) were significantly higher than those living with their spouse. In addition, the risk of falls was elevated significantly among the elderly with hypertension, diabetes, stroke, dementia, depression status, urinary incontinence, arthritis, insomnia, vision, and hearing loss, dependence on activities of daily living (ADL), general and poor self-rated health (SRH). The Cox proportional hazard regression model revealed that the 5-year risk of death increased by 65% ( HR=1.65, 95% CI: 1.29-2.11) for those who experienced a fall, which increased with fall frequency. This elevated risk persisted after adjusting for chronic conditions, ADL, and SRH. Conclusions:Ageing, female, living in rural regions, having common chronic diseases, dependence on ADL, general and poor SRH, living alone or living with children/grandchildren were associated with the elevated fall risk. The occurrence of fall was seasonal. The most common short-term adverse consequence after a fall was fractures, while the long-term effect was an increased risk of death.

Objective:To investigate the clinical characteristics and genetic variations of patients with aminoacylase-1 deficiency (ACY1D) caused by ACY1 gene mutations, in order to enhance clinicians′ understanding of this rare disease. Methods:Clinical and genetic data of a child with ACY1D admitted to Sir Run Run Hospital, Nanjing Medical University in December 2021 were collected. Using "aminoacylase-1 deficiency" "aminoacylase-1 gene" " ACY1" and "ACY1D" as keywords, relevant cases of ACY1 gene mutations were searched in CNKI, Wanfang Data Knowledge Service Platform, OMIM, and PubMed databases until February 2025. The clinical characteristics and types of genetic variations of previously reported ACY1D patients were summarized and analyzed. Results:The patient was an 8-year and 4-month-old boy. Clinical manifestations included growth retardation, ataxia, and focal epileptic seizures. Increased excretion of various N-acetylamino acids was observed in the urine. Cranial magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing results showed a compound heterozygous mutation in the ACY1 gene: c.1063-1G>A (IVS14-1G>A) and c.170G>A (p.G57D) (reference transcript NM_000666.2), with c.170G>A (p.G57D) being a novel mutation. Family validation results showed that the c.1063-1G>A (IVS14-1G>A) mutation originated from his mother, and the c.170G>A (p.G57D) mutation originated from his father. By literature review 11 English articles were retrieved reporting 18 ACY1D patients, along with the child in this study, totaling 19 cases, with an onset age ranging from 1 week to 4 years and 6 months. Among them, 13/19 patients showed growth retardation, 9/19 patients had language disorders, 8/19 patients had intellectual disabilities, 7/19 patients had ataxia and low muscle tone, 6/19 patients had epilepsy and febrile convulsions, and 3/19 patients had irritability, autism, and muscle weakness. Genetic testing results indicated various types of mutations in the ACY1 gene, including missense, splicing, and frameshift mutations. Conclusions:ACY1D is an autosomal recessive genetic disease caused by ACY1 gene mutations, which is relatively rare in China. The main clinical manifestations include growth retardation, intellectual and language disorders. The c.170G>A heterozygous mutation is a newly discovered variant site, expanding the mutation spectrum of the ACY1 gene. Screening for ACY1 gene variations can aid in achieving a definitive diagnosis..

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

OBJECTIVES: To explore the effects of exogenous trigger (hCG/GnRHa) versus endogenous LH surge in natural cycle IVF/ICSI (NC-IVF/ICSI) for patients with diminished ovarian reserve (DOR). METHODS: A retrospective analysis was conducted on 1,118 NC-IVF/ICSI cycles from two reproductive centers between 2013 and 2024. Propensity score matching (PSM) and multivariate logistic regression were used to adjust for confounding factors. The trigger-day hormone threshold was determined using receiver operating characteristic (ROC) curve analysis. Outcome measures included oocyte retrieval rate, 2PN fertilization rate, clinical available embryo rate, high-quality embryo rate, fresh cycle clinical pregnancy rate (CPR), and live birth rate (LBR). RESULTS: After adjusting for confounders via PSM and logistic regression, the exogenous trigger group demonstrated significantly better outcomes across all the evaluated parameters (oocyte retrieval rate, 2PN fertilization rate, transferable embryo rate, high-quality embryo rate, fresh cycle CPR, and LBR) than the endogenous LH surge group (P<0.05). Age-stratified analysis revealed that for the entire cohort, exogenous triggering significantly increased the number of transferable embryos and high-quality embryos (P<0.001). In the 35-39 years old subgroup, exogenous triggering showed significant advantages in oocyte yield, high-quality embryo rate, CPR, and LBR (P<0.05) and resulted in the most pronounced improvement in LBR (OR=6.25, 95% CI: 1.34-29.23). ROC analysis established a decision-day LH threshold of 19.055 mIU/mL (AUC=0.945, specificity=93.3%) for precise stratification of the clinical pathways. CONCLUSIONS For DOR patients undergoing NC-IVF/ICSI, exogenous triggering comprehensively improves the treatment outcomes, particularly providing significant live birth benefits for women aged 35-40 years. An individualized protocol incorporating the LH threshold (19.055 mIU/mL) effectively enhances embryonic developmental potential and live birth rates.
Humans ; Female ; Ovarian Reserve ; Pregnancy ; Propensity Score ; Retrospective Studies ; Fertilization in Vitro ; Sperm Injections, Intracytoplasmic ; Chorionic Gonadotropin ; Pregnancy Rate ; Logistic Models ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone ; Adult ; Oocyte Retrieval

Objective:To explore the lifestyle pattern of the physical examination population and analyze its association with metabolic associated fatty liver disease (MAFLD).Methods:This was a cross-sectional study. Based on the data of 196 515 physical examination individuals from the Health Management Center of the Third Xiangya Hospital of Central South University from January 2016 to December 2020, the subjects were grouped and characterized by principal component analysis and cluster analysis. Among them, 137 277 cases with MAFLD diagnosis information were included in the association analysis between lifestyle pattern and MAFLD. The differences in lifestyle pattern choice among different age, sex, education level, marital status, occupational category and medical insurance type and their differences with the risk of MAFLD were analyzed. The generalized linear mixed model was used to control confounding factors and then association analysis was conducted.Results:There were 6 types of lifestyle patterns in the physical examination population, which were respectively: indulgent type-both physical and mental damage, remedial type-excessive diet, giving type-unique intensity, comfortable type-natural health, heavy smoking type-sedentary injury, heavy drinking type-attempting to make up, accounting for 7.29%, 9.62%, 7.43%, 52.16%, 9.77%, 13.73% in the population. Among them, the male lifestyle pattern was mainly the indulgent type, the remedial type, the heavy smoking type and the heavy drinking type, showing the characteristics of unhealthy lifestyle pattern; Women tended to have healthier lifestyle patterns. After association analysis with MAFLD, it was found that the prevalence of MAFLD was more than 50% in the people who belonged to the indulgent type, remedial type, the heavy smoking type and the heavy drinking type (53.62%, 57.06%, 51.25% and 50.50%, respectively), and the prevalence of MAFLD in the giving type group was 40.17%. The risk of MAFLD in comfortable group was relatively low (28.25%), and the difference in risk of MAFLD among all modes was statistically significant after controlling for confounding factors ( P<0.001). Conclusion:According to cluster mining, there are 6 types of lifestyle patterns in the physical examination population, and the healthier lifestyle pattern has a lower risk of MAFLD.

Objective:To analyze the differences in clinicopathological features between non-elderly and elderly patients with melanoma, and to identify risk factors for prognosis in elderly patients with melanoma.Methods:A retrospective analysis was conducted on clinical and pathological data collected from non-elderly (aged < 60 years) and elderly (aged ≥ 60 years) patients with melanoma, who were confirmedly diagnosed according to clinical manifestations and histopathological findings at the People's Hospital of Xinjiang Uygur Autonomous Region from January 2008 to December 2023. The differences in clinical and pathological characteristics between the two groups were analyzed using the chi-square test and Wilcoxon rank-sum test. Survival curves were estimated using the Kaplan-Meier method and log-rank test. The relationship between clinicopathological variables and overall survival was analyzed using a Cox regression model.Results:A total of 233 patients with cutaneous melanoma were included, with the age being 60.3 ± 14.7 years, and the number of patients was highest in the age group of 60 - 69 years. There were 102 cases (43.8%) in the < 60 years old group and 131 cases (56.2%) in the ≥ 60 years old group. Compared with the < 60 years old group, the ≥ 60 years old group showed a significant increase in the proportion of patients with active tumor-infiltrating lymphocytes ( P = 0.040), proportion of those with Ki-67 index ≥ 30% ( P = 0.010), and Charlson comorbidity index ( P = 0.002), but a significant decrease in the proportion of patients with BRAF/KIT/NRAS mutations ( P = 0.003), proportion of those receiving surgical treatment ( P = 0.034), and proportion of those receiving adjuvant therapy ( P = 0.042). There was a significant difference in the overall survival between the two groups (log-rank test, χ2 = 6.10, P = 0.014). The gender, metastasis status, presence or absence of ulceration, distant metastasis status, American Joint Committee on Cancer staging, Charlson comorbidity index, and Breslow thickness were important prognostic indicators affecting the overall survival in the elderly patients with melanoma. Multivariate Cox regression analysis showed that males ( P = 0.015, HR = 4.622, 95% CI: 1.352 - 15.798), presence of distant metastasis ( P = 0.013, HR = 9.844, 95% CI: 4.621 - 59.763), and Charlson comorbidity index ≥ 3 ( P = 0.038, HR = 3.149, 95% CI: 1.067 - 9.294) were independent risk factors affecting the overall survival in the elderly patients with melanoma. Conclusions:Compared with the non-elderly patients with melanoma, a higher Ki-67 index, a higher Charlson comorbidity index, less surgical treatment, and less adjuvant therapy were more common in the elderly patients with melanoma. Males, the presence of distant metastasis, and Charlson comorbidity index ≥ 3 appeared to be independent risk factors affecting the overall survival in the elderly patients with melanoma.

Objective:To analyze the values of platelet transforming growth factor-β (TGF-β) and SMAD family member 2 (Smad2) in patients′ peripheral platelets for CRC diagnosis and staging.Methods:Retrospective case-control study. Tumor tissues, paratumor tissues and peripheral blood samples were collected from 248 CRC patients (147 males, 101 females; age 21-93 years) diagnosed in the First Hospital of Jilin University from October 10th, 2020, to March 10th, 2025. Peripheral blood samples were also collected from 40 colorectal adenomatous polyp patients (21 males, 19 females; age 22-74 years) and 75 healthy individuals (43 males, 32 females; age 18-81 years) during the same period. Tissue homogenates and platelets were isolated using tissue disruption and gradient centrifugation, respectively. Total RNA was respectively extracted from tissues and platelets, and the expression levels of TGF-β and Smad2 were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) expressed as relative quantity 2 -ΔΔCt. Differences of TGF-β and Smad2 expression were compared between CRC tissues and adjacent tissues, as well as among CRC patients, polyp patients, and healthy controls. The relationship of platelet TGF-β and Smad2 expression with pathological features includingtumor stage, pathological type, and metastasis were analyzed. The efficiency of platelet TGF-β, Smad2, and their combination in diagnosing CRC was evaluated using receiver operating characteristic (ROC) curves. Results:The expression levels of TGF-β and Smad2 in CRC tumor tissues[1.09 (0.45, 2.00), 2.93 (0.78, 6.73)] were significantly higher than those in adjacent tissues[0.81 (0.27, 1.50), 1.29 (0.40, 2.63)] ( Z TGF-β=4.54, Z Smad2=6.67, both P<0.001). The expression levels of TGF-β and Smad2 in platelets of CRC patients[2.73(1.53, 4.38), 3.16 (1.58, 4.38)] were significantly higher than those in the colorectal polyp group[1.23(0.70, 2.54), 1.16(0.78, 2.27)] and the healthy control group[0.96(0.51, 1.88), 0.92 (0.55, 1.88)] ( H TGF-β=59.71, H Smad2=78.74, both P<0.001). Platelet TGF-β expression increased progressively with tumor stage (stage 1-4) ( P<0.05), while platelet Smad2 levels were higher in metastatic CRC compared with non-metastatic cases ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) for diagnosing CRC when combining platelet TGF-β and Smad2 was 0.81[95%Confidence interval( CI) 0.77—0.86], which was 0.90 (95% CI 0.86—0.93) if adding serum carcinoembryonic antigen (CEA). Conclusion:Platelet TGF-β and Smad2 expression correlates with the diagnosis and staging of CRC, demonstrating potential as liquid biopsy biomarkers for colorectal malignancies.