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.

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.

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.

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 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 compare the impact of manual right arm blood pressure measurement with computer-controlled blood pressure meter (CCBPM) on the detection rate of hypertension among elderly individuals.Method:This was a cross-sectional study. Elderly residents undergoing routine health check-up in a village in Jiangxi Province from April to June 2024 were enrolled. Manual blood pressure measurements were performed on the right arm using an electronic sphygmomanometer, while standardized dual-arm synchronized blood pressure assessments were conducted using the CCBPM. Blood pressure data were recorded from three sources: manual measurement on the right arm; the first CCBPM measurement on the arm with higher systolic blood pressure (CCBPM single); and the mean blood pressure of the arm with higher systolic blood pressure from two (if the difference between the first two measurements was less than 5 mmHg, 1 mmHg=0.133 kPa) or three (if the difference exceeded 5 mmHg) CCBPM measurements (CCBPM mean). Hypertension detection rates from these three datasets were compared. Subgroup analysis was performed according to age (60-74 years old as the elderly group,≥75 years old as the senior group) and gender. Intra-group correlation coefficient ( ICC) was analyzed to evaluate the consistency of blood pressure data of different blood pressure measurement methods, and Kappa value was analyzed to evaluate the consistency of hypertension classification determined by different blood pressure measurement methods. Results:A total of 1 498 participants were enrolled, aged (71.30±6.83) years old, including 678 males (45.26%). The blood pressure and heart rate measured by the artificial right arm blood pressure measurement were higher than those measured by CCBPM single (blood pressure: (140.09±17.19)/(82.40±10.93) mmHg vs. (135.31±18.98)/(81.23±10.51) mmHg; heart rate: (75.76±11.72) beats/min vs.(72.94±11.21) beats/min) and CCBPM mean (blood pressure: (140.09±17.19)/(82.40±10.93) mmHg vs. (134.64±18.39)/(80.28±9.78) mmHg; heart rate: (75.76±11.72) beats/min vs. (72.87±10.70) beats/min, all P<0.05). The detection rate of hypertension determined by CCBPM mean was significantly lower than that of artificial right arm (40.25% (603/1 498) vs.54.34% (814/1 498)) and CCBPM single (40.25% (603/1 498) vs. 44.79% (671/1 498), all P<0.05). Subgroup analysis showed that that the detection rate of hypertension determined by CCBPM mean was lower than that measured by artificial right arm regardless of gender and age (all P<0.05). The consistency of blood pressure data between artificial right arm and the CCBPM mean was moderate (systolic blood pressure: ICC=0.70; diastolic blood pressure: ICC=0.62), with less consistent classification ( Kappa=0.37). The consistency of blood pressure data between CCBPM single and CCBPM mean is extremely high (systolic blood pressure: ICC=0.94; diastolic blood pressure: ICC=0.91), with highly consistent classification ( Kappa=0.74). Conclusions:Artificial right arm blood pressure measurement in physical examinations may overestimate the hypertension detection rate, and the standardized dual-arm synchronized blood pressure measurement using CCBPM can reduce irregular blood pressure measurement.

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.