Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

Objective:To investigate the correlation between remnant cholesterol/high-density lipoprotein cholesterol ratio (RC/HDL-C) and metabolic dysfunction-associated fatty liver disease (MAFLD) in health check-up population.Methods:It was a cross-sectional study. A total of 5 299 subjects who received physical examination in the Health Management Center of Renmin Hospital of Wuhan University from January to December in 2023 and met the admission criteria were selected as the research subjects. The subjects were examined by demography, anthropometry, laboratory tests and liver instantaneous elastography. The Chi-square test, t-test, one-way analysis of variance, Mann-Whitney U test and Kruskal-Wallis H test were used to compare the indexes between the subjects with and without MAFLD. The subjects were divided into 4 groups (Q1-Q4 groups) according to the RC/HDL-C ratio quartiles by quartile method, and the indexes in each group were compared. The receiver operating characteristic (ROC) curves were drawn using MedCalc software and compared to assess the diagnostic efficacy of the RC/HDL-C ratio for MAFLD. Results:With the increase of RC/HDL-C ratio, the detection rate of MAFLD (12.56% vs 43.48%), male proportion (55.68% vs 85.60%), total cholesterol (TC) [(4.63±0.82) vs (5.10±1.06) mmol/L], triglyceride (TG) [0.90(0.71, 1.15) vs 2.58(1.96, 3.50) mmol/L], alanine aminotransferase (ALT) [17.00(13.00, 24.00) vs 26.00(19.00, 38.00) U/L], aspartate aminotransferase (AST) [20.00(17.00, 24.00) vs 23.00(19.00, 29.00) U/L], and controlled attenuation parameter (CAP) [(239.32±40.52) vs (274.60±44.98) dB/m] increased gradually, while high-density lipoprotein cholesterol (HDL-C) [1.40(1.20, 1.64) vs 0.93(0.84, 1.04) μmol/L] decreased gradually (all P<0.05). ROC curves showed that the AUC value of RC/HDL-C ratio was significantly higher in identifying MAFLD when compared with TC, HDL-C, LDL-C, non-HDL-C and RC (AUC=0.676, P<0.05). Conclusions:The RC/HDL-C ratio is positively correlated with the risk of morbidity of MAFLD in health check-up population.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To characterize the clinical and genetic features of 2 patients with interleukin-1 receptor associated kinase (IRAK) 4 deficiency and to assess the pathogenicity of their genetic variants.Methods:This case series included two patients diagnosed with IRAK4 gene deficiency at Shenzhen Children′s Hospital and the University of Hong Kong-Shenzhen Hospital between 2019 and 2024. Six healthy children without recent infections or immunodeficiency served as controls. Peripheral blood mononuclear cells were stimulated in vitro with Toll-like receptor 4 (TLR4) agonists, and cytokine levels were quantified using a protein chip assay.Results:The 2 patients, a 5-year-old boy and a 10-year-old girl, presented with recurrent invasive or non-invasive bacterial infections and impaired acute-phase inflammatory responses. Genetic testing identified a homozygous frameshift variant (c.540delT, p.F180Lfs*26) in Patient 1 and compound heterozygous frameshift variants (c.166delT, p.F56fs and c.629delG, p.R210fs) in Patient 2, all predicted to result in truncated IRAK4 proteins. Both patients received regular infection prophylaxis with favorable clinical outcomes. Controls consists of 3 males and 3 females, aged 5-17 years. Following TLR4 stimulation, cytokine levels in Patient 1, Patient 2, and controls (tumor necrosis factor-α 68.6, 103.0, 618.7 (392.7, 824.1); interleukin (IL)-1β 39.8, 10.8, 1 975.5 (1 556.0, 2 096.5); interferon-γ 8.6, 6.2, 13.5 (12.7, 14.9); granulocyte colony-stimulating factor 17.6, 15.9, 2 890.0 (1 622.0, 4 692.8); IL-6 140.1, 352.7, 7 222.5 (5 768.5, 8 043.5); and IL-17 47.5, 44.5, 59.7 (43.4, 69.5), respectively.Conclusions:IRAK4 deficiency should be suspected in patients with early-onset recurrent bacterial infections and attenuated inflammatory response. Homozygous and compound heterozygous frameshift variants in IRAK4 gene lead to truncated IRAK4 proteins and impared innate immune signaling.

Objective:To investigate the clinical significance of monitoring SIL::TAL1 fusion transcripts in the evaluation of treatment response and prognosis of children with T-acute lymphoblastic leukemia (T-ALL).Methods:A retrospective cohort study was conducted to analyze the clinical data of 46 newly diagnosed pediatric T-ALL with SIL::TAL1 fusion transcripts treated at Beijing Children′s Hospital Capital Medical University from November 2004 to December 2022. The SIL::TAL1 fusion transcripts were quantitatively detected at the initial diagnosis (TP0) and early stage of induction therapy (TP1), at the end of induction remission therapy (TP2), before consolidation therapy (TP3) and subsequent treatment. Patients were divided into negative and positive groups on SIL::TAL1 fusion transcripts level, differences of clinical features and survival among groups at TP0 to TP3 were analyzed. The χ2 test or Fisher exact test or Mann-Whitney U test was used to compare the clinical difference. Survival analysis was estimated by Kaplan-Meier method with Log-Rank testing. Multivariate analysis was conducted by Cox proportional hazards models. Results:Among the 46 children with SIL::TAL1 fusion transcripts, 36 were males and 10 were females, with the onset age of 6.8 (3.4, 9.5) years. The negative rates of SIL::TAL1 fusion transcripts for TP1,TP2, TP3, before delayed intensification Ⅰ treatment (TP4), before maintenance therapy (TP5) were 36% (13/36), 78% (32/41), 76% (32/42), 15/16, and 12/12, respectively. No significant difference was found on clinical features and prednisone response between groups at TP0-TP3 (all P>0.05). The 5-year events free survival (EFS) rate of patients classified as negative (32 cases) and positive (9 cases) groups at TP2 was (78±8)% and (33±16)%, respectively ( χ2=9.86, P=0.002), the 5-year overall survival (OS) rate was (81±7)% and (44±17)%, respectively ( χ2=6.40, P=0.011). The 5-year EFS rate of patients classified as negative (32 cases) and positive (10 cases) groups at TP3 was (78±8)% and (30±15)%, respectively ( χ2=13.04, P<0.001) and the 5-year OS rate was (84±6)% and (30±15)%, respectively ( χ2=15.95, P<0.001). Cox multivariate regression showed that positive of SIL::TAL1 transcript at TP3 was adverse independent prognostic factors for EFS and OS (EFS: HR=6.70, 95% CI 2.01-22.35, P=0.002; OS: HR=10.73, 95% CI 2.50-46.09, P=0.001). Conclusions:Monitoring SIL::TAL1 fusion transcripts can reflect the clinical treatment response. The level of SIL::TAL1 fusion transcripts at early period can predict long-term outcomes of these patients.

Objective To report the diagnosis,treatment,and verification process of a patient with sex development disorder whose chromosomal karyotype and genetic test results are inconsistent,and conduct a literature review to improve the understanding of the mosaic status of sexual development disorders.Methods A 14-year-old patient presented with primary amenorrhea on April 3,2020,at the First Affiliated Hospital of Hebei North University,exhibiting female sexual characteristics.The patient underwent ultrasonic/magnetic resonance imaging of gonads,assessment of gonadal axis function,chromosomal karyotype,and molecular genetic testing,as well as pelvic exploration,malignant gonads resection,and hormone replacement therapy,resulting in drug-induced menstruation.During the diagnosis and treatment,it was found that the patient's chromosomal karyotype analysis was inconsistent with the molecular genetic test results.Subsequently,samples from the three germ layer cells were taken,and fluorescence in situ hybridization(FISH)was used to detect the sex chromosomes in each germ layer cell.XY probes were used to label the gonadal pathological sections to explore the distribution differences of the Y chromosome in the gonads,and changes in anti-Müllerian hormone(AMH)levels before and after surgery were compared.Databases such as Wanfang and PubMed were searched to summarize relevant cohort study literature and understand the current status of research on this disease.Results The patient's body exhibited a significant differences between the 45,X and 46,XY cell lines in different germ layers and within the same layer tissues.The proportion of 45,X in buccal mucosal cells derived from the ectoderm was 30%(6/20),in peripheral blood lymphocytes derived from the mesoderm was 9.7%(11/114),and in bladder shed cells derived from endoderm was 20.4%(22/108).The gonadal pathological sections labeled with XY probes indicated a mosaic state with a reduced Y-chromosome;where the epididymal structure area had a 45,X cell line mosaic of 50.0%,and the malignant area had a normal"Y"content.After gonadal resection,AMH levels significantly dropped from 7.28 pmol/L to＜0.07 pmol/L.Literature review revealed that patients with 45,X/46,XY have a complex phenotype spectrum,most with features of Turner syndrome,and female phenotypes are at risk of gonadal tumors.Conclusions In the diagnosis of difficult cases of sex development disorders,when performing peripheral blood karyotype testing,the number of counted cells and analyzed cells should be increased as much as possible,and multi-germ layer cell sampling should be performed.Gonads with a high"Y"mosaic rate are more prone to malignancy in the abdominal cavity.Detecting AMH levels can distinguish cryptorchidism and anorchidism in sexual development disorders with Y chromosomes.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Objective:To explore the impact of marital status on the prognosis of adult patients with primary intrahepatic cholangiocarcinoma.Methods:3283 patients with primary intrahepatic single tube carcinoma from 1998 to 2018 were collected.They were divided into married group(n=1999)and unmarried group(n=1284)based on marital status.The clinical data of adult patients with primary intrahepatic cholangiocarcinoma of different marital statuses were compared.Kaplan Meier survival curves were used to analyze the survival status of adult patients with primary intrahepatic cholangiocarcinoma in different marital statuses.Univariate and multivariate Cox regression analysis were used to investigate the factors affecting the survival of adult patients with primary intrahepatic cholangiocarcinoma.Kaplan Meier survival curves were used to analyze the survival status of adult patients with primary intrahepatic cholangiocarcinoma in different marital statuses,including whether they received surgical treatment,radiotherapy treatment,and gender differences.Results:The proportion of male patients,the proportion of white patients,the proportion of patients over 60 years old,the proportion of patients receiving surgical treatment,the proportion of patients receiving radiotherapy,and the proportion of patients receiving chemotherapy in the married group were higher than those in the unmarried group(P＜0.05).Kaplan Meier survival curve analysis results showed that,the 3-month and 5-year survival rates between married and unmarried groups were Log-rank test P＜0.05.Multivariate Cox regression analysis showed that,age over 60 years old,later tumor stage,surgical treatment,radiotherapy,and chemotherapy were risk factors for survival in adult patients with primary intrahepatic cholangiocarcinoma(P＜0.05).Kalplan Meier survival curve results showed that,there was no significant difference in 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who received surgical treatment(Log-Rank test P=0.381).There was a significant difference in the 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who have not received surgical treatment(Log-Rank test P=0.015).There was no significant difference in 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who received radiotherapy(Log-Rank test P=0.073).There was a significant difference in the 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who have not received radiotherapy(Log-Rank test P＜0.001).There was no significant difference in 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who received chemotherapy(Log-Rank test P=0.337).There was a significant difference in the 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who have not received chemotherapy(Log-Rank test P＜0.001).There was no significant difference in the survival status of male patients with primary intrahepatic cholangiocarcinoma in adults of different marital statuses(Log-Rank test P=0.136).There were differences in the survival status of female patients with primary intrahepatic cholangiocarcinoma in adults of different marital statuses(Log-Rank test P＜0.001).Conclusion:Male,white,and over 60 years old are risk factors for the occurrence of primary intrahepatic cholangiocarcinoma in adults.Among them,more than half of the patients did not receive surgery or radiotherapy treatment,and about half of the patients did not receive chemotherapy.Married individuals are more likely than unmarried individuals to undergo anti-tumor treatments such as surgery,radiotherapy and chemotherapy.The staging of intrahepatic cholangiocarcinoma and whether surgery or chemotherapy is received are independent predictors of long-term survival.Marital status is not an independent predictor and can indirectly affect long-term survival.Male marital status has no significant survival benefits for this disease,while female marital status has survival benefits for this disease.The marital status of patients with intrahepatic cholangiocarcinoma who have not undergone radiotherapy,chemotherapy,or surgical intervention has a significant impact on their survival outcomes.

Diabetic encephalopathy(DE)is a complication of the central nervous system induced by diabetes,characterized by insidious onset and complex pathological mechanisms.Recent research has revealed that the pathological mechanisms of DE are closely associated with the imbalance of intercellular communica-tion across multiple organs.Exosomes,serving as vital media-tors of intercellular communication,are involved in the patholog-ical progression of DE and hold promise as diagnostic biomarkers and therapeutic targets for DE.Traditional Chinese medicine(TCM)can improve communication between brain cells and be-tween peripheral and brain tissues by regulating exosomes and their contents,thereby preventing and treating DE.Meanwhile,exosomes,as targeted delivery carriers of active molecules,can carry TCM monomers more easily across the blood-brain barrier to prevent and treat DE.In light of this,this review summarizes the regulatory role of exosomes in the pathological progression of DE and explores the enormous potential of TCM in the preven-tion and treatment of DE by regulating exosomes and using exo-somes as traditional Chinese medicine carriers,aiming to pro-vide new evidence for the prevention and treatment of DE with TCM.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.