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 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.

Aluminum adjuvants (Alum), approved by the US Food and Drug Administration, have been extensively used in vaccines containing recombinant antigens, subunits of pathogens, or toxins for almost a century. While Alums typically elicit strong humoral immune responses, their ability to induce cellular and mucosal immunity is limited. As an alternative, layered double hydroxide (LDH), a widely used antacid, has emerged as a novel class of potent nano-aluminum adjuvants (NanoAlum), demonstrating advantageous physicochemical properties, biocompatibility and adjuvanticity in both humoral and cellular immune responses. In this review, we summarize and compare the advantages and disadvantages of Alum and NanoAlum in these properties and their performance as adjuvants. Moreover, we propose the key features for ideal adjuvants and demonstrate that LDH NanoAlum is a promising candidate by summarizing its current progress in immunotherapeutic cancer treatments. Finally, we conclude the review by offering our integrated perspectives about the remaining challenges and future directions for NanoAlum's application in preclinical/clinical settings.

Acute leukemia of ambiguous lineage (ALAL) is a rare type of acute leukemia and is extremely difficult to treat. Here, we present six patients with CD19-positive ALAL who were successfully treated with blinatumomab-based combination treatment in the front-line setting. Five were diagnosed with B-cell/myeloid mixed phenotype acute leukemia (MPAL) and one with B-cell/T cell MPAL. All six patients achieved complete remission after one cycle of blinatumomab combination treatment. Furthermore, 3 (50%) patients achieved MRD-negative (<0.01%) by flow cytometry and 2 (50%) of four patients with evaluable molecular MRD achieved molecular remission. At some point during the treatment, 5 (83.3%) patients achieved MRD negativity and all four patients with evaluable molecular MRD had molecular remission. The overall survival was 100%, and the event-free survival was 83.3% after a median follow-up time of 15 months. This study provides preliminary evidence that blinatumomab-based combination therapy is an effective and safe treatment for patients with CD19-positive ALAL in the front-line setting.

Acute leukemia of ambiguous lineage (ALAL) is a rare type of acute leukemia and is extremely difficult to treat. Here, we present six patients with CD19-positive ALAL who were successfully treated with blinatumomab-based combination treatment in the front-line setting. Five were diagnosed with B-cell/myeloid mixed phenotype acute leukemia (MPAL) and one with B-cell/T cell MPAL. All six patients achieved complete remission after one cycle of blinatumomab combination treatment. Furthermore, 3 (50%) patients achieved MRD-negative (<0.01%) by flow cytometry and 2 (50%) of four patients with evaluable molecular MRD achieved molecular remission. At some point during the treatment, 5 (83.3%) patients achieved MRD negativity and all four patients with evaluable molecular MRD had molecular remission. The overall survival was 100%, and the event-free survival was 83.3% after a median follow-up time of 15 months. This study provides preliminary evidence that blinatumomab-based combination therapy is an effective and safe treatment for patients with CD19-positive ALAL in the front-line setting.

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective:To investigate the therapeutic efficacy of venetoclax combined with avapritinib in treatment of refractory/relapsed acute myeloid leukemia (AML) with KIT gene mutation.Methods:The clinical data of 2 AML patients with KIT gene mutation who received venetoclax combined with avapritinib admitted to Canglang Hospital of Suzhou in October 2022 and November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Both patients with high-risk relapsed/refractory AML and KIT gene mutation were females; the one was 53 years and the other was 17 years. Case 1 was diagnosed with AML-M 2, and genetic testing revealed positive mutations in ASXL1, KIT, and RUNX1. The patient relapsed after transplantation and then was treated with venetoclax combined with avapritinib achieving morphologic leukemia-free status (MLFS). Case 2 was diagnosed with AML, and RUNX1-RUNX1T1 (AML1-ETO) fusion gene and KIT and DX15 gene mutations were detected. The patient was treated with venetoclax combined with avapritinib regimen after relapse, and the treatment regimen significantly reduced the tumor load. Complete remission was achieved after bridging to allogeneic hematopoietic stem cell transplantation. Conclusions:AML with KIT gene mutation is heterogeneous and some patients are difficult to treat with very poor prognosis. Bridging (secondary) hematopoietic stem cell transplantation can be the better treatment choice for relapsed patients achieving MLFS or complete remission after venetoclax combined with avapritinib treatment regimen.

Objective:To explore the relationship between parental rearing style and mental health of community correction offenders, as well as the mediating role of personality and coping styles in it.Methods:A questionnaire survey was conducted on 385 community correction offenders by the Egma Minnen av Bardndosna uppforstran(EMBU), symptom checklist-90 (SCL-90), NEO five-factor inventory(NEO-FFI) and simplified coping style questionnaire(SCSQ) from February to July 2022.SPSS 27.0 software was used for correlation analysis and regression analysis.AMOS 26.0 was used for the construction of structural equation, and Bootstrap was used for mediating effect analysis.Results:In parental rearing styles, the dimension of parents' severe punishment(19.09±5.32, 12.93±4.77), father's preference for subjects(9.29±3.30), father's excessive protection(10.40±2.19), mother's excessive interference and protection(33.81±6.06)and parents' refusal and denial (9.08±3.03, 12.17±4.25) were significantly positively correlated with the total score of SCL-90 (140.63±44.28)( r=0.114, 0.168, 0.121, 0.144, 0.224, 0.187, 0.220 respectively, all P<0.05). Parents' emotional warmth and understanding, parents' severe punishment and parents' refusal and denial were significantly correlated with coping styles ( r=0.420, 0.420, -0.189, -0.190, -0.174, -0.163 respectively, P<0.05). Neuroticism, extraversion, conformity, rigor in personality were significantly correlated with the total score of SCL-90 ( r=0.542, -0.442, -0.204, -0.202 respectively, P<0.05). Coping style was significantly negatively correlated with the total score of SCL-90 ( r=-0.352, P<0.05). The father's refusal and denial, the mother's emotional warmth and understanding, the mother's excessive interference and protection in the parental rearing styles could predict the mental health of community correction offenders ( β=0.191, -0.163, 0.233 respectively, P<0.05). Coping styles had a negative predictive effect on mental health ( β=-0.352, P<0.05). Neuroticism, preciseness and extra-version in personality could predict mental health ( β=0.461, 0.183, -0.281 respectively, P<0.05). The pathway coefficient of parental rearing styles → mental health was 0.261 ( P<0.001), and the direct effect was significant. The confidence intervals of parental rearing styles → personality traits → mental health path, parental rearing styles → coping tendency → mental health path did not include 0, indicating that partial mediating effect of personality traits and coping tendency were significant. Conclusion:Personality traits and coping styles play a mediating role in the influence of parental rearing style on mental health of community correction offenders.

Objective : To investigate the effects of dexmedetomidine on inflammatory factors and endoplasmic reticulum stress in myocardial ischemia reperfusion indu~ced brain injury. Methods : Twenty⁃four SPF⁃grade healthy male SD rats , weighing (200 220) g and aged (6 8) weeks , were divided into three groups (n = 8) by random number table method : sham operation group ( S group) myocardial ischemia reperfusion group ( IR group) and myocardial ischemia/reperfusion + Dex group (IR + Dex group) . After the rats were adapted to the feeding environment , the myocardial ischemia reperfusion injury model was established by ligating the anterior descending branch of the left coronary artery for 30 min and reperfusion for 120 min. At the beginning of reperfusion , IR + Dex group was given 25 μg/kg dexmedetomidine , S group and IR group were injected with equal volume normal saline. Rats were sacrificed by decapitation and brain tissue was taken and the changes of hippocampal cell structure of rats stained by HE were observed under light microscope. Serum inflammatory factors IL⁃6 , IL⁃8 and IL⁃10 were detected by ELISA. The expressions of Chop , Bip , p ⁃eif⁃2α and p ⁃perk in rat hippocampal tissues were determined by Western blot. Results : Compared with the S group , the IR group and the IR + Dex group showed aggravation of brain lesions , increased expression of inflammatory cytokines IL⁃6 and IL⁃8 (P < 0. 05) , and decreased expression of IL⁃10 ( P < 0. 05 ) . Hippocampal Chop , Bip , p ⁃eif⁃2α and p ⁃perk proteins were up⁃regulated ( P < 0. 05 ) . Compared with IR group , IR + Dex group showed reduced pathological injury , decreased expression of IL⁃6 and IL⁃8 (P < 0. 05) , increased expression of IL⁃10 (P < 0. 05) , and down⁃regulated expressions of Chop , Bip , p ⁃eif⁃2α and p ⁃perk in hippocampal tissues ( P < 0. 05 ) . Conclusion Dexmedetomidine preconditioning can reduce the brain injury caused by myocardial ischemia reperfusion , and its mechanism may be related to the inhibition of systemic inflammatory response and endoplasmic reticulum stress.

Objective:To evaluate the relationship between silence information regulator 1 (SIRT1) and signal transducers and activators of transcription 3 (STAT3) acetylation during high glucose-induced cardiac microvascular endothelial cell injury.Methods:Cardiac microvascular endothelial cells of Sprague-Dawley rats were cultured.The cells at the logarithmic growth phase were selected and divided into 3 groups ( n=24 each) using a random number table method: control group (C group), high glucose group (HG group) and high glucose+ SIRT1 agonist SRT1720 group (HG+ SRT group). The cardiac microvascular endothelial cells were seeded in a 6- or 96-well cell culture plate at a density of 2×10 5 cells/ml.When the cell density reached 50%, the culture medium was then replaced with high-glucose (glucose 33 mmol/L) DMEM culture medium containing with 10% fetal bovine serum and 1% double antibody in HG and HG+ SRT groups.In group HG+ SRT, 20 μmol/L SRT1720 was added simultaneously, and the cells were cultured at 37 ℃ in an incubator with 5% CO 2 for 24 h. The cell viability was determined by CCK-8 assay, the activity of superoxide dismutase (SOD) was detected using a spectrophotometer, the levels of lactic dehydrogenase (LDH), interleukin-6 (IL-6) and tumor necrosis factor-β (TNF-β) in the supernatant were detected by enzyme-linked immunosorbent assay, and the expression of SIRT1, acetylated STAT3 (ac-STAT3) and phosphorylated STAT3 (p-STAT3) was determined by Western blot. Results:Compared with C group, the cell viability and SOD activity were significantly decreased, levels of LDH, IL-6 and TNF-β in the supernatant were increased, expression of SIRT1 was down-regulated, and expression of ac-STAT3 and p-STAT3 was up-regulated in group HG and group HG+ SRT ( P<0.05). Compared with group HG, the cell viability and SOD activity were significantly increased, levels of LDH, IL-6 and TNF-β in the supernatant were decreased, expression of SIRT1 was up-regulated, and expression of ac-STAT3 and p-STAT3 was down-regulated in group HG+ SRT ( P<0.05). Conclusion:SIRT1 can alleviate high glucose-induced cardiac microvascular endothelial cell injury by promoting STAT3 deacetylation.