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.

BACKGROUND:Vertigo is closely related to clinical neurological disorders.When neurons are damaged or dead,it may lead to abnormalities in the vestibular system and trigger vertigo symptoms.Therefore,it is necessary to explore and analyze the hotspots related to vertigo that are common in clinical neurology. OBJECTIVE:To analyze the vertigo-related histopathological changes in clinical neurology and the research hotspots worldwide using bibliometric methods. METHODS:The WanFang database and Web of Science core set database were searched by the first author to retrieve the research-related literature published from 2014-2023 on the treatment of common vertigo in clinical neurology.A bibliometric analysis of the number of publications,country/region,institution,keywords,co-cited literature,and highly cited literature was peformed using VOSviewer_1.6.19 software to summarize the research hotspots in this research field. RESULTS AND CONCLUSION:Web of Science core set database had the highest number of 174 publications in this field in 2022,and WanFang database had the highest number of 133 publications in this field in 2020.The top 3 countries with the highest number of publications are the United States,Germany,and China.The University of Munich,Germany is the international institution with the highest number of publications in this field,while Chengdu University of Traditional Chinese Medicine is the Chinese institution with the highest number of publications in this field.The results of keyword analysis showed that the research hotspot diseases in this field in China are mainly Meniere's disease,cervical vertigo,senile vertigo,benign paroxysmal positional vertigo,isolated vertigo,and hypertensive vertigo,and the treatments include acupuncture,rehabilitation,medication(gastrodin,Banxia Baizhu Tianma Tang),and manipulative reduction.International research hotspot diseases in this field mainly include benign paroxysmal positional vertigo,vestibular disorders in new coronavirus cases,Meniere's disease,vestibular schwannoma,acoustic neuromas,and vestibular migraines,etc.,and the hotspot treatments are antivertiginous medications,antidepressant and anxiolytic treatments,and microsurgery.The results of literature co-citation analysis showed that for acute vestibular syndrome with persistent vertigo as the main symptom,three-step bedside ophthalmoscopy(HINTS:Head-Impact-Nystagmus-Strabismus Test)is more sensitive than early MRI in the diagnosis of combined strokes in patients with acute vestibular syndrome,which is the most peer-recognized method of detecting strokes in vestibular syndrome,whereas hormonal therapy is more effective to treat vestibular neuritis patients with paroxysmal vertigo as the main symptom.The results of highly cited literature analysis showed that,in the hot literature included in WanFang database in the past 10 years,acupuncture at Fengchi point and the acupuncture method of inducing resuscitation to improve posterior circulation ischemic vertigo have achieved certain results.The literature published in the past 3 years has indicated that Ginkgo biloba leaf extract+gastrodin,acupuncture+Banxia Baizhu Tang,betahistine+gastrodin,vestibular rehabilitation training+Epley Maneuver,all can improve the vertigo symptoms to different degrees.While there were no featured anti-vertigo drugs indicated in the literature in the Web of Science core set data in the recent 10 years,and most of them are based on traditional anti-vertigo drugs and microsurgery.However,there are a few case reports in the international literature in the last 3 years that found that COVID-19 infection may lead to vestibular neuritis and vertigo symptoms.The onset and progression of vertigo may be closely related to neuronal damage and regeneration.For example,viral infections,inflammatory stimuli,or other pathologic factors may lead to neuronal damage or death,thereby affecting the function of the vestibular system.Vertigo-related diagnosis and treatment standardization guidelines have been published both domestically and internationally.Currently,international guidelines recommend the combination of vestibular rehabilitation and physical rehabilitation for the treatment of vertigo,and Chinese guidelines recommend the combination of Chinese and Western medicine,reduction and acupuncture.However,the level of evidence is not very high,so a large number of large-sample,multicenter randomized controlled trials on anti-vertigo treatment are needed in the future.

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.

Objective:This study aimed to analyze cytomegalovirus (CMV) reactivation and its influencing factors in patients with B-lymphocyte malignancy who received chimeric antigen receptor T (CAR-T) cell therapy.Methods:This study retrospectively reviewed patients with B-lymphocyte malignancy who received CAR-T cell therapy in the First Affiliated Hospital of Soochow University from January 2021 to December 2023. The data of patients who underwent CMV-DNA detection and/or pathogen metagenomic sequencing twice or more within 100 days after CAR-T cell therapy were analyzed. The clinical characteristics of the CMV reactivation and non-activation groups were compared. The factors related to CMV reactivation were analyzed with the Chi-square test and nonparametric rank sum test, and the risk factors were examined with Logistic regression.Results:This study included 86 patients, among whom 18 (20.9%) had CMV reactivation, and the median time of reactivation was 20 (1-95) days. All of the 18 patients had CMV viremia, and no CMV disease was observed. Seven patients turned to the latent state after continuing acyclovir antiviral therapy, and 11 patients returned to the latent state after upgrading the antiviral therapy to first-line drugs, including ganciclovir and foscarnet sodium. Six or more courses of anti-tumor treatment before CAR-T cell therapy, allogeneic hematopoietic stem cell transplantation within 2 years before CAR-T cell therapy, non-remission before treatment, and the use of high-dose glucocorticoids and/or tocilizumab were related to CMV reactivation, among which allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and the use of high-dose glucocorticoids and/or tocilizumab treatment were independent risk factors for CMV reactivation.Conclusion:Patients with B-lymphocyte malignancy who received CAR-T cell therapy have the risk of CMV reactivation, especially for those who received allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and those who received high-dose glucocorticoids and/or tocilizumab treatment.

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.

Objective:This study aimed to analyze cytomegalovirus (CMV) reactivation and its influencing factors in patients with B-lymphocyte malignancy who received chimeric antigen receptor T (CAR-T) cell therapy.Methods:This study retrospectively reviewed patients with B-lymphocyte malignancy who received CAR-T cell therapy in the First Affiliated Hospital of Soochow University from January 2021 to December 2023. The data of patients who underwent CMV-DNA detection and/or pathogen metagenomic sequencing twice or more within 100 days after CAR-T cell therapy were analyzed. The clinical characteristics of the CMV reactivation and non-activation groups were compared. The factors related to CMV reactivation were analyzed with the Chi-square test and nonparametric rank sum test, and the risk factors were examined with Logistic regression.Results:This study included 86 patients, among whom 18 (20.9%) had CMV reactivation, and the median time of reactivation was 20 (1-95) days. All of the 18 patients had CMV viremia, and no CMV disease was observed. Seven patients turned to the latent state after continuing acyclovir antiviral therapy, and 11 patients returned to the latent state after upgrading the antiviral therapy to first-line drugs, including ganciclovir and foscarnet sodium. Six or more courses of anti-tumor treatment before CAR-T cell therapy, allogeneic hematopoietic stem cell transplantation within 2 years before CAR-T cell therapy, non-remission before treatment, and the use of high-dose glucocorticoids and/or tocilizumab were related to CMV reactivation, among which allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and the use of high-dose glucocorticoids and/or tocilizumab treatment were independent risk factors for CMV reactivation.Conclusion:Patients with B-lymphocyte malignancy who received CAR-T cell therapy have the risk of CMV reactivation, especially for those who received allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and those who received high-dose glucocorticoids and/or tocilizumab treatment.

Objective:To compare the medium-term clinical effects of arthroscopic double row repair between traumatic and degenerative medium supraspinatus tear.Methods:A retrospective study was conducted to analyze the clinical data of 23 patients who had been treated for traumatic or degenerative medium supraspinatus tear by the same arthroscopic double row repair and postoperative rehabilitation at Sports Medicine Center, The First Hospital Affiliated to Army Medical University between January 2015 and August 2020. They were assigned into 2 groups according to different tears. In the traumatic group of 8 cases of traumatic medium supraspinatus tear, there were 5 males and 3 females with an age of (46.1±4.3) years and a tear size of (1.3±1.0) cm 2. In the degenerative group of 15 cases of degenerative medium supraspinatus tear, there were 4 males and 11 females with an age of (59.9±8.1) years and a tear size of (4.1±1.1) cm 2. At preoperation and the last follow-up, the shoulder pain was evaluated by visual analogue scale (VAS), and the shoulder function by American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score and Simple Shoulder Test (SST); the improvements in active range of motion (ROM) of the shoulder were recorded at the last follow-up. Results:The 2 groups were comparable because there was no significant difference between them in the general clinical data ( P>0.05). The traumatic and degenerative groups were followed up for (40.3±11.2) and (36.4±12.4) months, respectively. At the last follow-up, the improvements in range of anterior flexion and internal rotation vertebral rank in the degenerative group [55.3°±33.6° and (4.1±1.3) ranks] were significantly greater than those in the traumatic group [27.5°±22.5° and (2.3±1.9) ranks] ( P<0.05). At the last follow-up, the VAS, ASES, Constant-Murley, and SST scores in the degenerative group were improved respectively by (3.7±0.8), (40.9±14.0), (38.4±9.4), and (6.5±1.4) points compared with their preoperative values, significantly greater than those in the traumatic group [(2.3±0.7), (19.6±14.6), (19.2±7.9), and (3.8±0.7) points] ( P<0.05). Conclusion:Arthroscopic double row repair can achieve significant medium-term improvements in shoulder function for both traumatic and degenerative medium supraspinatus tears, but the improvements may be grater for the degenerative ones.

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.