Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

BACKGROUND:At present,the incidence of scoliosis is increasing year by year,especially in adolescent idiopathic scoliosis.Therefore,it is more and more important to strengthen the research on the treatment of adolescent scoliosis. OBJECTIVE:To summarize the current status,hotspots,emerging trends,and frontiers of global research on the treatment of adolescent idiopathic scoliosis to provide reference and guidance for future related research. METHODS:The literature related to the treatment of adolescent idiopathic scoliosis was retrieved on the Web of Science Core Collection(WOSCC)database from 2013 to 2023.CiteSpace 6.2.R1 software was used for visual analysis of countries,institutions,authors,and keywords. RESULTS AND CONCLUSION:(1)A total of 561 English articles were included in this study.Among countries,institutions,and authors,the United States has contributed the most.Nanjing University and Qiu,Yong(Affiliated Drum Tower Hospital,Nanjing University School of Medicine)are the most published institution and author.The academic journal with the largest number of articles is the European Spine Journal.(2)In the analysis of cited literature,the top 10 most cited articles mainly describe the effects of surgical treatment and conservative treatment on improving adolescent idiopathic scoliosis,especially improving the curvature of patients.(3)Through the summary of highly cited articles and the keyword clustering,keyword prominence in-depth mining,the research hotspots are currently the relationship between Cobb angle and treatment choice,the therapeutic effect of exercise therapy and the therapeutic effect of posterior vertebral fusion.(4)The prognosis of patients with different curvatures has not been studied in depth,and the etiology of adolescent idiopathic scoliosis has not been clarified,so the relationship between curvature and prognosis and the etiology of adolescent idiopathic scoliosis may be a new research trend in the future.

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

BACKGROUND: The correlation between geriatric nutritional risk index (GNRI) and the prognosis of patients with osteoporosis or osteopenia has not been studied. This study aims to explore the relationship between GNRI and the cardiovascular disease (CVD) and all-cause mortality rates in elderly patients with osteoporosis or osteopenia. METHODS: This study included 4756 patients with osteoporosis and osteopenia from five cycles of the National Health and Nutrition Examination Survey (NHANES). We used multivariable Cox regression and subgroup analyses to investigate the correlation between GNRI and mortality rates. The restricted cubic spline analysis was used to assess the dose-response relationship between GNRI and mortality risk. Mediation analysis was conducted to examine the mediating effect of chronic kidney disease on the relationship between nutritional risk and mortality. RESULTS: During a median follow-up period of 114 months, a total of 1241 deaths (26.09%) occurred, including 300 deaths due to CVD (6.31%). In the fully adjusted Model 3, compared to the no-risk group, the risk group showed significantly increased all-cause mortality risk (HR = 2.05, 95% CI: 1.74-2.40) and CVD mortality risk (HR = 1.88, 95% CI: 1.30-2.71). The restricted cubic spline analysis indicated a non-linear association between GNRI and all-cause mortality risk as well as CVD mortality risk. The mediation analysis results indicated that chronic kidney disease mediates 16.9% of the effect of nutritional risk on all-cause mortality and 25.3% on CVD mortality risk. CONCLUSIONS GNRI can serve as a predictive factor for all-cause and CVD mortality rates in elderly patients with osteoporosis or osteopenia.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].