The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Human herpesvirus-6B (HHV-6B) reactivation is a significant contributor to nonrelapse mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective analysis describes three cases of HHV-6B reactivation following allo-HSCT, all of which achieved viral clearance with maribavir treatment following failure or intolerance to first-line antiviral therapy with foscarnet sodium. One patient diagnosed with HHV-6B encephalitis recovered without neurological sequelae. No adverse drug reactions to maribavir were observed. These findings provide preliminary evidence that maribavir may serve as an effective and safe salvage therapy for HHV-6B reactivation in patients receiving allo-HSCT.

Human herpesvirus-6B (HHV-6B) reactivation is a significant contributor to nonrelapse mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective analysis describes three cases of HHV-6B reactivation following allo-HSCT, all of which achieved viral clearance with maribavir treatment following failure or intolerance to first-line antiviral therapy with foscarnet sodium. One patient diagnosed with HHV-6B encephalitis recovered without neurological sequelae. No adverse drug reactions to maribavir were observed. These findings provide preliminary evidence that maribavir may serve as an effective and safe salvage therapy for HHV-6B reactivation in patients receiving allo-HSCT.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

Objective To evaluate the accuracy of selective laser melting of cobalt-chromium(CoCr)clasps with different build angles and support densities.Methods The 3D software constructed a sample clasp(reference object)with an undercut depth of 0.50 mm,which was then imported to a metal 3D printer to form CoCr clasps at different build angles(0°,45°,and 90°)and support densities(0.50,0.70,0.90,and 1.10 mm).A model scanner was used to obtain scans of all clasps(test objects);the test objects were aligned with the reference object and test subjects were aligned with each other through a best-fit alignment method using Geomagic software to obtain root mean square error(RMSE)values for the accuracy of the clasps.The data were statistically analyzed using one-way analysis of variance or non-parametric rank sum test(α=0.05).Results In terms of trueness,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For the different build angle groups with support densities of 0.70,0.90,and 1.10 mm,the RMSE values ranked as follows:45°group>90°group>0°group.In terms of precision,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For support density of 0.70 mm,the ranking was 90°group>45°group>0°group,while for support densities of 0.90 and 1.10 mm,the ranking was 45°group>90°group>0°group.Conclusion The accuracy of CoCr clasps varies with the build angle and support density.However,clasps produced at a build angle of 0°and a support density of 0.90 mm exhibit higher accuracy and are recommended for use in clinical and technical laboratories.

Objective To analyze the factors affecting the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B-associated cirrhosis(CHB-Cir)complicated by essential hypertension(EH)and explore the impact of EH on HCC risk in patients with CHB-Cir.Methods This study was conducted among the patients with CHB-Cir with or without EH received antiviral therapy in the Infectious Disease Department,Third Affiliated Hospital of Xinxiang Medical University from January,2017 to January,2024.The cases with insufficient follow-up time or missing data were excluded.The patients were subjected to propensity score matching in a 1:1 ratio to form an EH group and a non-EH group.The Kaplan-Meier method was used to compare the cumulative incidence of HCC between the two groups,and the Cox proportional hazards regression model was used to analyze the risk of HCC and the factors affecting HCC risk.Results A total of 390 CHB-Cir patients(274 male and 116 female patients)were enrolled in this study,including 195 with EH and 195 without EH.In these patients,EH was significantly correlated with the occurrence of HCC(HR=1.69,P=0.002).Multivariate analysis suggested that the male gender(HR=1.73,P=0.005),a family history of liver cancer(HR=2.23,P<0.001),elevated alpha-fetoprotein(HR=2.83,P=0.001),elevated glutathione reductase(HR=1.53,P=0.046),reduced high-density lipoprotein(HR=1.46,P=0.027),and elevated low-density lipoprotein(HR=2.29,P=0.003)were all significantly correlated with HCC occurrence,while elevated triglycerides(HR=0.37,P<0.001)was a protective factor against HCC.In the EH group,treatment with non-RASIs drugs(HR=2.77,P=0.021)and no treatment/diuretic treatment(HR=7.18,P<0.001)were significantly correlated with HCC occurrence.Conclusion Hypertension increases the risk of HCC in patients with CHB-Cir,suggesting the importance of controlling hypertension in these patients.

Objective To analyze the factors affecting the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B-associated cirrhosis(CHB-Cir)complicated by essential hypertension(EH)and explore the impact of EH on HCC risk in patients with CHB-Cir.Methods This study was conducted among the patients with CHB-Cir with or without EH received antiviral therapy in the Infectious Disease Department,Third Affiliated Hospital of Xinxiang Medical University from January,2017 to January,2024.The cases with insufficient follow-up time or missing data were excluded.The patients were subjected to propensity score matching in a 1:1 ratio to form an EH group and a non-EH group.The Kaplan-Meier method was used to compare the cumulative incidence of HCC between the two groups,and the Cox proportional hazards regression model was used to analyze the risk of HCC and the factors affecting HCC risk.Results A total of 390 CHB-Cir patients(274 male and 116 female patients)were enrolled in this study,including 195 with EH and 195 without EH.In these patients,EH was significantly correlated with the occurrence of HCC(HR=1.69,P=0.002).Multivariate analysis suggested that the male gender(HR=1.73,P=0.005),a family history of liver cancer(HR=2.23,P<0.001),elevated alpha-fetoprotein(HR=2.83,P=0.001),elevated glutathione reductase(HR=1.53,P=0.046),reduced high-density lipoprotein(HR=1.46,P=0.027),and elevated low-density lipoprotein(HR=2.29,P=0.003)were all significantly correlated with HCC occurrence,while elevated triglycerides(HR=0.37,P<0.001)was a protective factor against HCC.In the EH group,treatment with non-RASIs drugs(HR=2.77,P=0.021)and no treatment/diuretic treatment(HR=7.18,P<0.001)were significantly correlated with HCC occurrence.Conclusion Hypertension increases the risk of HCC in patients with CHB-Cir,suggesting the importance of controlling hypertension in these patients.

Objective To investigate the protective effect of adult human liver-derived stem cell exosomes (HLSC-exo) intravenously injected at different time points against acute liver injury induced by concanavalin A (ConA) in mice. Methods HLSC-exo was extracted by differential centrifugation. Western blot was used to measure the expression of the marker proteins CD9 and CD63, and nanoparticle tracking analysis was used to investigate particle size distribution. A total of 56 male C57BL/6 mice were randomly divided into blank control group, ConA model group, and HLSC-exo treatment group. The ConA model group and the HLSC-exo treatment group were further divided into 3-, 6-, and 12-hour subgroups according to the interval between phosphate buffer or HLSC-exo injection and ConA injection. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were measured, and the gross morphology and histopathology of the liver were compared between groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results HLSC-exo was a membranous vesicle with a diameter of 90-110 nm, with a clear saucer-like structure under an electron microscope and marked expression of its specific marker proteins CD9 and CD63. In the blank control group, the levels of ALT and AST were 31.81±6.74 U/L and 69.75±8.30 U/L, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had significant increases in the levels of ALT and AST (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had significant reductions in the levels of ALT and AST (225.58±115.59 U/L vs 1989.32±347.67 U/L, 1174.71±203.30 U/L vs 2208.33±349.96 U/L, 303.53±126.68 U/L vs 2534.27±644.72 U/L, 1340.70±262.56 U/L vs 2437.13±288.13 U/L, all P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had significantly greater reductions ( P < 0.001). In the blank group, the levels of IL-10 and TNF-α were 313.51±10.97 pg/ml and 476.05±7.31 pg/ml, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant reduction in the level of IL-10 (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant increase in the level of IL-10(331.61±10.46 pg/ml vs 266.20±8.15 pg/ml, 288.13±10.74 pg/ml vs 264.41±9.12 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater increase ( P < 0.001). Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant increase in the level of TNF-α (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the level of TNF-α (478.26±12.99 pg/ml vs 551.31±17.70 pg/ml, 515.58±7.18 pg/ml vs 556.21±11.15 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater reduction ( P < 0.001). Compared with the 3-and 6-hour ConA model groups in terms of the gross morphology and histopathology of the liver, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the degree of hepatocyte necrosis, and the 3-hour HLSC-exo treatment group had a basically complete lobular structure, with sporadic spotty necrosis; the 12-hour HLSC-exo treatment group had no significant improvement in hepatocyte necrosis compared with the 12-hour ConA model group. Conclusion Intravenous injection of adult HLSC-exo can alleviate acute liver injury induced by ConA in mice, and injection at 3 hours in advance has the most significant protective effect. Regulation of cytokines is one of the important mechanisms for HLSC-exo to alleviate liver injury.

Creating new germplasms and breeding new cultivars in peanut by radiation mutagenesis and tissue culture were conducted in this study, aiming to develop new breeding method of peanut. Mature seeds from Luhua 11, the most commonly grown peanut cultivar in Northern China, were treated by fast neutron irradiation. Then the embryo leaflets were separated from the irradiated seeds and inoculated on the media, and the regenerated seedlings were obtained through somatic embryogenesis pathway. The regenerated seedlings were grafted, acclimated and then transplanted into field and the selfed pods were harvested from 83 regenerated plants. The progenies were selected by the pedigree method, and 107 mutants were obtained from the progenies of the 83 regenerated plants. Different mutants showed obvious variation in many agronomic traits, including main stem height, branch number, pod shape and size, seed coat color, inner seed coat color, oil content and protein content etc. Yuhua 7, a new peanut variety with low oil content, early maturity and waterlogging tolerance was obtained. The yield of Yuhua 7 was over 14% higher than that of the mutagenic parent Luhua 11, and the oil content of kernels was 47.0%, lower than that of parent Luhua 11 with 52.1% oil content. Yuhua 7 had passed peanut variety regional multi-location trials in Liaoning Province in 2016 and its average yield was 13.8% higher than that of the control variety Baisha 1017. It had also passed national peanut variety registration, and the registration ID is "GPD peanut (2018) 370105". The results show that irradiation mutagenesis combined with tissue culture is an effective method for creating new germplasm and breeding new varieties of peanut.
Arachis ; Breeding ; China ; Fast Neutrons ; Plant Breeding ; Seeds