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

Cell death is divided into uncontrolled accidental cell death (ACD) and controllable regulatory cell death (RCD). RCD is also known as programmed cell death (PCD) under physiological conditions. PANoptosis is a recently discovered inflammatory RCD pathway regulated by a cytoplasmic polymeric protein complex called PANoptosome. This complex has the key features of apoptosis, pyrodeath, and/or necrotic apoptosis, but cannot be explained by any of these 3 RCD pathways alone. However, the specific role of PANoptosis in human tumor cells remains to be clarified. At present, the understanding of the molecular mechanism of PANoptosis and the assembly of PANoptosome is very limited, but several important regulatory targets have been identified such as melanoma deficiency factor 2 (AIM2), caspase family members(including CASP3, CASP6, and CASP8), Z-DNA-binding protein 1 (ZBP1), receptor-interacting protein kinase 1/3 (RIPK1/3) and interferon regulatory factor 1 (IRF1). The discovery of these markers indicates a breakthrough for the optimization of cancer treatment strategies.

[Objective]To explore the outcomes and surgical experiences of 267 cases of extracardiac conduit total cavopulmonary connection(TCPC)in patients with functional single ventricles.[Methods]Clinical data were collected from 267 patients who underwent extracardiac conduit TCPC at Guangdong Provincial People's Hospital from October 2004 to August 2021.Among them,185 were male(69.3%)and 82 were female(30.7%).The age was 5.71(4.08-10.90)year,and the weight was 17.5(14.5-26.2)kg.A median sternotomy approach was used,and the surgery was completed under cardiopulmonary bypass.The preoperative,intraoperative and postoperative follow-up data of the patients were collected,and the survival prognosis and its influencing factors were analyzed.[Results]The operative time was 330.0(267.5-405.0)min,the cardiopulmonary bypass time was 124.0(96.0-163.0)min,and the aortic cross-clamp time was 48.0(0.0-81.0)min.The duration of mechanical ventilation after surgery was 8.7(5.0-19.1)h,and the hospital stay was 34.0(28.0-49.0)d.The follow-up period was 8.0(4.6-11.0)year,with 8 early deaths(3.0%),20 late deaths(7.5%).The independent risk factors of fatality in patients after extracardiac conduit TCPC included male,heterotaxy syndrome,preoperative pulmonary artery pressure,intraoperative blood loss,the duration of mechanical ventilation,and the 48 h average vasoactive-inotropic score.[Conclusions]The extracardiac conduit TCPC is quite effective in treating patients with functional single ventricle.The early postoperative fatality is low,while the late fatality is relatively high.Therefore,it is necessary to pay close attention to the long-term survival situation of this group of patients.The analysis of risk factors emphasizes the importance of perioperative refined assessment and individualized treatment.It may help further improve the therapeutic outcomes of such surgeries,including selecting appropriate patients,performing careful operations,ensuring meticulous hemostasis,and shortening the duration of postoperative mechanical ventilation.

Cell death is divided into uncontrolled accidental cell death (ACD) and controllable regulatory cell death (RCD). RCD is also known as programmed cell death (PCD) under physiological conditions. PANoptosis is a recently discovered inflammatory RCD pathway regulated by a cytoplasmic polymeric protein complex called PANoptosome. This complex has the key features of apoptosis, pyrodeath, and/or necrotic apoptosis, but cannot be explained by any of these 3 RCD pathways alone. However, the specific role of PANoptosis in human tumor cells remains to be clarified. At present, the understanding of the molecular mechanism of PANoptosis and the assembly of PANoptosome is very limited, but several important regulatory targets have been identified such as melanoma deficiency factor 2 (AIM2), caspase family members(including CASP3, CASP6, and CASP8), Z-DNA-binding protein 1 (ZBP1), receptor-interacting protein kinase 1/3 (RIPK1/3) and interferon regulatory factor 1 (IRF1). The discovery of these markers indicates a breakthrough for the optimization of cancer treatment strategies.

AIM: To detect the expression levels of long non-coding RNA(lncRNA)X-inactive specific transcript(XIST)and silencing information regulatory factor 2 associated enzyme 1(SIRT1)in serum of patients with type 2 diabetes mellitus(T2DM), and to explore their correlation with diabetic retinopathy(DR)and their diagnostic value. METHODS: Prospective study. A total of 214 patients with T2DM admitted to our hospital from January 2022 to February 2023 were selected as the research subjects. Based on whether retinopathy occurred, they were divided into 126 cases(126 eyes)in the non-DR group and 88 cases(88 eyes)in the DR group. An additional 130 healthy individuals who underwent a physical examination during the same period were selected as the control group. The serum levels of lncRNA XIST and SIRT1 in the three groups were measured and compared. The relationship between lncRNA XIST and SIRT1 expression with DR was analyzed using Pearson's method. The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum lncRNA XIST, SIRT1, and their combination for DR. Multivariate Logistic regression analysis was performed to investigate the factors affecting the occurrence of DR in T2DM patients.RESULTS: Compared with the control group, the levels of serum lncRNA XIST and SIRT1 in the non-DR group and DR group were successively decreased(all P<0.05). The levels of serum lncRNA XIST and SIRT1 were positively correlated in DR patients(r=0.639, P<0.05). ROC analysis showed that the area under the curve(AUC)for predicting DR by combining serum lncRNA XIST and SIRT1 was 0.940, which was higher than the AUC by serum lncRNA XIST and SIRT1 alone(0.855, 0.875). Logistic regression analysis showed that lncRNA XIST(OR=0.752)and SIRT1(OR=0.694)were influencing factors for the occurrence of DR(both P<0.01).CONCLUSION: The serum levels of lncRNA XIST and SIRT1 are both lower in DR patients, and the combination of lncRNA XIST and SIRT1 has a better assessment capacity for the occurrence of DR.

Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

A 64-year-old woman was treated with Sindillizumab immunotherapy for classic Hodgkin lymphoma.After 7 cycles,the patient developed fever,fatigue,poor appetite,and other symptoms.Auxiliary examination after admission showed that hemoglobin,platelets,white blood cells,and fibrinogen decreased,liver enzymes increased,serum ferritin increased significantly(3 727.56 μg·L-1),and spleen enlargement,which was finally considered to be sindilizumab associated hemophagic cell syndrome.The patient was given methylprednisolone sodium succinate 60 mg·d-1 intravenously for 2 days,40 mg·d-1 intravenously for 4 days,and 30 mg·d-1 intravenously for 1 day,and their symptoms improved significantly,and the temperature,blood count,aminotransferase and other indicators gradually returned to normal.After discharge,she was changed to prednisone 30 mg·d-1 oral therapy,and the dose was reduced by 10 mg per week until withdrawal.The patient did not restart sindilizumab after discharge,and the serum ferritin gradually returned to normal level during follow-up,and no hemophagocytic syndrome-related symptoms appeared again.It was suggested that during the use of immune checkpoint inhibitors,patients with unexplained fever and decreased blood counts,in the absence of improvement in anti-infection,the possibility of hemophagocytic syndrome should be considered and relevant diagnostic tests such as serum ferritin should be improved as soon as possible,and glucocorticoid therapy should be turned on to avoid delay of the disease.

Objective:To evaluate the effect of activation of splenic plasmacytoid dendritic cells (pDCs) on myocardial ischemia-reperfusion (I/R) injury in mice.Methods:The experiment was performed in two parts. Animal experiment Thirty-six SPF healthy male C57BL/6J mice, aged 10 weeks, weighing 22-27 g, were assigned to 3 groups ( n=12 each) using a random number table method: sham operation group (Sham group), myocardial ischemia group (MI group) and myocardial I/R group (MI/R group). The myocardial ischemia was induced by occluding the left anterior descending coronary artery for 40 min in MI group, while the model of myocardial I/R was established by occlusion of the left anterior descending coronary artery for 40 min followed by 1-h reperfusion in MI/R group. Following successful preparation of the model, 3 animals from each group were randomly selected, and their hearts were removed for determination of myocardial infarct size through a combination of TTC and methylene blue double staining. Another 3 animals from each group were randomly selected, and their hearts were removed for examination of pathological changes of myocardial tissues using HE staining. Blood samples were collected from the abdominal aorta of 6 mice left in each group for determination of plasma interferon alpha (IFN-α) concentrations by enzyme-linked immunosorbent assay. Then the animals were sacrificed and hearts were harvested for collection of cardiac perfusate (CP). Cell experiment Twelve SPF healthy male C57BL/6J mice, aged 10 weeks, weighing 22-27 g, were selected and the splenic pDCs were isolated using anti-mPDCA-1 MicroBeads according to the manufacturer′s instructions (with a positivity rate of >85% for the isolated cells). The cells were divided into 4 groups: group pDCs stimulated by CP in Sham group (pDCs+ CP-Sham group), group pDCs stimulated by CP in MI group (pDCs+ CP-MI group), group pDCs stimulated by CP in MI/R group (pDCs+ CP-MI/R group) and pDCs stimulated by PBS group (pDCs+ PBS group). The CP in Sham, MI and MI/R groups and PBS were used to induce and culture pDCs for 8 h. Flow cytometry was employed to detect the expression of CD45 and co-stimulatory molecules CD80, CD86 and Major Histocompatibility Complex Ⅱ (MHC Ⅱ) on the surface of pDCs. The levels of IFN-α in the cell culture supernatant were determined using enzyme-linked immunosorbent assay. Results:Animal experiments Compared with Sham group and MI group, the percentage of myocardial infarct size was significantly increased, the concentrations of plasma IFN-α were increased ( P<0.05), and cardiomyocytes displayed evident vacuolar degeneration, severe myocardial fiber rupture, and infiltration of a substantial number of inflammatory cells in MI/R group. There was no significant difference in each parameter between Sham group and MI group ( P>0.05). Cell experiment Compared with pDCs+ CP-Sham group, the expression of CD80, CD86 and MHCⅡ was significantly up-regulated in pDCs+ CP-MI group ( P<0.05), and no significant change was found in the aforementioned parameters in pDCs+ CP-MI/R group ( P>0.05). The expression of aforementioned parameters was significantly up-regulated in pDCs+ CP-MI group as compared with pDCs+ CP-MI/R group ( P<0.05). Compared with pDCs+ CP-Sham group and pDCs+ CP-MI/R group, the concentrations of IFN-α in the cell culture supernatant were significantly increased in pDCs+ CP-MI group ( P<0.05). There was no statistically significant difference in the concentrations of IFN-α between pDCs+ CP-MI/R group and pDCs+ CP-Sham group ( P>0.05). Conclusions:The mechanism underlying myocardial I/R injury may be related to activation of splenic pDCs leading to the production of IFN-α following myocardial ischemia in mice.

Objective:To investigate the differences in the incidence of QT interval prolongation between moxifloxacin and levofloxacin in anti-infective therapy among cardiology intensive care unit (CCU) patients, and to analyze the risk factors for QT interval prolongation.Methods:The data of patients who received anti-infective treatments with moxifloxacin and levofloxacin in CCU of Xiaogan Central Hospital from January 2020 to December 2022 were collected and analyzed retrospectively. The clinical characteristics in the 2 groups were compared. Potential influencing factors of QT interval prolongation were analyzed using univariate regression analysis. Variables with P<0.2 were included in a logistic regression model for multivariate analysis. The effect values were expressed as odds ratio ( OR) and its 95% confidence interval ( CI). Results:A total of 146 patients were included in the study, with 76 patients in the moxifloxacin group and 70 patients in the levofloxacin group. In the moxifloxacin group, 18 out of 76 patients (23.68%) experienced QT interval prolongation, while in the levofloxacin group, 6 out of 70 patients (8.57%) experienced QT interval prolongation; the difference between the 2 groups was statistically significant ( P=0.025). There were no statistically significant differences in other factors between the 2 groups. Univariate regression analysis showed that female ( OR=2.958, 95% CI: 1.144-7.647, P=0.025), myocardial infarction ( OR=2.958, 95% CI: 1.144-7.647, P=0.025), concomitant use of amiodarone ( OR=2.569, 95% CI: 1.042-6.337, P=0.040) and escitalopram were influencing factors of QT interval prolongation. Factors with P<0.2 were entered in the multivariate logistic regression analysis, and the results showed that female ( OR=3.616, 95% CI: 1.240-10.538, P=0.019), hypokalemia ( OR=2.953, 95% CI: 1.263-6.905, P=0.012), and myocardial infarction ( OR=3.026, 95% CI: 1.057-8.666, P=0.039) were independent risk factors for QT interval prolongation. Conclusions:Moxifloxacin is associated with a higher incidence of QT interval prolongation compared to levofloxacin. Female and patients with hypokalemia and myocardial infarction have high risks for QT interval prolongation.

Objective:To investigate the differences in the incidence of QT interval prolongation between moxifloxacin and levofloxacin in anti-infective therapy among cardiology intensive care unit (CCU) patients, and to analyze the risk factors for QT interval prolongation.Methods:The data of patients who received anti-infective treatments with moxifloxacin and levofloxacin in CCU of Xiaogan Central Hospital from January 2020 to December 2022 were collected and analyzed retrospectively. The clinical characteristics in the 2 groups were compared. Potential influencing factors of QT interval prolongation were analyzed using univariate regression analysis. Variables with P<0.2 were included in a logistic regression model for multivariate analysis. The effect values were expressed as odds ratio ( OR) and its 95% confidence interval ( CI). Results:A total of 146 patients were included in the study, with 76 patients in the moxifloxacin group and 70 patients in the levofloxacin group. In the moxifloxacin group, 18 out of 76 patients (23.68%) experienced QT interval prolongation, while in the levofloxacin group, 6 out of 70 patients (8.57%) experienced QT interval prolongation; the difference between the 2 groups was statistically significant ( P=0.025). There were no statistically significant differences in other factors between the 2 groups. Univariate regression analysis showed that female ( OR=2.958, 95% CI: 1.144-7.647, P=0.025), myocardial infarction ( OR=2.958, 95% CI: 1.144-7.647, P=0.025), concomitant use of amiodarone ( OR=2.569, 95% CI: 1.042-6.337, P=0.040) and escitalopram were influencing factors of QT interval prolongation. Factors with P<0.2 were entered in the multivariate logistic regression analysis, and the results showed that female ( OR=3.616, 95% CI: 1.240-10.538, P=0.019), hypokalemia ( OR=2.953, 95% CI: 1.263-6.905, P=0.012), and myocardial infarction ( OR=3.026, 95% CI: 1.057-8.666, P=0.039) were independent risk factors for QT interval prolongation. Conclusions:Moxifloxacin is associated with a higher incidence of QT interval prolongation compared to levofloxacin. Female and patients with hypokalemia and myocardial infarction have high risks for QT interval prolongation.