Objective:To investigate the incidence of PTPN11 gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia(AML),and analyze its clinical characteristics.Methods:Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations,and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University,Changzhou Second People's Hospital,Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.Results:Among 451 primary adult AML patients,the PTPN11 gene mutation was detected in 34 cases,and the mutation rate was 7.5％.In the 34 patients,37 PTPN11 alterations were found,which were exclusively missense mutations affecting residues located within the N-SH2(31 cases)and PTP(6 cases)domains and clustered overwhelmingly in exon 3.The platelet count of PTPN11 mutation patients was 76.5(23.5,119.0)× 109/L,which was significantly higher than 41.0(22.0,82.5)×109/L of wild-type patients(P＜0.05).While,there were no significant differences in sex,age,peripheral white blood cell count,hemoglobin,and bone marrow blast between PTPN11 mutation and wild-type patients(P＞0.05).In FAB subtypes,PTPN11 mutations were mainly distributed in M5,followed by M2 and M4,less frequently in M3 and M6.There was no significant difference in the distribution of FAB subtypes between PTPN11 mutation and wild-type patients(P＞0.05).A total of 118 AML patients were detected positive fusion gene,among which patients with PTPN11 mutations had a higher incidence of positive MLL-AF6 than wild-type ones(P＜0.01).97.1％of 34 patients with PTPN11 mutations were accompanied by other mutations,in descending order,they were respectively NPM1(38.2％),NRAS(32.4％),FLT3-ITD(32.4％),DNMT3A(32.4％)and KRAS(23.5％),etc.Conclusion:PTPN11 mutation has a certain incidence in AML patients and is clustered overwhelmingly in exon 3.ALL of them are exclusively missense mutations,and most often present in conjunction with NPM1 mutations.FAB typing of PTPN11 mutation is mostly manifested as M5 subtype,which is associated with higher platelet counts.

Objective:To establish a model to predict the overall survival(OS)rate of patients with diffuse large B-cell lymphoma(DLBCL)based on systemic inflammatory indicators,and study whether the new model combined with inflammatory related parameters is more effective than the conventional model using only clinical factors to predict the OS of patients with DLBCL.Methods:The clinical data of 213 patients with DLBCL were analyzed retrospectively.Backward stepwise Cox regression analysis was used to screen independent prognostic factors related to OS,and a nomogram for predicting OS was constructed based on these factors.Akaike information criterion(AIC)and Bayesian information criterion(BIC)were used to evaluate the fitting of the model,the consistency index(C-index),area under receiver operating characteristic(ROC)curve(AUC)and calibration curve were used to evaluate the prediction accuracy of nomogram,and decision curve analysis(DCA)and Kaplan Meier curve were used to evaluate the clinical practicability of nomogram.Results:Multivariate analysis confirmed that age,ECOG PS score,serum lactate dehydrogenase(LDH)level,systemic immune inflammatory index(SII),and prognostic nutritional index(PNI)were used to construct the nomogram.The AIC and BIC of the nomogram were lower than the International Prognostic Index(IPI)and the National Comprehensive Cancer Network(NCCN)-IPI,indicating that the nomogram had better goodness of fit.The C-index and AUC of the nomogram were higher than IPI and NCCN-IPI,indicating that the prediction accuracy of the nomogram had been significantly improved,and the calibration curve showed that the prediction results were in good agreement with the actual survival results.DCA showed that the nomogram had better clinical net income.Kaplan Meier curve showed that patients could be well divided into low-risk,medium-risk and high-risk groups according to the nomogram score(P＜0.001).Conclusion:The nomogram combined with inflammatory indicators can accurately predict the individual survival probability of DLBCL patients.

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Aim To explore he preventive and therapeutic effects of Tongbu-fangchan prescription on aceylcholine-calcium chloride (Ach-CaCl

Fibrosis is a repair response initiated by tissues and organs after injury, and is a self-protection mechanism of the body. It has been found that endothelium-to-interstitial transdifferentiation (EndMT) is involved in the physiological and pathological processes of various organ fibrosis, which has become a focus of the research on fibrotic diseases. In recent years, the study has found that EndMT plays an important role in many pathological processes in cardiovascular system, lungs, kidneys, liver, pancreas fibrosis, and so on. This article summarizes EndMT regulatory mechanism and its role in each organ fibrosis, as well as the related treatment progress of EndMT targets, so as to provide new targets for prevention and control of organ fibrosis.

PURPOSE: Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS. METHODS: A retrospective cohort study was conducted on patients diagnosed with DVT following a lower extremity orthopedic surgery before being transferred to the rehabilitation ward from May 2017 to May 2022. Patients with unilateral lower limb comminuted para-articular fractures, transferred to rehabilitation ward for further treatment within 3 weeks after operation, followed up more than 12 weeks since initial manual physiotherapy, and diagnosed DVT by ultrasound before rehabilitation course were included in the study. Patients with polytrauma, without evidence of previous peripheral vascular disease or incompetence, had medication for thrombosis treatment or prophylaxis before the operation, detected with paralysis due to nervous system impairment, infected after operation during the regime, or with acute progression of DVT were excluded. The included patients were randomized to the standard physiotherapy and the SPS integrated groups for observation. Associated DVT and pulmonary embolism data were collected during the physiotherapy course to compare the groups. SSPS 28.0 and GraphPad Prism 9 were used for data processing. A p < 0.05 was set significant difference. RESULTS: In total of 154 patients with DVT participating in this study, 75 of them were treated with additional SPS for postoperative rehabilitation. The participants in the SPS group showed improved range of motion (12.3° ± 6.7°). However, in the SPS group, there was no difference in thrombosis volume between the start and termination (p = 0.106, p = 0.787, respectively), although difference was seen intra-therapy (p < 0.001). Contingency analysis revealed the pulmonary embolism incidence (OR = 0.703) in the SPS group compared to the mean physiotherapy. CONCLUSION The SPS technique is a safe and reliable option to prevent potential joint stiffness without aggravating the risk of distal DVT for postoperative patients suffering from relevant trauma.
Humans ; Venous Thromboembolism/prevention & control* ; Venous Thrombosis/etiology* ; Retrospective Studies ; Pulmonary Embolism/complications* ; Lower Extremity ; Risk Factors

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice ; Animals ; Humans ; Hepatitis, Autoimmune/pathology* ; Signal Transduction ; Disease Models, Animal ; Stem Cells

Considering the undesirable metabolic stability of our recently identified NNRTI 5 (t_1/2 = 96 min) in human liver microsomes, we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine. This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity. The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes (t_1/2 = 2754 min), which was about 29-fold longer than that of 5 (t_1/2 = 96 min). This compound conferred picomolar inhibition of WT HIV-1 (EC₅₀ = 0.9 nmol/L) and low nanomolar activity against five clinically drug-resistant mutant strains. It maintained particularly low cytotoxicity (CC₅₀ = 264 μmol/L) and good selectivity (SI = 256,438). Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138. Also, compound 9g was characterized by good safety profiles. It displayed no apparent inhibition of CYP enzymes and hERG. The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg. These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia