OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

OBJECTIVE: To observe the efficacy and safety of 21-day venetoclax (VEN) plus azacitidine (AZA) (21-day VA) in newly diagnosed unfit acute myeloid leukemia (AML) patients in the real-world. METHODS: The clinical data of patients with unfit-AML who received 21-day VA regimen from December 2020 to July 2024 in our center and completed at least 1 cycle of therapeutic effect assessment was retrospectively collected to analyze the safety, efficacy and its influencing factors. RESULTS: A total of 59 patients were enrolled in our study, with a median age of 67(48-87) years old. After 1 cycle of therapy, the composite complete remission (cCR) rate was 74.5%, 54.2% of cases were negative for minimal residual disease (MRD). Among them, the MRD negative rate of patients with NPM1 mutation was significantly higher than that of patients without NPM1 mutation ( P =0.032). The median follow-up of patients was 19(2-38) months, the best cCR and MRD negative rates were 78% and 64.4%, respectively, the median overall survival (OS) time was 12 months, and the median progression free survival (PFS) time was 5 months. Multivariate Cox regression analysis showed less than 4 cycles of VA chemotherapy were independent risk factor for PFS and OS ( P < 0.05). After achieving remission, anemia and thrombocytopenia improved with the increase of the number of chemotherapy cycle. CONCLUSION In real-world, 21-day VA regimen still shows significant efficacy in the treatment of newly diagnosed unfit-AML, without adversely affecting remission rate and MRD negative rate of the first cycle.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Middle Aged ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Azacitidine/therapeutic use* ; Aged, 80 and over ; Male ; Female ; Retrospective Studies ; Nucleophosmin ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Remission Induction ; Mutation ; Treatment Outcome

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To discuss the effect of Xuebijing on brain tissue damage and immune imbalance of helper T lymphocyte 17(Th17)/regulatory T lymphocyte(Treg)in cerebrospinal fluid(CSF)of the N-methyl-D-aspartate(NMDA)receptor encephalitis model mice,and to clarify its therapeutic effect.Methods:Sixty healthy male C57BL/6J mice were randomly divided into control group,model group,low dose of Xuebijing group,and high dose of Xuebijing group,and there were 15 mice in each group.Except for control group,the mice in the other three groups were injected with the antigen combined with immunostimulation to establish the NMDA receptor encephalitis models.The mice in low and high doses of Xuebijing groups were injected intraperitoneally with 5 and 10 mL·kg-1 of Xuebijing injection,respectively.HE staining was used to observe the pathomorphology of brain tissue of the mice in various groups;TUNEL assay was used to detect the apoptotic rates of the neurons in hippocampus CA1 region of brain tissue of the mice in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of interleukin(IL)-6,IL-10,IL-17,and transforming growth factor β(TGF-β)in serum of the mice in various groups;flow cytometry was used to detect the percentages of Th17 and Treg cells in CSF of the mice in various groups;Western blotting method was used to detect the expression levels of retinoic acid-related orphan receptor γt(RORγt),forkhead box protein 3(Foxp3),IL-10,and IL-17 proteins in brain tissue of the mice in various groups;immunohistochemistry method was used to detect the rates of IL-17 and Foxp3 positive cells in brain tissue of the mice in various groups.Results:The HE staining results showed that the hippocampus CA1 region of brain tissue of the mice in control group had a clear structure without obvious lesions;compared with control group,the mice in model group showed partial pyramidal cell shrinkage,elongation of apical dendrites,loss of a few neurons,and sparse tissue in the hippocampus CA1 region of brain tissue;compared with model group,the mice in low and high doses of Xuebijing groups showed that the damage of the cells in the hippocampus CA1 region of brain tissue was decreased,and the morphological recovery,more orderly arrangement,and more significant improvement could be seen in hippocampus CA1 region of the mice in high dose of Xuebijing group.The TUNEL assay results showed that compared with control group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in model group was significantly increased(P<0.05);compared with model group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05);compared with low dose of Xuebijing group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in high dose of Xuebijing group was significantly decreased(P<0.05).The ELISA results showed that compared with control group,the levels of IL-6 and IL-17 in serum of the mice in model group were significantly increased(P<0.05),while the levels of IL-10 and TGF-β were significantly decreased(P<0.05);compared with model group,the levels of IL-6 and IL-17 in serum of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the levels of IL-10 and TGF-β were significantly increased(P<0.05);compared with low dose of Xuebijing group,the levels of IL-6 and IL-17 in serum of the mice in high dose of Xuebijing group were significantly decreased(P<0.05),while the levels of IL-10 and TGF-β were significantly increased(P<0.05).The flow cytometry results showed that compared with control group,the percentage of CD4+IL-17A+Th17 cells in CSF of the mice in model group was significantly increased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly decreased(P<0.05);compared with model group,the percentages of CD4+IL-17A+Th17 cells in CSF of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly increased(P<0.05);compared with low dose of Xuebijing group,the percentage of CD4+IL-17A+Th17 cells in CSF of the mice in high dose of Xuebijing group was significantly decreased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in model group were significantly increased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly decreased(P<0.05);compared with model group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly increased(P<0.05);compared with low dose of Xuebijing group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in high dose of Xuebijing group were significantly decreased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly increased(P<0.05).The immunohistochemistry results showed that compared with control group,the rate of IL-17 positive cells in brain tissue of the mice in model group was significantly increased(P<0.05),while the rate of Foxp3 positive cells was significantly decreased(P<0.05);compared with model group,the rates of IL-17 positive cells in brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the rates of Foxp3 positive cells were significantly increased(P<0.05);compared with low dose of Xuebijing group,the rate of IL-17 positive cells in brain tissue of the mice in high dose of Xuebijing group was significantly decreased(P<0.05),while the rate of Foxp3 positive cells was significantly increased(P<0.05).Conclusion:Xuebijing can effectively ameliorate the brain tissue injury,regulate the cytokine levels,and intervene in immune imbalance of Th17/Treg in the mice with anti-NMDA receptor encephalitis.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Objective To observe the therapeutic effect and mechanism of astragalus polysaccharide on non-Hodgkin's lymphoma(NHL).Methods Three kinds of NHL cells,WSU-DLCL2,BJAB and SP53,were cultured and treated with different concentrations(0,5,10,50,100,200,400 μmol/L)of astragalus polysaccharide.The cell viability was detected by cell counting kit-8(CCK-8)method to screen the optimal concentration of astragalus polysaccharide and the cells sensitive to astragalus polysaccharide.WSU-DLCL2 cells were divided into control group,astragalus polysaccharide group,BMS-1[programmed death molecule 1(PD-1)/programmed death ligand 1(PD-L1)pathway inhibitor]group,astragalus polysaccharide+BMS-1 group.The colony formation,apoptosis,migration and invasion of each group were detected,and the protein expression of PD-1/PD-L1 signaling pathway was detected by Western Blot.After co-culture of WSU-DLCL2 cells and CD8+T cells,the percentage and apoptosis of CD8+T cells,and the levels of interferon(IFN)-γ and tumor necrosis factor(TNF)-α in the supernatant were detected.Results The follow-up experiments selected 200 μmol/L astragaloside to treat WSU-DLCL2 cells.Compared with the control group,the number of WSU-DLCL2 cell colony formation,the number of migrating WSU-DLCL2 cells,the number of invading WSU-DLCL2 cells,the apoptosis rate of CD8+T cells,and the protein expression levels of PD-1 and PD-L1 in WSU-DLCL2 cells were significantly decreased in the Astragali polysaccharide group,the BMS-1 group and the Astragali polysaccharide+BMS-1 group(P＜0.05),and the apoptosis rate of WSU-DLCL2 cells,the proportion of CD8+T cells,and the levels of IFN-γ and TNF-α in the supernatant of co-culture system were significantly increased(P＜0.05);compared with astragali polysaccharide group and BMS-1 group,the number of WSU-DLCL2 cell colony formation,migrating WSU-DLCL2 cells,invading WSU-DLCL2 cells,CD8+T-cell apoptosis rate,and protein expressions of PD-1,PD-L1 in WSU-DLCL2 cells were further decreased in astragali polysaccharide+BMS-1 group(P＜0.05),and the rate of WSU-DLCL2 cell apoptosis,the proportion of CD8+T-cells,and the levels of IFN-γ,TNF-α in the supernatant of co-culture system were significantly further elevated(P＜0.05).Conclusion Astragalus polysaccharide can inhibit NHL cell proliferation,migration and invasion,promote its apoptosis and reduce immune escape,and its mechanism may be related to the inhibition of PD-1/PD-L1 signaling pathway.

Objective To investigate the therapeutic effect of Xuebijing on anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis mice and its effect on the changes of helper T cell 1(Th1)/helper T cell 2(Th2).Methods The experimental groups included control group,model group,low-dose Xuebijing(low-XBJ)group,high-dose Xuebijing(high-XBJ)group,with 10 mice in each group,except the control group,the other 3 groups of mice were treated with antigen injection and immune stimulation to establish anti-NMDAR encephalitis models,the mice in the low-XBJ and high-XBJ groups were intraperitoneally injected with 5 ml/kg and 10 ml/kg of Xuebijing injection,respectively,once every 12 hours for 3 consecutive days;After 2 weeks,HE staining was used to observe the pathological changes of mice brain tissue,Nissl staining was used to observe the morphological changes of mice neurons,TUNEL staining was used to detect the apoptosis of mice neurons,ELISA was used to detect the contents of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4 and interferon-γ(IFN-γ)in serum and cerebrospinal fluid of mice,immunohistochemical staining and Western blotting were used to detect the expression of IFN-γ and IL-4 in brain tissue,flow cytometry was used to detect the distribution of Th1 and Th2 cells in peripheral blood,and the ratio of Th1/Th2 was calculated.Results Compared with the model group,hippocampal tissue damage was improved in low-XBJ group and high-XBJ group,the morphological changes of neurons were small,the morphology of Nissl bodies was more complete and the number of Nissl bodies was increased,the TUNEL positive rate of neurons decreased,the contents of TNF-α,IL-1β and IFN-γ in serum and cerebrospinal fluid decreased while the content of IL-4 increased,the percentage of IFN-γ positive cells and the relative expression of protein in brain tissue decreased,the percentage of IL-4 positive cells and the relative expression of protein increased,the proportion of cluster of differentiation(CD)4+IFN-γ+labeled Th1 cells and the ratio of Th1/Th2 in peripheral blood decreased,and the proportion of CD4+IL-4+labeled Th2 cells in peripheral blood of mice in high-XBJ group increased,the differences were statistically significant(P＜0.05).In addition,compared with the low-XBJ group,the improvement effect of the above detection indicators in the high-XBJ group was more obvious,and the differences were statistically significant(P＜0.05).Conclusion Xuebijing can improve hippocampal neuronal damage in anti-NMDAR encephalitis mice,which may play a therapeutic role by reducing the expression of IFN-γ,promoting the expression of IL-4 and maintaining the balance of Th1/Th2 cells.