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: We previously found that the incidence of sarcopenia increased with declining glucose metabolism of muscle in patients with treatment-naïve diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the relationship between sarcopenia and muscle glucometabolism using 18 F-FDG PET/CT at baseline and end-of-treatment, analyze the changes in these parameters through treatment, and assess their prognostic values. Materials and Methods: The records of 103 patients with DLBCL (median 54 years [range, 21–76]; male:female, 50:53) were retrospectively reviewed. Skeletal muscle area at the third lumbar vertebral (L3) level was measured, and skeletal muscle index (SMI) was calculated to determine sarcopenia, defined as SMI < 44.77 cm 2 /m 2 and < 32.50 cm 2 /m 2 for male and female, respectively. Glucometabolic parameters of the psoas major muscle, including maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), were measured at L3 as well. Their changes across treatment were also calculated as ΔSMI, ΔSUVmax, and ΔSUVmean; Δbody mass index was also calculated. Associations between SMI and the metabolic parameters were analyzed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified. Results: The incidence of sarcopenia was 29.1% and 36.9% before and after treatment, respectively. SMI (P = 0.004) was lower, and sarcopenia was more frequent (P = 0.011) at end-of-treatment than at baseline. The SUVmax and SUVmean of muscle were lower (P < 0.001) in sarcopenia than in non-sarcopenia at both baseline and end-of-treatment. ΔSMI was positively correlated with ΔSUVmax of muscle (P = 0.022). Multivariable Cox regression analysis showed that sarcopenia at end-of-treatment was independently negatively associated with PFS (adjusted hazard ratio [95% confidence interval], 2.469 [1.022–5.965]), while sarcopenia at baseline was independently negatively associated with OS (5.051 [1.453–17.562]). Conclusion Sarcopenic patients had lower muscle glucometabolism, and the muscular and metabolic changes across treatment were positively correlated. Sarcopenia at baseline and end-of-treatment was negatively associated with the prognosis of DLBCL.

Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.
Humans ; Adolescent ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Acute Disease ; Prognosis ; Leukemia-Lymphoma, Adult T-Cell/therapy* ; Nuclear Pore Complex Proteins

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

High-intensity interval training (HIIT) has proven to be a time-saving and efficient exercise strategy. Compared with traditional aerobic exercise, it can provide similar or even better health benefits. In recent years, a number of studies have suggested that HIIT could be used as a potential exercise rehabilitation therapy to improve cognitive impairment caused by obesity, diabetes, stroke, dementia and other diseases. HIIT may be superior to regular aerobic exercise. This article reviews the recent research progress on HIIT with a focus on its beneficial effect on brain cognitive function and the underlying mechanisms. HIIT may become an effective exercise for the prevention and/or improvement of brain cognitive disorder.
Cognition ; Exercise ; High-Intensity Interval Training ; Humans ; Obesity ; Stroke

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.
Animals ; Apoptosis ; Brucea/chemistry* ; Glycogen Synthase Kinase 3 ; Humans ; Jurkat Cells ; Mice ; Phosphatidylinositol 3-Kinases/genetics* ; Plant Oils/pharmacology* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Proto-Oncogene Proteins c-akt/genetics* ; Seeds/chemistry* ; Signal Transduction

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

OBJECTIVE: To study the value of anti-neutrophil cytoplasmic antibody (ANCA) in assessing the severity of bronchiolitis obliterans (BO) in children. METHODS: A prospective analysis was performed on 59 children who were diagnosed with BO from June 2009 to October 2014. ELISA was used to measure the concentrations of myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA in serum. According to the results of ELISA, the children were divided into three groups: double-negative ANCA (n=22), single-positive ANCA (n=17), and double-positive ANCA (n=20). The three groups were compared in terms of the scores of BO risk factors, clinical symptoms, chest high-resolution computed tomography (HRCT), and lung pathology on admission, as well as the changes in the expression level of ANCA and the scores of clinical symptoms and chest HRCT over time. RESULTS: Compared with the double-negative ANCA group, the double-positive ANCA group had a significantly higher score of BO risk factors (P<0.05), and the single-positive ANCA group and the double-positive ANCA group had significantly higher scores of clinical symptoms, chest HRCT, and lung pathology (P<0.05). The children were followed up for 6 months after discharge, and there were significant reductions in MPO-ANCA and PR3-ANCA titers from admission and discharge to the end of follow-up (P<0.05), as well as a significant reduction in the score of clinical symptoms from admission to the end of follow-up (P<0.05), while there was no significant change in the score of chest HRCT from admission to the end of follow-up (P>0.05). The single-positive ANCA and double-positive ANCA groups still had a significantly higher score of clinical symptoms than the double-negative ANCA group (P<0.05). CONCLUSIONS The expression level of ANCA is correlated with the severity of BO in children and thus has certain clinical significance in disease evaluation.
Antibodies, Antineutrophil Cytoplasmic ; Bronchiolitis Obliterans ; Child ; Humans ; Myeloblastin ; Peroxidase ; Prospective Studies

Objective: Moxifloxacin (MFX) shows good activity against and can be a possible antibiotic therapy to treat infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against using zebrafish (ZF) model . Methods: A formulation of labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. Results: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. Conclusion MFX showed limited efficacy against using ZF model. Its activity needs to be confirmed.
Animals ; Anti-Bacterial Agents ; pharmacology ; Disease Models, Animal ; Moxifloxacin ; pharmacology ; Mycobacterium Infections, Nontuberculous ; drug therapy ; Mycobacterium abscessus ; drug effects ; Zebrafish