Objective:This study aims to provide insights into the clinical features of anti-melanoma differentiation-associated protein-5(MDA5)-positive dermatomyositis (MDA5-DM) patients with fatal outcomes, leveraging pathogenic microbiota metagenomic analysis, to guide the clinical assessment and treatment choices.Methods:From January 2020 to August 2023, deceased patients diagnosed with MDA5-DM were identified at the Department of Rheumatology and Immunology, the Second Affiliated Hospital of Xi ′an Jiaotong University. Clinical data were retrospectively collected and analyzed using Mann Whitney U test and Fisher ′s exact test to summarize risk factors and treatment assessment for MDA5-DM patients with fatal outcomes. Results:①The proportion of male patients was higher than females among MDA5-DM patients with fatal outcomes, which differed from the incidence pattern, possibly associated with smoking and gender proportions (6/11 vs. 0/7, P=0.037). ②94%(17/18) patients presented initially with elevated ferritin levels [(1 350±942)ng/ml] and CRP [(47±36)mg/L]. ③All patients (18/18) exhibited early involvement of the upper lung lobes, including multiple nodules in 9/18, ground-glass opacities in 5/18, and solitary nodules in 4/18. ④Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid was negative in 4/16 cases, with cytomegalovirus and pneumocystis jirovecii being the most commonly detected pathogens in 5/16 cases each. ⑤89%(16/18) of patients continued to have lymphocyte counts persistently <0.5×10 9/L irrespective of treatment. Conclusion:Smoking may have adverse effects on male MDA5 patients. Early involvement of the upper lobe of the lungs is more common in MDA5 antibody positive deaths, and persistent lymphocyte depletion is an important factor in poor response. Enhancing mNGS analysis of bronchoalveolar lavage fluid and vigilance towards cytomegalovirusand Pneumocystis jirovecii could provide valuable clinical guidance.

Objective:To evaluate the diagnostic value of targeted next-generation sequencing (tNGS) of throat swab samples for detecting community-acquired respiratory viruses (CARV) in patients with hematological diseases.Methods:Clinical and laboratory data from 64 episodes involving patients with hematological diseases and suspected infections—who underwent both pharyngeal swab tNGS and CARV polymerase chain reaction (PCR) testing concurrently—were retrospectively analyzed. The cases were drawn from the Department of Hematology, Peking University People’s Hospital, between September 2023 and April 2024. Concordance between tNGS and CARV PCR results, as well as the diagnostic performance of tNGS in detecting CARV, were evaluated.Results:Among the 64 episodes, 29 were clinically diagnosed with respiratory tract infections, including one case of cytomegalovirus pneumonia and 28 CARV-positive cases. The remaining 35 episodes involved patients with fever or respiratory symptoms attributed to other causes, including 14 with extrapulmonary infections and 21 with noninfectious etiologies. The median follow-up duration was 215.5 days (range: 7-271 days). PCR detected 24 strains of seven CARV types, whereas tNGS detected 25 strains of eight CARV types. Using PCR results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of tNGS were 85.0%, 88.6%, 77.3%, 92.9%, and 87.5%, respectively. The two methods showed good concordance (Kappa=0.717, P<0.001) . Conclusion:Pharyngeal swab tNGS may serve as a viable alternative to PCR for diagnosing CARV infections in patients with hematological diseases.

Objective:To evaluate the diagnostic value of targeted next-generation sequencing (tNGS) of throat swab samples for detecting community-acquired respiratory viruses (CARV) in patients with hematological diseases.Methods:Clinical and laboratory data from 64 episodes involving patients with hematological diseases and suspected infections—who underwent both pharyngeal swab tNGS and CARV polymerase chain reaction (PCR) testing concurrently—were retrospectively analyzed. The cases were drawn from the Department of Hematology, Peking University People’s Hospital, between September 2023 and April 2024. Concordance between tNGS and CARV PCR results, as well as the diagnostic performance of tNGS in detecting CARV, were evaluated.Results:Among the 64 episodes, 29 were clinically diagnosed with respiratory tract infections, including one case of cytomegalovirus pneumonia and 28 CARV-positive cases. The remaining 35 episodes involved patients with fever or respiratory symptoms attributed to other causes, including 14 with extrapulmonary infections and 21 with noninfectious etiologies. The median follow-up duration was 215.5 days (range: 7-271 days). PCR detected 24 strains of seven CARV types, whereas tNGS detected 25 strains of eight CARV types. Using PCR results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of tNGS were 85.0%, 88.6%, 77.3%, 92.9%, and 87.5%, respectively. The two methods showed good concordance (Kappa=0.717, P<0.001) . Conclusion:Pharyngeal swab tNGS may serve as a viable alternative to PCR for diagnosing CARV infections in patients with hematological diseases.

Objective:This study aims to provide insights into the clinical features of anti-melanoma differentiation-associated protein-5(MDA5)-positive dermatomyositis (MDA5-DM) patients with fatal outcomes, leveraging pathogenic microbiota metagenomic analysis, to guide the clinical assessment and treatment choices.Methods:From January 2020 to August 2023, deceased patients diagnosed with MDA5-DM were identified at the Department of Rheumatology and Immunology, the Second Affiliated Hospital of Xi ′an Jiaotong University. Clinical data were retrospectively collected and analyzed using Mann Whitney U test and Fisher ′s exact test to summarize risk factors and treatment assessment for MDA5-DM patients with fatal outcomes. Results:①The proportion of male patients was higher than females among MDA5-DM patients with fatal outcomes, which differed from the incidence pattern, possibly associated with smoking and gender proportions (6/11 vs. 0/7, P=0.037). ②94%(17/18) patients presented initially with elevated ferritin levels [(1 350±942)ng/ml] and CRP [(47±36)mg/L]. ③All patients (18/18) exhibited early involvement of the upper lung lobes, including multiple nodules in 9/18, ground-glass opacities in 5/18, and solitary nodules in 4/18. ④Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid was negative in 4/16 cases, with cytomegalovirus and pneumocystis jirovecii being the most commonly detected pathogens in 5/16 cases each. ⑤89%(16/18) of patients continued to have lymphocyte counts persistently <0.5×10 9/L irrespective of treatment. Conclusion:Smoking may have adverse effects on male MDA5 patients. Early involvement of the upper lobe of the lungs is more common in MDA5 antibody positive deaths, and persistent lymphocyte depletion is an important factor in poor response. Enhancing mNGS analysis of bronchoalveolar lavage fluid and vigilance towards cytomegalovirusand Pneumocystis jirovecii could provide valuable clinical guidance.

OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

Objective: To determine the expression of TAZ and its role in angiogenesis in gastric carcinoma. Methods: Immunohistochemical staining was performed to investigate the expression of TAZ and to determine whether a direct relationship exists between TAZ and β-catenin. Transfection with TAZ overexpression plasmid in MKN28 cells was conducted to induce exogenous expression of TAZ and a TAZ knockdown plasmid was transfected into MGC803 cells to reduce TAZ levels. The effects on endothelial cell formation, proliferation, and migration were determined by Matrigel three-dimensional culture, MTT proliferation assay and Transwell migration assay. In addition, the expression of TAZ and β-catenin in transfected gastric cancer cells was detected by Western blot. Results: Immunohistochemistry showed that TAZ protein was expressed in 64 of 150 gastric cancer sample tissues (43%), TAZ was localized in the nucleus, and its expression was associated with tumor grade, TNM stage, metastasis, and microvessel density (MVD) (P<0.05). In addition, the expression frequency of β-catenin in the TAZ positive group was 67.2%, which was significantly higher than that in the TAZ negative group, and the expression of TAZ was positively correlated with β-catenin. After transfection, TAZ overexpression increased the expression of β-catenin and enhanced HUVECs tube formation, proliferation, and migration. In the MGC803 cells transfected with the knockdown plasmid, β-catenin levels were decreased and HUVECs motility was inhibited. Conclusions: TAZ may promote angiogenesis in gastric cancer by promoting β-catenin expression.

Objective To investigate the effect on occupational failure and psychological withdraw behavior of group occupational characteristics in nurses of Pearl River Delta. Methods Questionnaire approach including demographic variables, job autonomy of occupational characteristics, work routinization, occupational exposure risk, occupational stress, occupational failure and psychological withdraw behavior were investigated in clinical nurses in 20 hospitals of Pearl River Delta. Results Group occupational characteristics in nurses influence directly on the psychological withdraw behavior. Occupational failure was partly involve in the relationships such as job autonomy of occupational characteristics and psychological withdraw behavior, work routinization and psychological withdraw behavior, occupational exposure risk and psychological withdraw behavior, occupational stress and psychological withdraw behavior. Conclusions Relative to other professions, group occupational characteristics in nurses cause higher occupational failure rate, and the psychological withdraw behavior in nurses is obviously.Attention should be taken from organizational leadership level to personal level.It is eager to take appropriate measures to relieve the occupational failure in nurses.

How to effectively using the electronic health records (EHR) in contracted family doctors service was studied according to the new model of HER-based community medical service with community health service station as a center in combination with large hospitals,and suggestions were put forward for the solution of problems in contracted family doctor service,namely establishing and perfecting the community health service system,enlarging the scale of HER,strengthening the construction of general doctors team,and training the technically competent community health service staff.

Objective. To determine the effects of HOE 694, a new and potent Na＋ -H＋ exchanger blocker, on transient inward current (Iti) and Na＋ -Ca2＋ exchange during hypoxia-reoxygenation in guinea pig cardiomyocytes. Methods. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique. Results. In the absence of HOE 694, hypoxia-reoxygenation induced Iti in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10～ 50 μ mol/L), the incidence of Iti observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P0.05 vs control respectively. The Na＋-Ca2＋ exchange current was unaffected by HOE 694 under normoxic condition. However, when cells were pretreated with 10 μ mol/L HOE 694 for 10 min, then subjected to hypoxia condition, the Na＋  Ca2＋ exchange current was significantly inhibited. Conclusions. Blockade of the Na＋ -H＋ exchange by HOE 694 could reduce Ca2＋ overload upon hypoxia-reoxygenation, and inhibition of Na＋ -H＋ exchange may also indirectly decrease Na＋ -Ca2＋ exchange activity during hypoxia.