Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Sepsis is a syndrome of systemic inflammatory response in which the body′s response to infection is dysregulated, and is characterized by persistent infection, excessive inflammation and immunosuppression, etc. It often leads to organ dysfunction and can be life threatening, and also a common complication after trauma. The pathogenesis of post-traumatic sepsis is still unclear at present due to the complexity of its etiology, progression and prognosis. Multi-omics technology is a method to combine two or more single omics for comprehensive analysis, which can reveal the interaction network among the disease-associated molecules from multiple perspectives and aspects and is of great significance for the analysis of the pathogenesis of post-traumatic sepsis. To this end, the authors reviewed the research progress on the role of multi-omics technology in elucidating the pathogenesis of post-traumatic sepsis from the perspectives of genomics, transcriptomics, proteomics, metabolomics, single-cell transcriptomics and combination of multi-omics technologies, etc so as to provide a reference for the researches on post-traumatic sepsis.

Objective:To investigate the positive rate and isolate Bordetella pertussis in children with suspected whooping cough and their close family members in Zhejiang Province, and further explore the susceptibility and resistant mechanism of Bordetella pertussis to antibiotics. Methods:A total of 273 nasopharynx swabs specimens from children with suspected whooping cough in Hangzhou Children′s Hospital from May 2022 to October 2022 were collected. The strains were isolated and cultured using charcoal select agar plate. Pertussis target genes were detected by RT-PCR. E-test method was used to detect the sensitivity of Bordetella pertussis strains to different antibiotics. The mechanism of resistance of Bordetella pertussis to macrolides was analyzed by whole genome sequencing. The phylogenetic analysis of isolated strains was based on core genome multilocus sequence typing(cgMLST). Results:Among 273 clinical samples of children with suspected pertussis and their close family members, 168 samples were positive by fluorescence quantitative PCR, accounting for 61.54%, and 30 pertussis strains were successfully isolated with a positive rate of 10.98%. In addition, among the 143 samples of close family members, 54.55% (78/143) samples were positive by RT-PCR and 9.79% (14/143) samples were positive by culture, suggesting that the close family member are important in family transmission of pertussis. Besides, most of the positive samples were from mothers. The results of E-test showed that 96.67%(29/30) strains showed high resistance to azithromycin with MIC value>256 mg/L, and the resistant mechanism of azithromycin was A2047G mutation in 23S rRNA. The phylogenetic analysis based on the cgMSLT showed that the isolated strains were clustered into two new different clades.Conclusions:The positive rate of Bordetella pertussis in close family members is at a high level and the mother may be the main source of infection, which is of great significance for monitoring and laboratory detection of suspected children′s family members. Bordetella pertussis shows high resistance to macrolides in Zhejiang Province, so monitoring of the antimicrobial resistance should be further strengthened to provide theoretical basis for clinical treatment and drug guidance.

Humans ; Asthma/drug therapy* ; Biological Therapy

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

In recent years, the research on the core competence of disaster nursing in China has been relatively active in recent years, but has not yet formed a scale and perfect system. This paper introduces the related concepts of disaster nursing core competence, the development of International Council of Nurses (ICN) disaster nursing core competence framework, summarizes the disaster nursing core competence of different disaster characteristics and rescue groups in China, the evaluation tools of disaster nursing core competence, the cultivation of core competence, and the factors affecting the competence, and puts forward some thoughts and prospects for the construction of disaster nursing core competence in the future.

Inflammatory reaction dominated by defense response will arise against infection and trauma. As an important proinflammatory cytokine, high mobility group box 1 (HMGB1) is widely expressed in all nuclear cells to mediate the inflammatory response. However, the biological functions of HMGB1 in inflammation vary depending on the type of HMGB1 protein modification and the localization in the cell. HMGB1 protein will be modified as acetylation of lysine residues, methylation of lysine residues, oxidation of cysteine residues, phosphorylation of serine residues, glycosylation of asparagine residues, adenosine diphosphate-ribosylation and lactylation of the protein in the nucleus, migrate from the nucleus to the cytoplasm, and release into the extracellular compartment. Extracellular HMGB1 can bind to receptors for advanced glycation end products (RAGE) and Toll-like receptors, activate cells and regulate inflammatory responses. The authors review the research progress in regulatory mechanism of HMGB1 in inflammation response from aspects of its post-translational modifications, releases, biological roles and binding receptors, hoping to provide theoretical basis for finding the targets of inflammation intervention.

Objective:To evaluate the effect of propofol on proliferation, invasion and migration of human melanoma cells and role of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/matrix metalloproteinase (MMP) signaling pathway.Methods:SKMEL-5 cells were cultured in vitro and divided into 4 groups ( n=36 each) using the random number table method: control group (group C), propofol group (group P), COX-2 overexpression group (group COX-2), and COX-2 overexpression plus propofol group (group COX-2+ P). Propofol at the final concentration of 60 μmol/L was added in group P. The COX-2 overexpression plasmid pcDNA3.1-COX-2 was transfected into SKMEL-5 cells in group COX-2 and group COX-2+ P, and propofol at the final concentration of 60 μmol/L was added in group COX-2+ P.After incubation for 48 h, the cell proliferation rate was determined by CCK-8 method, the cell invasion and migration ability was determined by Transwell assay, the expression of COX-2 in cells was detected by Western blot, the expression of COX-2 mRNA in cells was detected by quantitative real-time polymerase chain reaction, and the concentrations of serum PGE2, MMP-2 and MMP-9 were determined by enzyme-linked immunosorbent assay. Results:Compared with group C, the cell proliferation rate was significantly decreased, the number of cell invasion and migration was decreased, the expression of COX-2 protein and mRNA was down-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were decreased in group P, and the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2 ( P<0.05). Compared with group P, the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2+ P ( P<0.05). Conclusions:Propofol can inhibit the proliferation, invasion and migration of human melanoma cells, and the mechanism may be related to inhibition of the COX-2/PGE2/MMP signaling pathway.