Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Objective:To investigate the effects of pulmonary rehabilitation on anxiety/depression and subjective/objective sleep quality of elderly patients with stable chronic obstructive pulmonary disease(COPD).Methods:From February 2018 to February 2019, 120 elderly patients with stable COPD were selected and randomly divided into the experimental group (pulmonary rehabilitation exercise combined with conventional COPD treatment) and the control group (simple COPD conventional treatment). Sixty cases in each group were intervened for 8 weeks. Before and after treatment, Hamilton anxiety scale (HAMA) was used to evaluate anxiety, Hamilton depression scale(HAMD)was used to evaluate depression, Pittsburgh sleep quality index(PSQI)and sleep log were used to evaluate subjective sleep quality, and objective sleep quality was monitored by multi-channel sleep monitor.SPSS 21.0 software was used to analyze and process the data. Chi square test, independent sample t test and paired t test were used for statistical analysis. Results:After 8 weeks of intervention, the HAMA and HAMD scores of the experimental group were lower than those of the control group (HAMA: (7.57±3.19) vs (10.15±4.89), t=-3.428, P=0.001; HAMD: (8.22±4.73) vs (10.60±6.49), t=-2.300, P=0.023). COPD patients with anxiety decreased (χ 2=7.566, P=0.006). After treatment, the subjective sleep latency of the experimental group was shorter than that of the control group ((42.00±9.88)min vs (47.25±10.27)min, t=-2.854, P=0.005). The subjective sleep efficiency was higher than that of the control group ((76.00±4.50)% vs (74.00±5.20)%, t=2.272, P=0.025), and the objective sleep latency was shorter than that of the control group ((28.02±5.59)min vs (32.95±6.21)min, t=-4.575, P<0.05). Conclusion:Pulmonary rehabilitation exercise can improve the anxiety and depression of elderly patients with stable COPD, and improve the subjective and objective sleep quality.

This paper summarized training status of the Master of Nursing Specialist (MNS) at home and abroad,described and analyzed the cultivation program at home and abroad,and discussed the problems about cultivation objective, enrollment, course system, specialty orientation, clinical training model, teaching method, connotation of practical ability, teachers strength, evaluation and assessment in cultivation of MNS in China. Then MNS training program is proposedso as to provide references for the future cultivation program of MNS in China.

Objective To investigate the role of endogenous Hydrogen Sulfide (H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking.Methods Male SD rats were randomly divided into a control group (breathing fresh air) and a passive smoking group [cigarette smoking (CS) passively] ,with 18 rats in each group.Six rats in each group were randomly intraporitoneally injected with normal saline, sodium hydrosulfide (NailS) or propargylglycine (PPG, an irreversible inhibitor of cystathionine-γ-lyase).The animals were divided into six subgroups,ie.Con group, Naris group, and PPG group, CS group, CS + Naris group, and CS + PPG group.After 4 months,lung histological change and airway tension were measured.The H2 S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay.The expression of cystathionine-γ-lyase (CSE) was measured by western blot.Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group(P < 0.05) ; the H2S levels of plasma were significantly higher in GS group,NariS group and CS + Naris group,and much lower in PPG group (P < 0.05, respectively).Compared with CS group, the H2 S levels of plasma were significantly higher in CS + Naris group, and much lower in CS + PPG group (P < 0.05, respectively).The H2S level of lung tissue in each group had no significant difference (P > 0.05).Compared with Con group, score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to Ach and KCI was significant augmented in CS group.Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS + NariS group(P < 0.05), and vise versa in CS + PPG group (P < 0.01).Conclusion H2 S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airway inflammation and airway responsiveness.

OBJECTIVETo investigate the role of calcineurin (CaN) in the lung fibroblast proliferation and collagen synthesis induced by basic fibroblast growth factor (bFGF).

METHODSWe used Western blot and immunohistochemical methods for investigating the content and distribution of calcineurin in the lung tissue. Calcineurin activity in different tissues was measured using (32)P-labelled substrate. In the primary culture of lung fibroblasts, (3)H-thymidine ((3)H-TdR) and (3)H-proline incorporation methods were used to study the effect of cyclosporin A (CsA), an inhibitor of calcineurin, on the lung fibroblast DNA and collagen synthesis stimulated by bFGF.

RESULTSWe found that calcineurin was expressed in lung tissue and has phosphatase activity (7.1 +/- 2.0 pmol Pi/mg pr/min). CsA (10(-8) - 10(-6) mol/L) inhibited lung fibroblast (3)H-TdR incorporation induced by bFGF in a dose-dependent manner, with the inhibitory rates by 20%, 46% and 66% (P < 0.01). CsA (10(-7) - 10(-6) mol/L) inhibited (3)H-proline incorporation in lung fibroblasts stimulated by bFGF, with the inhibitory rates by 21% and 37% (P < 0.01). In a culture medium, CsA (10(-8) - 10(-6) mol/L) inhibited (3)H-proline secretion induced by bFGF in a dose-dependent manner, with the inhibitory rates by 19%, 29% (P < 0.05) and 56% (P < 0.01). CsA (10(-7) mol/L) could inhibit calcineurin activity by 44% in lung fibroblasts (P < 0.01).

CONCLUSIONSCalcineurin is expressed in lung tissue and has phosphatase activity. It is involved in the bFGF stimulated lung fibroblast DNA and collagen synthesis.

Animals ; Calcineurin ; analysis ; physiology ; Cell Division ; Cell Survival ; drug effects ; Collagen ; biosynthesis ; Fibroblast Growth Factor 2 ; pharmacology ; Fibroblasts ; drug effects ; physiology ; Lung ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective: To determine the role of cross-talk between calcineurin-dependent signal transduction pathway and protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) in airway remodeling in asthma. Methods: Male guinea pigs were sensitized with intraperitoneal injections of ovabumin (OVA), then treated with cyclosporin A (CsA,5 mg/kg), an inhibitor of calcineurin, then inhaled OVA for 2 weeks 14 days later. Activities of calcineurin, PKC, MAPK, and PKA were was analyzed by phosphorylation and dephosphorylation. In primary cultures of rat airway smooth muscle cells (ASMC), activities of calcineurin, PKC, MAPK, and cross-talk induced by urotensin Ⅱ (UⅡ), a recently identified strong mitogen, were measured. Results: (1) The activities of calcineurin, MAPK and PKC increased by 19% (P0.05). (4) CsA 10 -6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P0.05). Conclusion:The signal transduction pathways between calcineurin and other protein kinases such as PKC, MAPK and PKA have cross-talk in airway remodeling in asthma.

Objective:To investigate the role of endogenous hydrogen sulfide(H2S)in patients with asthma.Methods:Levels of serum H2S,lung function and cell differential count in induced sputum were studied in 44 patients with acute exacerbation of asthma,33 patients with stable asthma and 12 health subjects.Of the 33 patients with stable asthma,3 failed to achieve induced sputum.Results:The serum H2S level was(75.2?13.0)?mol/L in controls(12 cases),(55.8?13.6)?mol/L in patients with stable asthma(33 cases),(57.8?6.3)?mol/L in patients with mild of acute exacerbation asthma(9 cases),(40.8?5.1)?mol/L in that with moderate of acute exacerbation asthma(13 cases),and(31.3?2.9)?mol/L in that with severe of acute exacerbation asthma(22 cases,F=44.592,P