Objective To study the effects of ulinastatin on proinflammatory cytokine and oxygen free radicals during acute lung injury in rabbits. Methods Eighteen health New Zealand rabbits were randomly divided into 2 groups: oleic acid group(n=9) and ulinastatin group(n=9). The rabbits of oleic acid group were intravenously injected analytical pure oleic acid(0.12ml/kg) to set up a model of acute lung injury. The rabbits of ulinastatin group were intravenously injected ulinastatin 50000u/kg before injecting oleic acid and received intravenous infusion of ulinastatin 5000u?kg -1 ?h -1 after injecting oleic acid. Before injecting oleic acid and 1h, 2h, 3h and 4h after injecting oleic acid,venous blood samples were taken to determine the concentration of plasma IL-8, MDA and active oxygen,and arterial blood samples were also taken for gas analysis. Results The concentration of IL-8, MDA and active oxygen and PaCO 2 gradually increased,and PaO 2 gradually decreased after injecting oleic acid in the both groups of rabbits. The changes of the above indices in the oleic acid group were larger than those in the ulinastatin group, and the difference between the two groups was significant. Conclusion Ulinastatin inhibited the release of proinflammatory cytokine and reduced the production of oxygen free radicals during acute lung injury.

Objective It has been shown that ketamine can effectively suppress expression of cell adhesion molecules in vitro. The purpose of this study was to investigate the effect of ketamine on plasma adhesion molecules in vivo during cardiac valve replacement.Methods Twenty ASA Ⅲ-Ⅳ patients (7 males, 13 females) aged 23-65 yrs, weighing 31-77 kg undergoing cardiac valve replacement were randomly divided into two groups of 10 patients each : ketamine group received ketamine 2 mg?kg-1 i.v. before induction of anesthesia and at the start of CPB and control group received normal saline instead of ketamine. Blood samples were taken from radial artery for determination of plasma P-selectin, L-selectin, ICAM-1, IL-6 and cTnI concentrations before induction of anesthesia (T0 ,baseline) , 20 min after initiation of CPB (T1) , 30 min after aortic declamping (T2) 4 h and 24 h after CPB (T3, T4) . Results There was no significant difference between the two groups in age, weight, operation time, CPB time and aortic cross-clamping time. The concentrations of P-selectin, L-selectin, ICAM-1 and IL-6 at T1-4 and cTnI at T2-4 increased significantly compared to baseline (T0) in both groups ( P

OBJECTIVE: To explore the effect of isoflurane preconditioning on the plasma concentration of matrix metalloproteinase (MMP)-9 and myocardial ultramicrostructure in patients undergoing cardiac valve replacement. METHODS: Thirty patients undergoing elective cardiac valve replacement with cardiopulmonary bypass (CPB) were randomly assigned to a control group (ný15) and an isoflurane group (ný15). In the isoflurane group, isoflurane of 1.0 minimum alveolar concentration end-tidal( 1.1% approximately 1.2%) was administered for 30 min followed by a 15 min washout period before the CPB. The control group did not inhale isofurane, and there was no difference in the other drugs in the 2 groups. Blood samples for MMP-9 were obtained before incision(T(0)) and at 30 min (T(1)),6 h (T(2)),12 h (T(3)), and 24 h (T(4)) after the reperfusion. Right atrial biopsies were collected before and after the CPB to observe the myocardial ultramicrostructure. RESULTS: Compared with T(0), the mean MMP-9 level significantly increased at T(1), T(2) and T(3) in the control group(P<0.01), while the MMP-9 level only at T(1) significantly increased in the isoflurane group (P<0.01). The mean MMP-9 level was significantly reduced in the isoflurane group at T(2) compared with each time point in the control group. The difference in MMP-9 levels between T(1), T(2), T(3) and T(0) was significantly lower in the isoflurane group than that in the control group (P<0.01). The ultramicrostructure injury of myocardium under electron microscope in the control group was worse than that in the isoflurane group. CONCLUSION The plasma concentration of MMP-9 is inhibited by isoflurane preconditioning in patients undergoing cardiac valve replacement after CPB, which might be part of its protective mechanism against myocardium injury after CPB.
Adolescent ; Adult ; Cardiopulmonary Bypass ; Cardiotonic Agents ; therapeutic use ; Female ; Heart Valve Prosthesis Implantation ; methods ; Humans ; Ischemic Preconditioning, Myocardial ; methods ; Isoflurane ; therapeutic use ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Myocardium ; ultrastructure ; Young Adult

OBJECTIVE: To elucidate the effects of mammalian sterile 20-like kinase 1 (MST1) gene on tumor necrosis factor (TNF)-α-mediated human umbilical vein endothelial cell (HUVEC) apoptosis. METHODS: Cultured HUVECs were treated with either vehicle or TNF-α (1-100 ng/mL) for 24 hours. Cell apoptosis was measured by TUNEL staining, and MST1 activity was analyzed by Western blot. In order to knock down MST1 expression in HUVECs, cells were transfected with 100 nmol/L MST1 small interference RNA (siRNA) using Lipofectamine 2000 for 24 hours, and the transfection efficiency was analyzed by Western blot. MST1 siRNA-transfected cells were treated with 10 ng/mL TNF-α for an additional 24 hours. Cell apoptosis was measured by TUNEL staining and caspase-3 activity was detected by Western blot. RESULTS: MST1 activity was stimulated in a dose-dependent manner after TNF-α treatment (10, 40, 100 ng/mL) and reached the maximal effect at 100 ng/mL. MST1 activity also paralleled the onset of apoptosis as determined by TUNEL staining (P<0.001). Transfection with MST1 siRNA markedly diminished MST1 gene expression in a dose-dependent manner. MST1 siRNA (100 nmol/L) significantly silenced MST1 gene (P<0.05) and reduced TNF-α-induced endothelial cells apoptosis (P<0.05) by way of inhibiting MST1 gene activation and, accordingly, suppressing caspase-3 activity. CONCLUSION Silencing of MST1 expression by siRNA diminishes TNF-α-mediated human umbilical vein endothelial cell apoptosis by inhibiting the cascade effect of caspase-3.
Apoptosis ; genetics ; Cells, Cultured ; Hepatocyte Growth Factor ; genetics ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Proto-Oncogene Proteins ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Tumor Necrosis Factor-alpha ; pharmacology

Objective: To analyze the clinical data of children with rheumatic diseases complicated with osteonecrosis and summarize the clinical characteristics, so as to guide clinical work. Methods: The clinical data of 59 children with rheumatic diseases complicated with osteonecrosis from January 2010 to July 2018 were collected and analyzed retrospectively. Results: Among 59 children with rheumatic diseases complicated with bone infarction, 25 cases were systemic lupus erythematosus (SLE), 4 cases were mixed connective tissue disease, 6 cases were juvenile dermatomyositis, 1 case was Takayasu arteritis, 1 case was leukocy to clystic vasculitis, 13 cases were systemic onset juvenile idiopathic arthritis (SJIA), 1 case was polyarthritis, and 8 cases were juvenile ankylosing spondylitis. The median time from the onset of rheumatic diseases to osteonecrosis onset was 18 (7.00, 38.75) months. A total of 115 joints were involved in 59 children, the most common of which were bilateral hips and knees. Twenty-five were single joint involvement and 34 were multiple joints involvement. There were 37 cases (63%) with vasculitis, 9 cases (15%) with oralulcer, 5 cases (8%) with Raynaud's phenomenon, 31 cases (53%) with Cushing's face, 18 cases (31%) with kidney involvement, 25 cases (42%) with hypertension, and 12 cases (24%) with spinal compression frac- tures. According to statistics, 10 children with osteonecrosis occurred without glucocorticoid intake. The longest duration of glucocorticoid therapy was 13 years, and the average duration was about (27±35) months whensymptomatic osteonecrosis occurred. The median cumulative dose of prednisone was 381.9(209.77, 561.19) mg/kg. Conclusion SLE, SJIA and juvenile ankylosing spondylitis are the three most common rheumatic diseases in children with osteonecrosis. The locations of osteonecrosis are mostly the bilateral hips and knees. It is necessary to strengthen joint examination, physical examination and imaging screening for children with rheumatic diseases after 18 months of onset, so early detection, early treatment are the strategy to improve the prognosis of the diseases.

Objective? To explore the effect of video education combined with Teach-back on the compliance of patients with rheumatoid arthritis(RA) to exercise at home and the condition of disease activity. Methods? By convenience sampling, 80 patients with RA who were hospitalized in the Rheumatology and Immunology Department of Sichuan Provincial People's Hospital from March to November 2018 were included in the study. By random number table, the patients were divided into the intervention group and control group, the control group was given routine discharge instruction and the patients were taught about the functional exercise orally; on the basis of that, the intervention group was given the video education combined with Teach-back and assisted to download videos, Family Exercise Compliance Scale and Disease Activity Score in 28 Joints(DAS28) were used to evaluate the patients' compliance in functional exercise at home and disease activity condition before intervention, 1 month and 3 months after intervention. Results? Finally, 73 cases(37 cases in the control group, 36 cases in the intervention group) in two groups completed the research plan. One and 3 months after intervention, the compliance with family functional exercise of the intervention group was better than the control group from the same period with statistical significance(P＜0.05); the scores of Tender Joint Coun(t TJC28), Swollen Joint Coun(t SJC28), Patient General Health(GH) of the intervention group were all lower than the control group from the same period with statistical significance (P＜0.05), however, the scores of Erythrocyte Sedimentation Rate(ESR) and DAS28 didn't demonstrate obvious intervention effects (P＞0.05). Conclusions? Video education combined with Teach-back can effectively improve the compliance of RA patients with home functional exercise, help to cultivate healthy behavior, and hence reduce the number of tender joint, swelling joints, reduce the degree of pain, improve the prognosis of patients.

Objective:To explore the clinical characteristic and prognosis of juvenile dermatomyositis (JDM) by retrospectively study of the clinical manifestations, laboratory examinations, treatment and follow-up results. The aim of this study was to improve the diagnosis and treatment of JDM and reduce the complications and mortality.Methods:Medical charts of 612 JDM cases hospitalized to Beijing children's hospital from July 2002 to July 2018. We retrospectively analyze the onset, clinical manifestations, laboratory examinations, treatment and the follow-up, and then summarize the clinical characteristics and assess the therapeutic effect and prognosis.Results:There were 278 male and 334 female. The maleto female ratio was 1∶1.2. Themedian age at symptoms onset was 5.4(2.9-8.4) years old (range 6 months to 14 years). Rash was the most common initial presentation. The main clinical manifestations were rash (100%, 612 cases) and muscles weakness (96.1%, 588 cases). The most commonly involved organs by JDM were lung (57.5%, 352 cases), digestive tract (38.5%, 236 cases) and heart (32.5%, 199 cases). Muscle enzymes elevated in 95.5% (584 cases) of the patients and 89.5%(534 cases) of the patients had typical changes on electromyography. Muscle biopsy was performed in 134 patients and pathologicresults were compatible with JDM. For the treatment, all of the patients were treated by steroids plus therapy combined with immunosuppressive agents. Mostof the patients got good effect and outcome. Twenty-four patients died, and acute respiratory failurewas the most common cause of death. 17.9%(105 cases) of patients had complications. The complications included calcinosis in 70 patients and amyotrophy in 35 patients.Conclusion:JDM is a rare disease of children, andis characterized by muscle weaknessand rash. Severe organ involvement may cause death. Treatments include corticosteroids and immunosuppressive agents, andthe outcome is generally good.

Objective:To compare the disease outcome, quality of life score [evaluated by child health assessment questionnaire - disability index(CHAQ-DI)] and medical expenses of children with systemic juvenile idiopathic (sJIA) combined with macrophage activation syndrome (MAS) diagnosed by two different criteria.And to analyze the impacts of early MAS diagnosis criteria on the prognosis of sJIA combined with MAS in children.Methods:From January 2016 to December 2020, children with high disease activity of sJIA who were diagnosed and initially treated in the Department of Rheumatology of Beijing Children′s Hospital were enrolled in this study.Clinical characteristics on admission were recorded as baselines.Patients were divided into 2 groups according to different diagnostic criteria.Children diagnosed as MAS based on the 2016 The European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation MAS diagnostic criteria were included in MAS control group(38 cases), and those diagnosed as early MAS based on the sJIA combined MAS early warning scale but did not meet the 2016 diagnostic criteria were included in MAS early warning group(38 cases). Basic information, clinical manifestations and laboratory test results were collected.According to the clinical manifestations and laboratory results in different periods of follow-up at 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months after treatments, the di-sease activity, CHAQ-DI and medical expenses were compared between the two groups.Results:There were no signi-ficant differences in the disease activity, duration of sJIA and medical expenses between the two groups (all P>0.05). In terms of laboratory results, serum ferritin in MAS early warning group were significantly lower than that of MAS control group at 4 weeks after treatment[(333.97±186.66) μg/L vs.(389.66±221.76) μg/L]( t=-83.47, P<0.05). In terms of disease activity, after 12 months of treatment, the evaluation of American College of Rheumatology pediatric indexes 70 in MAS early warning group was better than that in MAS control group [34.2%(13/38 cases) vs.7.9% (3/38 cases)]( χ2=6.067, P<0.05). In terms of CHAQ-DI, at 4 weeks, 8 weeks, 12 weeks and 6 months of treatment, CHAQ-DI in MAS early warning group were better than those in MAS control group, and the difference were statistically significant ( t=-0.34, -0.27, -0.23, -0.09; all P<0.05). In terms of cumulative medical expenditure at 12 months of treatment, the MAS early warning group was lower than the MAS control group [(114.3±80.7) thousand yuan vs.(157.9±111.7) thousand yuan]( t=-3.97, P<0.05). Conclusions:Quickly judge the condition through the quantitative integral of clinical examination and test indexes, screening and treatment of MAS in early stage are helpful to improve the prognosis and reduce the medical consumption.

Objective:To analyze the outcome of 15 cases with refractory systemic lupus erythematosus (SLE) treated with Belimumab, and evaluate the safety and efficacy of the therapy.Methods:A retrospective and real-world clinical research method was adopted.Fifteen children with confirmed refractory SLE and complete follow-up data were selected from the Department of Rheumatology, Beijing Children′s Hospital from April 1, 2020 to March 31, 2022.By comparing the changes of clinical symptoms, auxiliary examination results, SLE disease activity index (SLEDAI-2000) and Physician′s Global Assessment (PGA) scores as well as adverse events in different treatment periods (before treatment, 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months after treatment), the safety and effectiveness of Belimumab treatment were all recorded.The counting data was expressed in percentage, the measurement data meeting the normal distribution was expressed in Mean±SD, and the two samples of measurement data were compared by t-test, P<0.05 means significant differences. Results:The ratio of male to female was 3∶2, and the onset age was (7.93±4.99) years; The basic treatment time was 4 months to 5 years and 1 month.There were 8 cases with lupus nephritis (LN), 2 cases suffering from hypocomplementemia for more than 1 year, 2 cases with central nervous system involvements, 2 cases complicated with antiphospholipid syndrome and 1 case with early-onset SLE.Of 8 LN cases, 1 case was complicated with neuropsychiatric lupus (NPLE) and distal femoral head infarction of both knees, and 3 cases were complicated with lumbar compression fractures and hip infarction.All patients were treated with regular traditional therapy to induce remission.During the maintenance period, the disease activity maintained at light to moderate levels, and it was difficult to reduce glucocorticoid.At baseline, SLEDAI-2000 score was 4-13, and PGA score was 1-2.50.Basic treatment includes glucocorticoids combined with immunosuppressants (Cyclosporine, Mycophenolate Mofetil, Leflunomide tablets) and antimalarial drugs, and Cyclophosphamide and/or Tripterygium Wilfordii were used at the same time according to the damage of target organs.The drug safety after intravenous injection of Belizumab showed that one patient in this group had respiratory tract infection symptoms 4 weeks after treatment; Another patient had a slight increase of alanine aminotransferase 8 weeks after treatment, and recovered to normal symptomatic treatment.No drug-related adverse reactions were found in the other 13 patients.After 4 weeks of treatment, the score of SLEDAI-2000 and PGA compared with the baseline level, and the difference was statistically significant (SLEDAI-2000 P=0.002; PGA P=0.006). There was no clinical recurrence.One patient with familial chilblain like lupus erythematosus showed significant improvement in rash 2 weeks after treatment, and low fever accompanied by increased rash 8 weeks after treatment; After 16 weeks of treatment, the body temperature was normal and the rash basically subsided. Conclusions:Belimumab is clinically effective in the treatment of refractory childhood SLE, with no serious adverse events reported.However, its long-term efficacy and safety need to be further studied by multi-center and long-term research with a large sample size.

Objective To explore the gene mutation,clinical phenotype,treatment and prognosis of chronic infantile neurologic,cutaneous,articular (CINCA) syndrome,so as to improve the diagnosis rate,reduce the disability rate and teratogenicity rate of CINCA syndrome.Methods Ten children with CINCA syndrome admitted to our hospital were retrospectively analyzed in terms of the clinical phenotypes,auxiliary examinations,treatment and follow-up.Three ml ethylene diamine tetraacetic acid (EDTA) anticoagul-ation was taken from children and their parents with the consents.Genomic DNA was extracted by QIAamp whole blood Deoxynbonucleic acid (DNA) extraction kit (German Qiagen Company).The whole exons were detected by Agilent liquid phase capture technology (Agilent Company).Finally,Sanger sequencing was used to verify the results.Results In this study,eight mutations of NLRP3 gene were found in children with CINCA syndrome,namely 913G/A (D305N),1057G/T(V353L),1702T/A (F568I),1703T/A (F568Y),1710G/C (K570N),1789A/G (S597G),1991T/C (M664T),2269G/A (G757R).The onset age of most of the cases was less than half a month,and the initial manifestation was mainly urticaria-like rash.Short stature and special face could be seen in all 10 cases.All the patients had fever and urticarial rash in varying degrees during the course of the disease.Nine of them had obvious arthritis.Nine children had central nervous system involvement.There were 8 cases of binaural nervous deafness,7 cases of binocular optic neuritis,and 6 cases of hepato-splenomegaly and/or lymphadenopathy.Amyloid A was significantly increased.Glucocorticoids and immunosup-pressive agents are the basic drugs for the treatment of this disease.If the curative effect was not good,biological agents should be added early to alleviate the disease.Conclusion CINCA syndrome is a rare autosomal dominant hereditary disease,the main clinical manifestations of which are skin,joint and central nervous system involvement,and even amyloidosis of organs.Early diagnosis and active treatment can reduce the involvement of important organs.