Objective To evaluate the dosage regimen of sulfasalzine combined with recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR) in the induction and maintenance of remission in active ankylosing spondylitis.Methods This study enrolled 100 ankylosing spondylitis patients with disease duration for less than five years who were treated with sulfasalzine and rhTNFR combination therapy.Patients were randomly assigned to three groups six weeks later:patients in the G1 group received sulfasalzine combined with rhTNFR at a 25 mg dosage twice each week.Patients shifted to monotherapy with sulfasalzine six weeks later:patients in G2 group received sulfasalzine combined with rhTNFR at 25 mg dosage per week.Patients were switched to monotherapy of sulfasalzine twelve weeks later:patients in G3 group received sulfasalzine combined with rhTNFR at 25 mg dosage once every ten days.Patients were changed to monotherapy of sulfasalzine seventeen weeks later.The whole treatment lasted for 24 weeks.All participants were followed up at week 0,6,12,18,24 respectively and were evaluated by BASDAI 50.The primary end-point of this study was the percentage of patients achieved BASDAI 50 remission.Data were analyzed with SPSS version 17.0.Independent t-test and x2 test were adopted to analyze data.Results 90％ of patients treated with combination therapy reached BASDAI50 at the 6th week.All patients in the G1 group achieved BASDAI 50 remission at 12th week,but the percentage dropped to 68.7％ at 18th week,which gradually decreased to 37.5％ at the 24th week.In G2 group,93.9％ patients reached BASDAI50,which declined to 81.8％ at the 18th week.The whole number accounted for 60％ at the end point of 24th week.In G3 group,85.7％ patients achieved BASDAI50 at the 12th week,accounted for 74.3％ at 18th week,and declined to 68.6％ at the 24th week.G3 group of patients presented a significantly higher rate than other groups(P＜0.05).Conclusion Sulfasalzine and rhTNFR combination therapy can gain remission in active AS patients after treated for six weeks.Doctors may extend TNF antagonist treatment in order to achieve long-term remission.

Objective:To develop and validate a predictive model for post-anesthesia care unit (PACU) hypotension in elderly patients undergoing painless gastrointestinal endoscopy.Methods:The medical records of elderly patients of both sexes, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing painless gastrointestinal endoscopy at the Endoscopy Center of Subei People′s Hospital from March to June 2021, were retrospectively collected. The patients were randomly divided into training and validation sets according to the ratio of 3∶1. In the training set, the characteristic variables associated with PACU hypotension were screened by Lasso regression, and the independent risk factors for PACU hypotension were identified by multivariate logistic regression analysis of the characteristic variables, according to which a nomogram model predicting the risk for PACU hypotension was established.The discrimination, calibration and accuracy of the model were evaluated by calibration curve and receiver operating characteristic(ROC)curve. And the clinical practicability of the model was determined by decision curve analysis and further assessed by external validation.Results:Of the 973 patients ultimately included, 378 patients experienced PACU hypotension, with an incidence of 38.8%. Multivariate logistic regression analysis showed that age, prolonged preoperative water deprivation time, increased percentage of changes in SBP before and after induction, and intraoperative MAP <65 mmHg were independent risk factors for hypotension in the PACU, and intraoperative use of norepinephrine was a protective factor. The nomogram model was then developed based on the results. The area under the ROC curve was 0.710 (95% confidence interval [ CI] 0.672-0.748) in training set and 0.778 (95% CI 0.720-0.837) in validation set. In training and validation sets, the calibration curves were tested by Hosmer-Lemeshow good of fit test, the P values were 0.590 and 0.950, respectively. The decision curve analysis curve showed that the risk threshold of the prediction model in the training and validation sets were between 20% and 82% and between 18% and 92%, respectively, in the external validation. Conclusions:The nomogram model for prediction of PACU hypotension is successfully established based on age, prolonged preoperative water deprivation, percentage of change in SBP before and after induction, intraoperative MAP <65 mmHg and use of norepinephrine in elderly patients undergoing painless gastrointestinal endoscopy, and the model can visually and individually predict the risk of PACU hypotension.

Adolescent ; Child ; Child, Preschool ; Female ; Hematologic Neoplasms ; complications ; Humans ; Infant ; Lung Diseases, Fungal ; drug therapy ; etiology ; Male

Objective:To investigate the mechanism of excessive inflammation in the lung of C3H/HeN(C3H) mice following Chlamydia muridarum(Cm) airway infection.Methods:Chlamydial pneumonitis was induced in C3H and C57BL/6(C57) mice by intranasal inoculation with 1×103IFU (inclusion forming unites) of Cm strains.The expression of TLR2,TLR4 and MyD88 mRNA in the lung at different time point post-infection was measured by RT-PCR.Results:Cm infection induced Toll-like receptors expression in two strains of mice.The expression of TLR2 and TLR4 mRNA,especially TLR2 mRNA(P<0.001 or P<0.05),were significantly higher in highly susceptible C3H mice on day 7 and day 14 d post-infection compared with C57 mice.Further studies showed that the expression of MyD88 mRNA was also significantly higher in C3H mice on day 7 post-infection,and maintained high expression untill the day 14.Conclusion:Cm lung infection induced high level of TLR2,TLR4 and MyD88 mRNA expression in C3H mice,which may associate with excessive inflammation in C3H mice.

This study was purposed to explore the changes of possible angiogenetic factors other than VEGF after inhibition of NHE1 and their related mechanisms. The K562 cells were treated by NHE1 specific inhibitor cariporide, the angiogenesis factors after inhibition of NHE1 were screened by using protein chip, the IL-8 expression level after cariporide treatment was detected by real-time quantitative PCR; the K562 cells with stable interference of NHE1 were constructed, the IL-8 expression level after interference of NHE1 was detected by real-time quantitative PCR; the p38 phosphorylation level in K562 cells treated with cariporide was detected by Western blot. After treatment of K562 cells with p38 inhibitor SB203580, the IL-8 expression level was decreased by real-time quantitative PCR. The results of protein chip showed that IL-8 expression decreased after cariporide treatment. Real-time quantitative PCR confirmed this inhibitory effect. The p38 phosphorylation level increased after cariporide treatment. The down-regulation of IL-8 expression induced by cariporide treatment was partially restored after K562 cells were treated with p38 inhibitor SB203580. It is concluded that the inhibition of NHE1 can inhibit IL-8 expression through up-regulation of p38 phosphorylation.
Cation Transport Proteins ; antagonists & inhibitors ; Down-Regulation ; Guanidines ; pharmacology ; Humans ; Imidazoles ; pharmacology ; Interleukin-8 ; metabolism ; K562 Cells ; Phosphorylation ; drug effects ; Pyridines ; pharmacology ; Sodium-Hydrogen Exchanger 1 ; Sodium-Hydrogen Exchangers ; antagonists & inhibitors ; Sulfones ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis