幽门螺杆菌尿素酶B亚单位Th表位的免疫学特性研究

采用MHC限制性分析、ELISA方法、淋巴细胞增殖实验等方法研究幽门螺杆菌(Hp)尿素酶B亚单位(UreB)的H- 2~d限制性Th表位U_(546-561)、U_(229-244)、U_(237-251)的免疫学特性。发现抗I-E~d抗体能够抑制U_(546-561)对CD4~+T淋巴细胞的刺激,抗I-A~d抗体能够抑制U_(229-244)、U_(237-251)对CD4~+T淋巴细胞的刺激作用。U_(229-244)、U_(229-244)能刺激CD4~+T淋巴细胞分泌IL-4和IL-10,U_(237-251)刺激CD4~+T淋巴细胞分泌IFN-γ、IL-2,且U_(546-561)、U_(229-244)、U_(237-251)三个表位肽免疫BALB/c小鼠能够引起针对各自免疫多肽和rUreB的CD4~+T细胞应答。结果表明U_(546-561)为I-E~d限制性Th2表位,U_(229-244)为I-A~d限制性Th2表位、U_(237-251)为I-A~d限制性Th1表位。三个表位之间具有协同刺激效应,可以用于Hp表位疫苗的研究。     

Qiangli Wuhu mixture alleviates LPS-induced pneumonia by inhibiting the TLR4/NF-κB/NLRP3 pathway: a study based on network pharmacology

ContextQiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia.ObjectiveTo clarify the mechanisms of QLWH in treating pneumonia.Materials and methodsThe potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH.ResultsNine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1β (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice (p < 0.05).Discussion and conclusionsThis study combined network pharmacology and animal experiments, providing effective evidence for the clinical promotion of QLWH. Meanwhile, it is of significance for further development.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Utility of Direct Peroral Cholangioscopy Using a Multibending Ultraslim Endoscope for Difficult Common Bile Duct Stones

Background/AimsTreatment options for difficult bile duct stones are limited. Direct peroral cholangioscopy (POC)-guided lithotripsy may be an option. A newly developed multibending (MB) ultraslim endoscope has several structural features optimized for direct POC. We evaluated the utility of direct POC using an MB ultraslim endoscope for lithotripsy in patients with difficult bile duct stones.MethodsTwenty patients with difficult bile duct stones, in whom stone removal using conventional endoscopic methods, including mechanical lithotripsy, had failed were enrolled from March 2018 to August 2019. Direct POC-guided lithotripsy was performed by electrohydraulic lithotripsy or laser lithotripsy. The primary outcome was complete ductal clearance, defined as the retrieval of all bile duct stones after lithotripsy confirmed by balloon-occluded cholangiography and/or direct POC.ResultsThe technical success rate of direct POC was 100% (20/20), and the free-hand insertion rate was 95% (19/20). Direct POC-guided lithotripsy, attempted by electrohydraulic lithotripsy in nine patients (45%) and laser lithotripsy in 11 patients (55%), was successful in 95% (19/20) of the patients. Complete ductal clearance after direct POC-guided lithotripsy was achieved in 95% (19/20) of patients. Patients required a median of 2 (range, 1–3) endoscopic retrograde cholangiopancreatography sessions for complete stone removal. Adverse event was observed in one patient (5%) with hemobilia and was treated conservatively.ConclusionsDirect POC using an MB ultraslim endoscope was safe and effective for lithotripsy in patients with difficult bile duct stones.     

Experiment and Theoretical Investigation on Fatigue Life Prediction of Fracturing Pumpheads Based on a Novel Stress-Field Intensity Approach

Fracturing pumpheads are typical pressure vessels that experience frequent fatigue failure under the effect of notches in their cross-bore. To enhance the fatigue life of fracturing pumpheads, the study of the notch effect is indispensable and important to establish a reliable mathematical model to predict their fatigue life. In the present paper, two novel fatigue life prediction models are proposed for notched specimens. In these models, two new geometric fatigue failure regions are defined to improve the weight function. Finally, the elaborated novel stress-field intensity approach was applied to three different types of notched specimens. Experiment results indicate that the new SFI approach achieves 47.82%, 39.48%, and 31.85% higher prediction accuracy than the traditional SFI approach, respectively. It was found that the modified SFI approach provided better predictions than the traditional SFI approach and the TCD method. The II-th novel SFI approach had the highest accuracy, and the I-th novel SFI approach was more suitable for sharply notched specimens.     

Association Between Nap and Reported Cognitive Function and Role of Sleep Debt: A Population-Based Study

Background and PurposeThe relationship between napping and cognition remains controversial. This study aimed to investigate the association between napping and cognition according to sleep debt in the Korean adult population.MethodsA population-based nationwide cross-sectional survey was conducted in 2018. A two-stage stratified random sample of Koreans aged ≥19 years was selected and evaluated using questionnaires by trained interviewers. Cognitive function was assessed using the Mail-In Cognitive Function Screening Instrument (MCFSI). Sleep habits on weekdays and weekends, napping, and subjective sleep requirements were assessed using the questionnaires. Accumulated sleep debt was calculated by subtracting the weekly average sleep duration from subjective sleep requirements. Sleep quality, daytime sleepiness, insomnia, depression, demographics, and comorbidities were assessed. Participants were grouped into those with sleep debt ≤60 min and those with sleep debt >60 min. Multiple linear regression was used to estimate the independent association between the factors and cognition.ResultsIn total, 2,501 participants were included in the analysis. Naps were reported in 726 (29.0%) participants (nappers). The mean MCFSI score was higher in nappers (3.4±3.6) than in non-nappers (2.3±3.0) (p<0.001). Multiple linear regression controlling for age, alcohol, smoking, depression, insomnia, daytime sleepiness, sleep quality, and education revealed that 30 to 60 min of napping was associated with worse cognitive function in participants with sleep debts ≤60 min, while >60 min of napping was associated with better cognitive function in participants with sleep debts >60 min.ConclusionsIn general, naps are associated with worse cognitive function in the Korean adult population. However, for those with sleep debt of >60 min, naps for >60 min were associated with better cognitive function.     

联合检测对地中海贫血实验诊断的应用价值

目的 评价红细胞平均体积（MCV）、红细胞脆性试验和血红蛋白（Hb）电泳在地中海贫血诊断及其产前筛查中的价值。方法 选择2004年至2005年间在我院进行系统产前检查的已被基因诊断证实的210例地中海贫血夫妇的筛查实验结果进行回顾性分析。结果 MCV、红细胞脆性试验及Hb电泳单项检测在地中海贫血产前筛查的灵敏度和特异度分别为97．6％、89．5％、90．0％及76．0％、89．3％、97．3％;MCV与Hb电泳、红细胞脆性试验与Hb电泳2项平行联合检测的灵敏度及特异度分别为100．0％、86．7％及99．0％、89．3％,系列联合检测的灵敏度及特异度分别为89．0％、99．7％及87．1％、100．0％。MCV、红细胞脆性试验及Hb电泳3项平行联合检测的灵敏度及特异度分别为100．0％、79．7％;3项系列联合检测灵敏度及特异度为86．7％、100．0％。经u检验,平行联合检测的灵敏度与各单项检测灵敏度之间、系列联合检测的特异度与各单项检测特异度之间差异有统计学意义（P〈0．05）。结论 MCV、红细胞脆性试验及Hb电泳3项联合检测是地中海贫血诊断及其产前筛查中最理想的试验方法。     

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

Association between plasma Vitamin B5 levels and all‐cause mortality: A nested case‐control study

We aimed to evaluate the prospective association of vitamin B5 with all‐cause mortality and explore its potential modifiers in Chinese adults with hypertension. A nested, case‐control study was conducted in the China Stroke Primary Prevention Trial, including 505 deaths of all causes and 505 matched controls. The median follow‐up duration was 4.5 years. The primary outcome measure in this investigation was all‐cause mortality, which encompassed deaths for any reason. The mean plasma vitamin B5 concentration for cases (43.7 ng/mL) was higher than that in controls (40.9 ng/mL) (p = .001). When vitamin B5 was further assessed as quintiles, compared with the reference group (Q1: < 33.0 ng/mL), the risk of all‐cause mortality increased by 29% (OR = 1.29, 95% CI: 0.83‐2.01) in Q2, 22% (OR = 1.22, 95% CI: 0.77‐1.94) in Q3, 62% (OR = 1.62, 95% CI: 1.00‐2.62) in Q4, and 77% (OR = 1.77, 95% CI: 1.06‐2.95) in Q5. The trend test was significant (p = .022). When Q4‐Q5 were combined, a significant 41% increment (OR = 1.41, 95% CI: 1.03‐1.95) in all‐cause death risk was found compared with Q1‐Q3. The adverse effects were more pronounced in those with normal folate levels (p‐interaction = .019) and older people (p‐interaction = .037). This study suggests that higher baseline levels of plasma vitamin B5 are a risk factor for all‐cause mortality among Chinese patients with hypertension, especially among older adults and those with adequate folate levels. The findings, if confirmed, may inform novel clinical and nutritional guidelines and interventions to optimize vitamin B5 levels.     

Clinical course and outcomes of COVID-19 patients with chronic obstructive pulmonary disease: A retrospective observational study in Wuhan,China

Information about coronavirus disease 2019 (COVID-19) patients with pre-existing chronic obstructive pulmonary disease (COPD) is still lacking. The aim of this study is to describe the clinical course and the outcome of COVID-19 patients with comorbid COPD.This retrospective study was performed at Wuhan Huoshenshan Hospital in China. Patients with a clear diagnosis of COVID-19 who had comorbid COPD (N = 78) were identified. COVID-19 patients without COPD were randomly selected and matched by age and sex to those with COPD. Clinical data were analyzed and compared between the two groups. The composite outcome was the onset of intensive care unit admission, use of mechanical ventilation, or death during hospitalization. Multivariable Cox regression analyses controlling for comorbidities were performed to explore the relationship between comorbid COPD and clinical outcome of COVID-19.Compared to age- and sex-matched COVID-19 patients without pre-existing COPD, patients with pre-existing COPD were more likely to present with dyspnea, necessitate expectorants, sedatives, and mechanical ventilation, suggesting the existence of acute exacerbations of COPD (AECOPD). Greater proportions of patients with COPD developed respiratory failure and yielded poor clinical outcomes. However, laboratory tests did not show severer infection, over-activated inflammatory responses, and multi-organ injury in patients with COPD. Kaplan–Meier analyses showed patients with COPD exhibited longer viral clearance time in the respiratory tract. Multifactor regression analysis showed COPD was independently correlated with poor clinical outcomes.COVID-19 patients with pre-existing COPD are more vulnerable to AECOPD and subsequent respiratory failure, which is the main culprit for unfavorable clinical outcomes. However, COPD pathophysiology itself is not associated with over-activated inflammation status seen in severe COVID-19.