随着铜绿假单胞菌（铜绿）的耐药性逐年增强，铜绿感染已经成为公共医疗卫生的重点关注问题。线粒体自噬及其介导的线粒体功能障碍在多种细菌感染中已被报道，但线粒体功能障碍在宿主调控铜绿感染中的作用尚不明确。因此，本研究建立铜绿刺激小鼠巨噬细胞感染模型和小鼠急性铜绿感染模型，探讨铜绿是否通过诱导线粒体自噬改变线粒体功能，进而影响宿主免疫炎症反应和细胞毒性，并通过监测生存率和肺组织病理学变化进一步确定线粒体自噬在小鼠铜绿体内感染模型中的作用。结果表明，铜绿引起小鼠腹腔巨噬细胞线粒体功能障碍，并通过线粒体自噬途径清除铜绿刺激引起的活性氧（ROS）累积，从而抑制铜绿引起的促炎性细胞因子分泌并增强细胞毒性。体内实验进一步确认线粒体自噬在铜绿体内感染中的作用。
Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Pseudomonas aeruginosa ; Macrophages/metabolism* ; Mitochondria ; Cytokines/metabolism*

Objective:To quantify any correlation between the severity of spinal curvature of an adolescent with idiopathic scoliosis and their cardiopulmonary exercise endurance.Methods:The cardiopulmonary exercise test (CPET) results and the full-length spinal X-rays in a standing position of 64 adolescents with idiopathic scoliosis were reviewed retrospectively. Independent t-tests were used to compare the two datasets obtained from those with left or right thoracic scoliosis. The correlation between the Cobb angle and cardiopulmonary exercise endurance was analyzed using Pearson correlation coefficients, multiple factor linear regression and two-stage linear regression.Results:After adjusting for gender, age, height and weight, the multiple linear regression analysis showed that the Cobb angle was significantly negatively correlated with maximum tidal volume (β=-0.013) and significantly positively correlated with the rate of respiration (β=0.421). The relationship between the Cobb angle and cardiopulmonary exercise endurance was non-linear. With a Cobb angle > 34°, a 1° increase reduces cardiopulmonary exercise endurance by a factor of 1.4 on average. At smaller Cobb angles the corresponding increase is about 0.87 times.Conclusions:The Cobb angle is a negative predictor of ventilation during exercise among adolescents with idiopathic scoliosis. The more severe a patient′s spinal curvature, the lower the cardiopulmonary exercise endurance is likely to be.

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.

Objective:To explore the efficacy and safety of intermittent infusion of ilaprazole sodium and high-dose continuous infusion of esomeprazole sodium in preventing rebleeding in patients with peptic ulcer bleeding after successful endoscopic hemostasis.Methods:This is a multi-center, interval randomized, double-blind, double-dummy, parallel controlled study. From March 3rd to June 15th, 2021, 151 patients with high risk of peptic ulcer bleeding and successfully underwent endoscopic hemostasis from 33 hospitals including the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Patients were interval randomly divided into the trial group (74 cases) and the control group (77 cases). Patients in the trial group received intermittent intravenous infusion of ilaprazole sodium once daily (20 mg administered as a 60 min intravenous infusion on day 1, and 10 mg administered as a 30 min intravenous infusion on day 2 and 3); patients in the control group received continuous intravenous infusion of esomeprazole sodium for 72 h (esomeprazole sodium 80 mg at first dose in half an hour, and 8 mg per hour continuous intravenous infusion for 71.5 h). After intravenous infusion treatment, patients of both groups were given oral ilaprazole enteric-coated tablets, 10 mg each time, once a day for 4 d. The rebleeding rate after 72 h and within 7 d after treatment and the proportion of patients who received endoscopic retreatment or surgery due to rebleeding within 72 h after treatment were analysised based on the full analysis set (72 cases in the trial group and 75 cases in the control group); and the incidence rate of adverse reactions was observed in the two groups based on the safety analysis set (74 cases in the trial group and 76 cases in the control group). Chi-square test or Fisher exact probability test was used for statistical analysis.Results:There was no rebleeding case in the trial group within 72 h and 1 case of rebleeding within 7 d (1.39%, 1/72). In the control group, there was 1 case of rebleeding (1.33%, 1/75) within 72 h and 4 cases of rebleeding (5.33%, 4/75) within 7 d. There was no significant difference in rebleeding rate either after 72 h or within 7 d after treatment between the two groups (both P>0.05). Within 72 h of treatment, no patients in both groups needed endoscopic or surgical retreatment due to rebleeding. Adverse reactions occurred in 5 cases (6.8%, 5/74) and 6 cases (7.9%, 6/76) in the trial group and control group, respectively, which recovered spontaneously without treatment. No serious adverse reactions occurred in both groups. Conclusion:In patients with high-risk peptic ulcer bleeding with successful endoscopic hemostasis, intermittent intravenous infusion of ilaprazole sodium has similar efficacy and safety as continuous high-dose intravenous infusion of esomeprazole sodium, but the dosage of intermitten regimen is less, the administration is more convenient, and it is worthy of clinical promotion.

Objective: To analyze the association between polycyclic aromatic hydrocarbons(PAHs)exposure and rheumatoid arthritis(RA)based on large sample data. Methods: The RA patients(RA group)and non-RA patients(non-RA group)with complete data were selected from the National Health and Nutrition Survey Database in the United States(NHANES)(2005—2014). The logistic regression model was used to analyze the association between 8 monohydroxylated(OH-)PAH metabolites in the urine and RA. Results: A total of 357 RA patients and 5, 256 non-RA participants were included.After adjusting the confounding factors by logistic analysis, the level of OH-PAHs mixture at the highest quartile(Q4)was associated with increased risk of RA compared with that at the lowest quartile(Q1)(OR=1.60, 95%CI: 1.16-2.23). For a single kind of OH-PAHs, the Q4 levels of 1-hydroxynaphthalene(OR=1.59, 95%CI: 1.14-2.23), 2-hydroxynaphthalene(OR=1.66, 95%CI: 1.19-2.32), 2-hydroxyfluorene(OR=1.61, 95%CI: 1.17-2.22), 3-hydroxyfluorene(OR=1.64, 95%CI: 1.18-2.27)and 1-hydroxyphenanthrene(OR=1.38, 95%CI: 1.00-1.94)were all associated with significantly increased risk of RA compared with the Q1 level(all P<0.05). However, the Q2 level of 1-hydroxypyrene(OR=0.60, 95%CI: 0.43-0.83)was related to a decreased incidence of RA(P<0.01). Conclusions OH-PAHs mixed exposure is a risk factor for RA.The association between the level of individual OH-PAH and the rate of RA is bidirectional and is depended on the type and concentration of OH-PAHs.

Objective:To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country.Methods:Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it′s disease status and risk factors.Results:(1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575).Conclusions:The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.

Objective: To explore the prognosis and risk factors of pyelectasis in high-risk infants. Methods: This was a retrospective study. Totally 960 high-risk infants, who accepted type B ultrasonic examination for fetus at 28th week of gestation and for newborns in 48 hours after birth, were included in the study in departments of obstetrics and eonatology, Shunyi Maternal and Children's Hospital of Beijing Children's Hospital during May 2012 to April 2013. The degree of pyelectasis was classified using Grignon grade and the paients were followed up for 3 years. The factors of epidemiology, high risk pregnant women, fetus and high-risk newborns that relate to pyelectasis were summarized. High-risk factors were analyzed by using logistic multivariate regression analysis. Results: Of 960 high-risk infants, 103 had abnormal urinary ultrasound results, 87 (9.1% of high-risk infants) were diagnosed with pyelectasis, 16 (1.7% of high-risk infants) were diagnosed with congenital anomalies of the kidney and urinary tract. According to the degree of pyelectasis, 68 infants were Grignon grade Ⅰ, male:female ratio=5.8∶1, left side:right side ratio=1.91∶1; 19 infants were Grignon grade Ⅱ, male:female ratio=5.33∶1, left side:right side ratio=2.12∶1. Postnatal follow-up results showed that pyelectasis disappeared in 48 cases (55% of pyelectasis cae), 40 infants were Grignon grade Ⅰ (59% of all Grignon grade Ⅰ patients), 8 infants were Grignon grade Ⅱ (42% of all Grignon grade Ⅱ patients); The result of risk factors analysis showed that the risk of pyelectasis in males was 4.368 times that of females (95%CI: 2.33-8.189, P<0.05); the risk of pyelectasis in low birth weight infants was 22.434 times that of non low birth weight infants (95% CI: 5.883-85.547, P<0.05). Conclusion The incidence of pyelectasis in high-risk infants was 9.1%. The mitigation rate of pyelectasis in Grignon grade Ⅰ to Ⅱ in fetal or newborn period is high. Patients in Grignon grade Ⅲ and above in fetal or new born period had high risk of congenital anomalies of the kidney and urinary tract. The risk of pyelectasis of male was higher than that of female; the risk of pyelectasis of low birth weight infant was higher than appropriate for gestational age infants.

Objective To investigate the levels of antibody to pertussis toxin (PT) IgG in newborns in Shunyi Women and Children's Hospital of Beijing Children's Hospital in 2016.Methods A total of 419 newborns were enrolled in this study.Umbilical cord blood sample was collected from each subject and detected by enzyme-linked immunosorbent assay to measure the concentration of PT-IgG.Besides,all newborns were followed up to January 31,2017.Chi-square test was used for statistical analysis.Results The detectable rate of umbilical cord blood samples for PT-IgG accounted for 30.1％ (126/419).The median antibody level was ＜ 5 U/ml,and the 90th and the 95th percentile were 14.3 and 24.0 U/ml,respectively.No cases of pertussis occurred at the end of follow-up.Conclusions The newborns born in Shunyi Women and Children's Hospital of Beijing Children's Hospital are generally lack of protective PT antibody.

Objective To investigate the predictive value of the whole nodule size and solid component size of lung adenocarcinoma manifesting as subsolid nodule(SSN) in three different dimensions for pathologic grade.Methods We evaluated retrospectively preoperative chest HRCT data of 125 patients with 127 SSNs surgically resected and pathologically conformed lung adenocarcinomas.All specimens were divided into two groups: a total of 69 SSNs in group A, including 22 AIS and 47 MIA;a total of 58 SSNs in group B, only including IAC.Computer aided diagnosis software were used to measure the one dimension maximum diameter of solid component with lung window setting(1D-SCLW),two dimension maximum diameter of solid component with lung window setting(2D-SCLW),one dimension maximum diameter of solid component with mediastinal window setting(1D-SCMW),two dimension maximum diameter of solid component with mediastinal window setting(2D-SCMW),one dimension maximum diameter of whole nodule with lung window setting (1D-WNLW), two dimension maximum diameter of whole nodule with lung window setting (2D-WNLW), and volume of solid component with threshold of-300 HU (SCT) of all SSNs.Results 1D-SCLW, 2D-SCLW,1D-SCMW,2D-SCMW,1D-WNLW,2D-WNLW and SCT of the group B were significantly larger than those of the group A(P=0.000).ROC analyses indicated that the diagnostic efficiency of SCT for the pathologic grade was the highest among 7 CT features(AUC=0.887, sensitivity:81%,specificity:93%);The cut-off values of 1D-SCLW,2D-SCLW,1D-SCMW,2D-SCMW,1D-WNLW, 2D-WNLW and SCT were 17.50 mm,14.75 mm,9.50 mm,7.75 mm,0.50 mm,1.25 mm and 139.00 mm3.Multiple Logistic regression analysis revealed that SCT was the independent predictor of pathologic grade(OR=4.978,95%CI=1.430-17.331,P=0.012).SCT of 139.00 mm3 or greater was a significant indicator of IAC.Conclusion Among the whole nodule size and solid component size of SSN in three different dimensions on preoperative HRCT, SCT is found to be the independent predictor of pathologic grade, which may provide reference for surgery.

Objective To analyze the correlation between emphysema extent measured by high resolution computed tomography (HRCT) and pulmonary function tests, symptom score in patients with chronic obstructive pulmonary disease ( COPD ) , and to study the value of HRCT in the emphysema quantification in the clinical evaluation of COPD patients. Methods 78 patients with stable COPD were recruited to take the HRCT scan , and emphysema extent was qualified by measuring the proportion of low attenuation area in the whole lung (LAA%). Correlations between LAA% and indices of pulmonary function test, bronchial dilation test, mMRC scale, CAT score and six minutes walking distance (6MWD) were assessed. Results LAA% was negatively correlated with FEV1/FVC and DLCO%pred, and the correlation coefficients were -0.759 and -0.589 (P <0.01), respectively. LAA% was positively related to mMRC score (r = 0.342, P < 0.01), and negatively asso-ciated with 6MWD (r = -0.365,P< 0.01). There was no association between LAA% and indices of bronchodila-tion test (⊿FVC, ⊿FVC%, ⊿FEV1, ⊿FEV1%) (P > 0.05). Conclusions The severity of emphysema measured by HRCT is well correlated with the clinical symptoms , pulmonary function tests and exercise capacity in COPD patients. It can be used to diagnose emphysema early and to evaluate the severity of the disease com-prehensively. Thus, the risk factors of COPD can be controlled and the prognosis of the patients can be im-proved.