Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Background and Purpose-Early hematoma growth is not uncommon in patients with intracerebral hemorrhage and is an independent predictor of poor functional outcome. The purpose of our study was to report and validate the use of our newly identified computed tomographic (CT) blend sign in predicting early hematoma growth. Methods-Patients with intracerebral hemorrhage who underwent baseline CT scan within 6 hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Significant hematoma growth was defined as an increase in hematoma volume of >33% or an absolute increase of hematoma volume of >12.5 mL. The blend sign on admission nonenhanced CT was defined as blending of hypoattenuating area and hyperattenuating region with a well-defined margin. Univariate and multivariable logistic regression analyses were performed to assess the relationship between the presence of the blend sign on nonenhanced admission CT and early hematoma growth. Results-A total of 172 patients were included in our study. Blend sign was observed in 29 of 172 (16.9%) patients with intracerebral hemorrhage on baseline nonenhanced CT scan. Of the 61 patients with hematoma growth, 24 (39.3%) had blend sign on admission CT scan. Interobserver agreement for identifying blend sign was excellent between the 2 readers (κ=0.957). The multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and presence of blend sign on baseline CT scan to be independent predictors of early hematoma growth. The sensitivity, specificity, positive and negative predictive values of blend sign for predicting hematoma growth were 39.3%, 95.5%, 82.7%, and 74.1%, respectively. Conclusions-The CT blend sign could be easily identified on regular nonenhanced CT and is highly specific for predicting hematoma growth.

BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is increasingly acknowledged as a separate syndrome with distinct clinical, physiological and radiological characteristics. We sought to identify physiologic and radiographic indices that predict mortality in CPFE.MethodsData on clinical characteristics, pulmonary function, high-resolution computed tomography (HRCT) and treatment were compared between patients with usual interstitial pneumonia (UIP) plus emphysema (CPFE group) and those with IPF alone (IPF group). Composite physiologic index (CPI) and HRCT scores at diagnosis and during follow-up were assessed.ResultsCPFE group (N = 87) was characterized by the predominance of males and smokers, who were less likely to have viral infection prior to the diagnosis, and display basal crackles, finger clubbing and wheeze, as compared to that in the IPF group (N = 105). HRCT and CPI scores increased over time in both groups. Moreover, CPFE group had a poorer prognosis, lower 5-year survival rate (43.42 % vs. 65.56 %; P < 0.05), and higher mortality (39.47 % vs. 23.33 %; P < 0.05) as compared to that in the IPF group. All CPFE patients received oxygen therapy, antibiotics and oral N-acetylcysteine; > 50 % received bronchodilators, 40 % received corticosteroids and 14 % needed noninvasive mechanical ventilation. On survival analyses, pulmonary arterial hypertension (PAH) and ≥ 5-point increase in CPI score per year were predictors of mortality in the CPFE group (hazard ratio [HR]: 10.29, 95 % Confidence Interval [CI]: 2.69–39.42 and HR: 21.60, 95 % CI: 7.28–64.16, respectively).ConclusionPatients with CPFE were predominantly male and smokers and exhibited distinct clinical, physiological and radiographic characteristics. They had a poorer prognosis than IPF. PAH and ≥ 5-point increase in CPI score per year were predictors of mortality in these patients. Future studies are needed to identify the optimal treatment approach to CPFE.

medRxiv preprint 17. WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf. 18. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39(5): 529-39. 19. Huang KJ, Su IJ, Theron M, et al. An interferon-gamma-related cytokine storm in SARS patients.J Med Virol 2005; 75(2): 185-94. 20. Jiang Y, Xu J, Zhou C, et al. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med 2005; 171(8): 850-7. 21. Ying T, Prabakaran P, Du L, et al. Junctional and allele-specific residues are critical for All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Background and Aim: Helicobacter pylori infection has been reported to promote the development of a variety of extra-digestive manifestations, including type 2 diabetes, cardiovascular and liver diseases. Recently, the association between H. pylori infection and non-alcoholic fatty liver disease (NAFLD) was also proposed. However, evidence from different studies was controversial. We therefore performed this study to investigate the relationship between them in a large population of apparently healthy subjects in China.Methods: A total of 21,456 subjects underwent a healthy checkup program were included. H. pylori infection was detected by 14C urea breath test (14C-UBT) and NAFLD was diagnosed by ultrasonography.Results: Subjects infected with H. pylori had a more unfavorable metabolic profile, including higher levels of body mass index (BMI), blood pressure, triglycerides (TG) and lower levels of high-density lipoprotein cholesterol (HDL-C), as compared with those without H. pylori infection (all P < 0.05). Moreover, the prevalence rate of NAFLD was significantly increased in subjects with H. pylori infection when compared with those without H. pylori in women (23.6% vs. 21.5%, P < 0.05), but not in men (46.5% vs. 45.5%, P > 0.05). After adjusting for confounding factors including age, sex, BMI, blood pressure and lipid profiles, multivariate logistic analysis revealed that H. pylori infection was not independently associated with the risk of NAFLD in the total population (OR = 0.9, 95% CI = 0.9–1.0, P = 0.097). Also, subgroup analysis (stratified by age, sex, BMI, and diabetes status) showed no independent association between H. pylori infection and NAFLD.Conclusion: Our data suggests that H. pylori infection is not independently associated with the risk of NAFLD in apparently healthy subjects.

IMPORTANCE A randomized clinical trial is needed to evaluate what is the best photodynamic therapy (PDT) protocol to use for acute central serous chorioretinopathy.OBJECTIVE To compare the efficacy and safety of a 50% dose of verteporfin (a method of PDT) with the efficacy and safety of a 30% dose for acute central serous chorioretinopathy. DESIGN, SETTING, AND PARTICIPANTSA multicenter, noninferiority, double-masked, randomized, controlled, clinical trial in which 131 patients (131 eyes) with acute central serous chorioretinopathy for less than 6 months were recruited with a follow-up of 12 months from university-based ophthalmology practices.INTERVENTIONS Patients were randomly assigned to either a 50% dose of verteporfin (the 50%-dose PDT group) or a 30% dose (the 30%-dose PDT group). MAIN OUTCOMES AND MEASURESThe 2 primary outcome measures were the proportion of eyes with complete absorption of subretinal fluid and the proportion of eyes with complete disappearance of fluorescein leakage at 6 and 12 months. The secondary outcome measures included the subretinal fluid recurrent rate, the fluorescein leakage recurrent rate at 12 months, the mean best-corrected visual acuity, the retinal thickness of the foveal center, and the maximum retinal thickness at each scheduled visit. RESULTSThe noninferiority of the 30%-dose PDT compared with the 50%-dose PDT for the primary outcomes was not demonstrated. The optical coherence tomography-based improvement rate in the 30%-dose PDT group was less than that in the 50%-dose PDT group both at 6 months (73.8% vs 92.9%; α = 0.0125, P = .006) and at 12 months (75.4% vs 94.6%; α = 0.0125, P = .004). The fluorescein angiography-based improvement rate in the 30%-dose PDT group was less than that in the 50%-dose PDT group both at 6 months (68.9% vs 91.1%; α = 0.0125, P = .003) and at 12 months (68.9% vs 92.9%; α = 0.0125, P = .001). The subretinal fluid recurrence rate in the 30%-dose PDT group was greater than that in the 50%-dose PDT group (24.0% vs 5.7% at 12 months; P = .010, determined by use of the log-rank test). The fluorescein leakage recurrent rate in the 30%-dose PDT group was significantly higher than that in the 50%-dose PDT group (16.7% vs 3.8% at 12 months; P = .03, determined by use of the log-rank test). No ocular adverse event was encountered in the study. CONCLUSIONS AND RELEVANCEA 50% dose of verteporfin may be more effective at resolving subretinal fluid and fluorescein leakage, and with better visual outcomes, than a 30% dose for acute central serous chorioretinopathy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01574430

Despite two centuries of reports linking alcohol consumption with enhanced susceptibility to bacterial infections and in particular gut-derived bacteria, there have been no studies or model systems to assess the impact of long-term alcohol exposure on the ability of the epithelial barrier to withstand bacterial infection. It is well established that acute alcohol exposure leads to reduction in tight and adherens junctions, which in turn leads to increases in epithelial cellular permeability to bacterial products, leading to endotoxemia and a variety of deleterious effects in both rodents and human. We hypothesized that reduced fortification at junctional structures should also reduce the epithelial barrier’s capacity to maintain its integrity in the face of bacterial challenge thus rendering epithelial cells more vulnerable to infection. In this study, we established a cell-culture based model system for long-term alcohol exposure to assess the impact of chronic alcohol exposure on the ability of Caco-2 intestinal epithelial cells to withstand infection when facing pathogenic bacteria under the intact or wounded conditions. We report that daily treatment with 0.2% ethanol for two months rendered Caco-2 cells far more susceptible to wound damage and cytotoxicity caused by most but not all bacterial pathogens tested in our studies. Consistent with acute alcohol exposure, long-term ethanol exposure also adversely impacted tight junction structures, but in contrast, it did not affect the adherens junction. Finally, alcohol-treated cells partially regained their ability to withstand infection when ethanol treatment was ceased for two weeks, indicating that alcohol’s deleterious effects on cells may be reversible.

Objectives We herein aimed to explore whether growth arrest‐specific 5 (GAS5) promotes M1 macrophage polarization in childhood pneumonia and to investigate the underlying mechanism. Methods Relative GAS5 and miR‐455‐5p expression and suppressor of cytokine signaling 3 (SOCS3) messenger RNA level were examined using quantitative reverse transcription polymerase chain reaction. Protein expression of SOCS3 and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway‐related proteins was detected using western blot analysis. Luciferase activity assay was performed to test whether miR‐455‐5p could bind to GAS5 or SOCS3. The macrophage phenotype was determined using flow cytometry analysis and enzyme‐linked immunosorbent assay. Results The macrophage polarization toward the M2 phenotype was observed in peripheral blood from pneumonia children. Furthermore, GAS5 and SOCS3 expression were upregulated but miR‐455‐5p downregulated in human monocyte‐derived macrophages from pneumonia children compared with the control group. Furthermore, GAS5 acted as a sponge for miR‐455‐5p to facilitate SOCS3 expression. Moreover, miR‐455‐5p mimic and SOCS3 knockdown significantly reversed the GAS5 overexpression‐mediated suppression of the JAK2/STAT3 signaling and promotion of M1 polarization. Conclusion GAS5 promotes M1 macrophage polarization by acting as a competing endogenous RNA of miR‐455‐5p to facilitate SOCS3 expression in childhood pneumonia.