Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection.

Pathogen encounter results in long-lasting epigenetic imprinting that shapes diseases caused by heterologous pathogens. The breadth of this innate immune memory is of particular interest in the context of respiratory pathogens with increased pandemic potential and wide-ranging impact on global health. Here, we investigated epigenetic imprinting across cell lineages in a disease relevant murine model of SARS-CoV-2 recovery. Past SARS-CoV-2 infection resulted in increased chromatin accessibility of type I interferon (IFN-I) related transcription factors in airway-resident macrophages. Mechanistically, establishment of this innate immune memory required viral pattern recognition and canonical IFN-I signaling and augmented secondary antiviral responses. Past SARS-CoV-2 infection ameliorated disease caused by the heterologous respiratory pathogen influenza A virus. Insights into innate immune memory and how it affects subsequent infections with heterologous pathogens to influence disease pathology could facilitate the development of broadly effective therapeutic strategies.

[Analysis on the rationality of input and output of occupational health funds in an iron and steel enterprise].

Objective: To analyzes the various occupational health investment and occupational health output of a steel enterprise, and propose a reasonable occupational health investment plan for this enterprise. Methods: In march 2016, various occupational health input and output data of various branches of an iron and steel company in 2015 were collected, and the efficiency of occupational health inputs and outputs of each branch was evaluated using data envelopment analysis (DEA) , and the branches with non-optimal efficiency were adjusted to propose a reasonable occupational health investment plan. Results: Among the branch plants investigated by this steel company, the occupational health input-output efficiency values of ironmaking north plant, power plant, hot rolling plant and stainless steel plant were 1, while the occupational health input-output efficiency of gas making plant, cold rolling plant, metallurgical furnace charge plant, coking plant, ironmaking south plant and long product plant were not the best, and the cold rolling plant has the lowest efficiency value of 0.759. For the cold rolling plant, only the parameters of acid rolling plant satisfy α=1 and s(-)=0, s(+)=0, while the remaining four workshops do not meet. After adjusting the inputs of each part according to the parameters, the occupational health output of the remaining four workshops can reach 1.7044, 2.0238, 1.3152 and 1.2136 times of the current workshop, respectively. Adjustment plans for other branch factories with unreasonable investment structures are also presented in the corresponding tables. Conclusion: The occupational health investment structure of the ironmaking south plant and other branches in this steel enterprise is unreasonable, and the adjustment using data envelopment analysis can maximize the benefits of its occupational health output.

[Application of Raman-based technologies in the detection of urological tumors].

Urinary system tumors affect a huge number of individuals, and are frequently recurrent and progressing following surgery, necessitating lifelong surveillance. As a result, early and precise diagnosis of urinary system cancers is important for prevention and therapy. Histopathology is now the golden stan-dard for the diagnosis, but it is invasive, time-consuming, and inconvenient for initial diagnosis and re-gular follow-up assessment. Endoscopy can directly witness the tumor's structure, but intrusive detection is likely to cause harm to the patient's organs, and it is apt to create other hazards in frequently examined patients. Imaging is a valuable non-invasive and quick assessment tool; however, it can be difficult to define the type of lesions and has limited sensitivity for early tumor detection. The conventional approaches for detecting tumors have their own set of limitations. Thus, detection methods that combine non-invasive detection, label-free detection, high sensitivity and high specificity are urgently needed to aid clinical diagnosis. Optical diagnostics and imaging are increasingly being employed in healthcare settings in a variety of sectors. Raman scattering can assess changes in molecular signatures in cancer cells or tissues based on the interaction with vibrational modes of common molecular bonds. Due to the advantages of label-free, strong chemical selectivity, and high sensitivity, Raman scattering, especially coherent Raman scattering microscopy imaging with high spatial resolution, has been widely used in biomedical research. And quantity studies have shown that it has a good application in the detection and diagnosis of bladder can-cer, renal clear cell carcinoma, prostate cancer, and other cancers. In this paper, several nonlinear imaging techniques based on Raman scattering technology are briefly described, including Raman spectroscopy, coherent anti-Stokes Raman scattering, stimulated Raman scattering, and surface-enhanced Raman spectroscopy. And we will discuss the application of these techniques for detecting urologic malignancy. Future research directions are predicted using the advantages and limitations of the aforesaid methodologies in the research. For clinical practice, Raman scattering technology is intended to enable more accurate, rapid, and non-invasive in early diagnosis, intraoperative margins, and pathological grading basis for clinical practice.

[Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen].

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

Simulation-based design study for the passive shielding of the COSINUS dark matter experiment.

The COSINUS (Cryogenic Observatory for SIgnatures seen in Next-generation Underground Searches) experiment aims at the detection of dark matter-induced recoils in sodium iodide (NaI) crystals operated as scintillating cryogenic calorimeters. The detection of both scintillation light and phonons allows performing an event-by-event signal to background discrimination, thus enhancing the sensitivity of the experiment. The choice of using NaI crystals is motivated by the goal of probing the long-standing DAMA/LIBRA results using the same target material. The construction of the experimental facility is foreseen to start by 2021 at the INFN Gran Sasso National Laboratory (LNGS) in Italy. It consists of a cryostat housing the target crystals shielded from the external radioactivity by a water tank acting, at the same time, as an active veto against cosmic ray-induced events. Taking into account both environmental radioactivity and intrinsic contamination of materials used for cryostat, shielding and infrastructure, we performed a careful background budget estimation. The goal is to evaluate the number of events that could mimic or interfere with signal detection while optimising the geometry of the experimental setup. In this paper we present the results of the detailed Monte Carlo simulations we performed, together with the final design of the setup that minimises the residual amount of background particles reaching the detector volume.

Increased odds ratio for erectile dysfunction in COVID-19 patients.

PURPOSE: Erectile dysfunction and COVID-19 share similar risk factors, including vascular disruption of integrity, cytokine release, cardiovascular disease, diabetes and obesity. The aim of this study was to investigate the association between erectile dysfunction and COVID-19 patients. METHODS: Odds ratio for erectile dysfunction in patients with a history of COVID-19 with and without comorbidities were calculated using a patients' registry platform i2b2. ICD-10 diagnoses codes were accessed for queries and data were analyzed using logistic regression. RESULTS: Patients with COVID-19 were 3.3 times more likely to have erectile dysfunction with 95% CI (2.8, 3.8). The association became stronger with odds ratio 4.8 (95% CI (4.1, 5.7)) after adjusting for age groups. The odds ratio remained the same after adjusting for smoking status with 3.5 (95% CI (3.0, 4.1)). After adjusting for race, COVID-19 patients were 2.6 (95% CI (2.2, 3.1)) times more likely to have erectile dysfunction. The odds ratio were 1.6, 1.8, 1.9 and 2.3 after adjusting for respiratory disease, obesity, circulatory disease and diabetes, respectively. CONCLUSION: COVID-19 and erectile dysfunction are strongly associated even after adjustment for known risk factors and demographics.

[Analysis of occupational health input-output of a iron mine in Hebei province].

Objective: To explore the relationship between input and output of occupational health funds, and to provide basis for relevant departments to make decisions. Methods: In September 2018, a state-owned iron ore in Hebei Province (mining history of more than 10 years, which can represent the general type of iron ore) was selected as the research object. Through the investigation and collection of enterprise general situation, occupational health input, loss and output related indicators, the iron mine occupational health expenditure input-output table and model were established, and the digital relationship between the investment and output was solved by MATLAB software. Results: The labor consumption in the departments of underground mining, open pit mining, crushing and rock discharging, transportation, tailings and mineral processing (taking labor wages as reference) were 756.46, 1.281.78, 987.61, 1 570.71, 50.956 and 18.9116 million yuan/year respectively. The output value of each sector is 11 207.19, 18 989.95, 15 176.40, 25 294.00, 7.704.94 and 280.1797 million yuan/year respectively. The ratio of health input to total output was 0.004 5, and the ratio of occupational health input to output was 1/0.046. Conclusion: The input-output table model of occupational health in iron mine can reflect the relationship between input and output of occupational health funds. The input situation of the coal mine is poor, and the input does not bring obvious occupational health benefits.

[Clinical characteristics and prognosis of 49 newly diagnosed primary central nervous system diffuse large B-cell lymphoma].

Objective: The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively. Methods: A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis. Results: The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively (P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively (P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion: The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

MiR-125b Improves acute myocardial infarction in rats by regulating P38/Sirtl/P53 signaling pathway.

The aim of this study was to investigate the differential expression of micro ribonucleic acid (miR)- 125b in acute myocardial infarction (AMI) cases, and to explore the mechanism by which it affects cardiac function. Sprague-Dawley rats were used for AMI modeling, and the expression of miR-125b in the myocardial tissues of AMI rats was detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Thereafter, the target genes of miR-125b were collected and uploaded to WenGestalt for gene ontology (GO) and pathway enrichment analyses. In-vitro experiments were then applied to determine the p38-sirtuin 1 (Sirt1)-p53 expression change and cardiomyocyte apoptosis under down-regulation of miR-125b. Next, the interaction between miR-125b and its target genes was verified by luciferase reporter gene assay. The expression of miR-125b in the cardiac tissues was decreased in theAMI group compared with that in the Sham group (p<0.05). The luciferase reporter gene assay confirmed that p38 was the target gene of miR-125b. Furthermore, the down-regulated expression of miR-125b in H9C2 cells up-regulated the protein expressions of p38 and phosphorylated p38, thus activating the Sirt1-p53 signaling pathway. Moreover, the down-regulation of miR-125b expression in H9C2 cells gave rise to the elevated apoptosis rate, and the down-regulated expression of miR-125b induced cardiomyocyte apoptosis through activating the p38-Sirt1-p53 signaling pathway.

Gut microbiota and metabolites in the pathogenesis of endocrine disease.

Type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT) are the two most common autoimmune endocrine diseases that have rising global incidence. These diseases are caused by the immune-mediated destruction of hormone-producing endocrine cells, pancreatic beta cells and thyroid follicular cells, respectively. Both genetic predisposition and environmental factors govern the onset of T1D and HT. Recent evidence strongly suggests that the intestinal microbiota plays a role in accelerating or preventing disease progression depending on the compositional and functional profile of the gut bacterial communities. Accumulating evidence points towards the interplay between the disruption of gut microbial homeostasis (dysbiosis) and the breakdown of host immune tolerance at the onset of both diseases. In this review, we will summarize the major recent findings about the microbiome alterations associated with T1D and HT, and the connection of these changes to disease states. Furthermore, we will discuss the potential mechanisms by which gut microbial dysbiosis modulates the course of the disease, including disruption of intestinal barrier integrity and microbial production of immunomodulatory metabolites. The aim of this review is to provide broad insight into the role of gut microbiome in the pathophysiology of these diseases.

Effects of a nutrient-dense formula compared with a post-discharge formula on post-discharge growth of preterm very low birth weight infants with extrauterine growth retardation: a multicentre randomised study in China.

BACKGROUND: Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR. METHODS: Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected. RESULTS: Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry. CONCLUSIONS: After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up.

Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab.

Romosozumab is a therapy that stimulates bone formation and reduces bone resorption. In this study of postmenopausal women with low BMD, a second course of romosozumab following a period off treatment or on denosumab increased or maintained BMD, respectively, and was well tolerated, providing insight into treatment sequence options. INTRODUCTION: In patients with high fracture risk, therapies that stimulate bone formation provide rapid BMD gains; currently available agents, parathyroid hormone receptor agonists, are limited to a 2-year lifetime exposure and generally used for a single treatment course. However, for long-term osteoporosis management, a second treatment course may be appropriate. Romosozumab, a therapy with the dual effect of increasing bone formation and decreasing bone resorption, reduces fracture risk within 12 months. Here, we report efficacy and safety of a second romosozumab course. METHODS: In this phase 2, dose-finding study, postmenopausal women with low bone mass (T-score ≤ - 2.0 and ≥ - 3.5) received romosozumab or placebo (month 0-24) followed by placebo or denosumab (month 24-36); participants then received a year of romosozumab (month 36-48). RESULTS: Of 167 participants who entered the month 36-48 period, 35 had been initially randomized to romosozumab 210 mg monthly. In participants who received romosozumab 210 mg monthly followed by placebo, a second romosozumab course (n = 19) increased BMD by amounts similar to their initial treatment (month 0-12) at the lumbar spine (12.4%; 12.0%, respectively) and total hip (6.0%; 5.5%, respectively). Following denosumab, a second romosozumab course (n = 16) increased BMD at the lumbar spine (2.3%) and maintained BMD at the total hip. Safety profiles were similar between first and second romosozumab courses. CONCLUSIONS: After 12 months off-treatment, a second romosozumab course again led to rapid and large BMD gains. Following denosumab, BMD gains with romosozumab were smaller than with initial treatment. No new safety findings were observed during the second course.

An accurate and powerful method for copy number variation detection.

MOTIVATION: Integration of multiple genetic sources for copy number variation detection (CNV) is a powerful approach to improve the identification of variants associated with complex traits. Although it has been shown that the widely used change point based methods can increase statistical power to identify variants, it remains challenging to effectively detect CNVs with weak signals due to the noisy nature of genotyping intensity data. We previously developed modSaRa, a normal mean-based model on a screening and ranking algorithm for copy number variation identification which presented desirable sensitivity with high computational efficiency. To boost statistical power for the identification of variants, here we present a novel improvement that integrates the relative allelic intensity with external information from empirical statistics with modeling, which we called modSaRa2. RESULTS: Simulation studies illustrated that modSaRa2 markedly improved both sensitivity and specificity over existing methods for analyzing array-based data. The improvement in weak CNV signal detection is the most substantial, while it also simultaneously improves stability when CNV size varies. The application of the new method to a whole genome melanoma dataset identified novel candidate melanoma risk associated deletions on chromosome bands 1p22.2 and duplications on 6p22, 6q25 and 19p13 regions, which may facilitate the understanding of the possible roles of germline copy number variants in the etiology of melanoma. AVAILABILITY AND IMPLEMENTATION: http://c2s2.yale.edu/software/modSaRa2 or https://github.com/FeifeiXiaoUSC/modSaRa2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Taking Control of Your Surgery: Impact of a Prehabilitation Program on Major Abdominal Surgery.

BACKGROUND: Surgery is a major physiologic stress comparable to intense exercise. Diminished cardiopulmonary reserve is a major predictor of poor outcomes. Current preoperative workup focuses mainly on identifying risk factors; however, little attention is devoted to improving cardiopulmonary reserve beyond counseling. We propose that patients could be optimized for a "surgical marathon" similar to the preparation of an athlete. STUDY DESIGN: The Michigan Surgical and Health Optimization Program (MSHOP) is a formal prehabilitation program that engages patients in 4 activities before surgery: physical activity, pulmonary rehabilitation, nutritional optimization, and stress reduction. We prospectively collected demographic, intraoperative (first hour), and postoperative data for patients enrolled in MSHOP undergoing major abdominal surgery. Statistical analysis was performed using 2:1 propensity score matching to compare the MSHOP group (n = 40) to emergency (n = 40) and elective, non-MSHOP (n = 76) patients. RESULTS: Overall, 70% of MSHOP patients complied with the program. Age, sex, American Society of Anesthesiologists (ASA) classification, and BMI did not differ significantly between groups. One hour intraoperatively, MSHOP patients showed improved systolic and diastolic blood pressures and lower heart rate (Figure). There was a significant reduction in Clavien-Dindo class 3 to 4 complications in the MSHOP group (30%) compared with the nonprehabilitation (38%) and emergency (48%) groups (p = 0.05). This translated to total hospital charges averaging $75,494 for the MSHOP group, $97,440 for the nonprehabilitation group, and $166,085 for the emergency group (p < 0.001). CONCLUSIONS: Patients undergoing prehabilitation before colectomy showed positive physiologic effects and experienced fewer complications. The average savings of $21,946 per patient represents a significant cost offset for a prehabilitation program, and should be considered for all patients undergoing surgery.

[Effect of biofeedback therapy on metabolic syndrome under different levels of job stress].

Objective: To investigate the effect of biofeedback therapy on metabolic syndrome (MS) and the effect of different levels of job stress on the outcome. Methods: The physicians in tertiary hospitals who were diagnosed with MS from January to December, 2016 were divided into biofeedback group and health education group according to different intervention methods, and moderate group, medium group, and high group according to different levels of job stress. A 6-month intervention was implemented from May to October, 2017. A two-way factorial design was used to analyze the main effect of biofeedback on physical and biochemical parameters and the interaction of biofeedback and job stress. Results: After 6 months of intervention, the patients in both the biofeedback group and the moderate group had significantly decreased waist circumference, body mass index, systolic blood pressure (SBP) , diastolic blood pressure (DBP) , and levels of triglyceride (TG) , total cholesterol, low-density lipoprotein cholesterol (LDL-C) , and fasting plasma glucose (FPG) and a significantly increased level of high-density lipoprotein cholesterol (HDL-C) (all P<0.05) ; the patients in both the health education group and the moderate group had significantly decreased SBP, DBP, and levels of TG, LDL-C, and FPG (P<0.05) . The factorial analysis of variance showed that there was a synergistic interaction between the intervention method and job stress level in SBP, DBP, TG, HDL-C, LDL-C, and FPG among MS patients (P<0.05) . The high group had significantly more improvements in all indices compared with the medium group and the moderate group (P<0.05) . Conclusion: Biofeedback therapy can effectively improve blood pressure, blood lipids, and blood glucose in MS patients, and is more effective for patients with high job stress level.

[Clipping for large paraclinoid internal carotid artery aneurysms by non-fluoroscopic occlusion via a micro-bone window frontolateral approach].

Objective: To evaluate the clinical value and outcomes of technical improvement of hybrid operatical clipping for large paraclinoid internal carotid artery aneurysms. Methods: A review was conducted on 18 cases of large paraclinoid internal carotid artery aneurysm which were clipped by balloon non-fluoroscopic occlusion of the parent artery via a micro-bone window frontolateral approach in hybrid operating room at Neurosurgery Department of Tianjin Medical University General Hospital from June 2014 to December 2017. There were 8 males and 10 females with age of (63±4) years. There were 6 cases of unruptured aneurysm and 12 cases of ruptured aneurysm of subarachnoid hemorrhage (6 cases of grade Ⅱ, 4 cases of grade Ⅲ and 2 cases of grade Ⅳ in Hunt-Hess classification). Frontolateral approach incision (average length of about 5 cm) and bone window about 3 cm×3 cm were performed. No incision of the neck was needed to expose the internal carotid artery for temporary occlusion. In the operation, the balloon was slowly pushed to the preset position of the internal carotid artery under non-fluoroscopy. The balloon was expanded to block the blood flow of internal carotid artery. Then aneurysm was clipped. The balloon was loosened and retraced to the guiding catheter after clipping. The clipping condition was examined by cerebral angiography. If there was residual aneurysm neck or stenosis of the parent artery, the balloon was pushed under non-fluoroscopy again to temporary occlusion and the clip was adjusted until the aneurysm neck was clamped satisfactorily. Results: Eighteen aneurysms were successfully clipped in hybrid operating room. Fourteen aneurysms showed complete occlusion of the aneurysm neck and no stenosis of the parent artery. Four cases showed residual aneurysm neck after clipping by intraoperative angiography, then aneurysms were clipped satisfy by adjusting the aneurysm clip. The patients were followed up for 3 months to 1 year. Ten patients recovered well (modifed Rankin score (mRS): 0), and 3 patients had no obvious disability (mRS: 1). Two patients with Hunt-Hess grade Ⅲ were slightly disabled (mRS: 2). 1 patients with Hunt-Hess grade Ⅲ were moderately disabled (mRS: 3). 1 patients with Hunt-Hess grade Ⅳ were severely disabled (mRS: 4). One elderly patients with Hunt-Hess grade Ⅳ were seriously disabled (mRS: 5). Conclusions: Application of balloon non-fluoroscopic occlusion clipping for large paraclinoid internal carotid artery aneurysm via a micro-bone window frontolateral approach is safe, effective and minimally invasive.