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Endotoxins carried within LDL are cleared from the circulation via hepatic LDL receptor (LDLR)-mediated endocytosis. Proprotein convertase subtilisin-kexin type 9 (PCSK9) reduces this clearance by down-regulating LDLR density on hepatocytes. In addition to hepatocytes, vascular endothelial cells also express receptor targets of PCSK9, including LDLR. Therefore, we hypothesized that PCSK9 may regulate vascular endothelial cell uptake of lipopolysaccharide (LPS) and alter the vascular endothelial cell inflammatory response.We found that LPS is internalized by human umbilical vein vascular endothelial cells (HUVECs) and LPS uptake dose-dependently increased with increasing LDL concentration. Intracellular LPS co-localized with LDL. PCSK9 and, separately, blocking antibodies against LDLR, dose-dependently decreased the vascular endothelial cell uptake of LPS and, furthermore, inhibition of endocytosis using Dynasore blocked LPS uptake. In contrast, blocking antibodies against TLR4 did not alter LPS uptake. PCSK9 decreased the LPS-induced proinflammatory response (IL-6 and IL-8 gene expression and protein secretion, and VCAM-1/ICAM-1 expression) in vascular endothelial cells. In addition, a decrease in PCSK9 and increase in LDLR, mediated by triciribine or siPCSK9, increased LPS uptake and the LPS-induced proinflammatory response. Similar results were also found in aortic vascular tissue from Pcsk9Our data suggest that, similar to PCSK9 treatment in hepatocytes, PCSK9 reduces vascular endothelial cell uptake of LPS via LDLR-mediated endocytosis. Consequently, PCSK9 decreases the LPS-induced proinflammatory response in vascular endothelial cells. These results raise the possibility that PCSK9 inhibition may have additional effects on vascular endothelial inflammation via this alternative pathway, beyond the known effects of PCSK9 inhibition on LDL lowering and hepatic endotoxin clearance.

The aim of the study described here was to assess the evaluation of tissue stiffness around lesions by sound touch shear wave elastography (STE) in breast malignancy diagnosis. This was an institutional ethics committee-approved, single-center study. A total of 90 women with breast masses examined with conventional ultrasound and STE were eligible for enrollment from December 2020 to July 2021. The maximum and mean elastic values of masses, E

Neocentromeres develop when kinetochores assemble de novo at DNA loci that are not previously associated with CenH3 nucleosomes, and can rescue rearranged chromosomes that have lost a functional centromere. The molecular mechanisms associated with neocentromere formation in plants have been elusive. Here, we developed a Xian (indica) rice line with poor growth performance in the field due to approximately 272 kb deletion that spans centromeric DNA sequences, including the centromeric satellite repeat CentO, in the centromere of chromosome 8 (Cen8). The CENH3-binding domains were expanded downstream of the original CentO position in Cen8, which revealed a de novo centromere formation in rice. The neocentromere formation avoids chromosomal regions containing functional genes. Meanwhile, canonical histone H3 was replaced by CENH3 in the regions with low CENH3 levels, and the CenH3 nucleosomes in these regions became more periodic. In addition, we identified active genes in the deleted centromeric region, which are essential for chloroplast growth and development. In summary, our results provide valuable insights into neocentromere formation and show that functional genes exist in the centromeric regions of plant chromosomes.

Objective. We investigated the relationships between interleukin- (IL-) 1β and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN). Methods. The genotype and allele frequency distribution of IL-1β and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1β and IL-1Ra in DN patients and HCs were measured by enzyme-linked immunosorbent assays (ELISA). Results. Significant differences were detected in the distribution of IL-1β (−511C/T) genotype and allele frequencies between the DN and HC groups ( P < 0.05 ), with the T genotype being more frequent in DN patients than HCs ( OR = 2.84 , 95% CI: 1.489–5.416). The IL-1β (+3953C/T) and IL-1Ra (+8006C/T) genotypes and allele frequencies were not significantly different between the two groups ( P > 0.05 ). The plasma IL-1β level was significantly higher ( P < 0.01 ), while the plasma IL-1Ra concentration was significantly lower in the DN group than the HC group ( P < 0.05 ). Furthermore, the plasma IL-1β level was significantly different between IL-1β (−511C/T) locus variants ( P < 0.05 ). Conclusion. The IL-1β (−511C/T) gene polymorphism was significantly associated with DN risk in the population of northern Guangxi, China, and the T allele maybe responsible for genetic susceptibility to DN.

Isolating the causal genes from numerous genetic association signals in genome-wide association studies (GWASs) of complex phenotypes remains an open and challenging question. In the present study, we proposed a statistical approach, the effective-median-based Mendelian randomization (MR) framework, for inferring the causal genes of complex phenotypes with the GWAS summary statistics (named EMIC). The effective-median method solved the high false-positive issue in the existing MR methods due to either correlation among instrumental variables or noises in approximated linkage disequilibrium (LD). EMIC can further perform a pleiotropy fine-mapping analysis to remove possible false-positive estimates. With the usage of multiple cis-expression quantitative trait loci (eQTLs), EMIC was also more powerful than the alternative methods for the causal gene inference in the simulated datasets. Furthermore, EMIC rediscovered many known causal genes of complex phenotypes (schizophrenia, bipolar disorder, and total cholesterol) and reported many new and promising candidate causal genes. In sum, this study provided an efficient solution to discriminate the candidate causal genes from vast amounts of GWAS signals with eQTLs. EMIC has been implemented in our integrative software platform KGGSEE.

Anterior glottoplasty is a commonly used treatment for voice feminization. But it remains in dispute over whether to suture of the ligament as part of the procedure.This study aimed to explore the effect of inclusion of the vocal lamina propia.Anterior webs were created in 8 excised canine larynges by sutures placed at 10%, 20%, and 30% of the vocal fold length, respectively. The suture depth was divided into two groups: epithelium layer (Shallow Suture, SS group) and deep layers of vocal fold lamina propia (Deep Suture, DS group).For anterior webs between 0% and 30%, the frequency elevation ranged from 3% to 151% of the pre-web fundamental frequency (fo) in SS group and from 13% to 222% in DS group. No significance was found between two groups at three different sutures (The frequency in excised canine larynx increased continuously as the anterior glottic webs ranged from 0% to 30%. The inclusion of the vocal fold lamina propia does not affect the frequency elevation.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry metaanalysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) R01HL127564 R01HL142711, Wellcome Trust 201543/B/16/Z 202802/Z/16/Z, European Commission HEALTH-F2-2013-601456 608765 786833, TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation NNF15CC0018486, American Diabetes Association 1-19-ICTS-068, Academy of Finland 312062 Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation, Finnish innovation fund Sitra (EW) Finska Lakaresallskapet, American Heart Association 15POST24470131 17POST33650016, University of Bristol NIHR Biomedical Research Centre BRC-1215-2001, MRC & WT 217065/Z/19/Z, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) MC_UU_00011, CRUK Integrative Cancer Epidemiology Programme C18281/A19169, Medical Research Council UK (MRC) MC_UU_00011/1, UK National Institute for Health Research Academic Clinical Fellowship, American Heart Association 18CDA34110116, Miguel Servet contract from the ISCIII Spanish Health Institute CP17/00142, European Social Fund (ESF), Westlake Education Foundation, British Heart Foundation FS/14/66/3129 Z01HG200362 R01HL142302 R01HL105756

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM. Improving the Ability of Diagnosis and Treatment of Difficult Diseases

ObjectiveOpen microsurgery, often with bypass techniques, is indispensable for complex aneurysms. To date, it remains unknown whether arterial anatomy or quantitative blood flow measurements can predict insufficient flow-related stroke (IRS). The present study aimed to evaluate the risk factors for IRS in patients treated with open microsurgery with bypass procedures for complex internal carotid artery aneurysms.MethodsPatients with complex aneurysms undergoing bypass surgery were retrospectively reviewed. The recipient/donor flow index (RDFI) was preoperatively evaluated using colour-coding angiography. RDFI was defined as the ratio of the cerebral blood volume of the recipient and donor arteries. The sizes of the recipient and donor arteries were measured. The recipient/donor diameter index (RDDI) was then calculated. IRS was defined as the presence of new postoperative neurological deficits and infarction on postoperative CT scans. We assessed the association between RDFI and other variables and the IRS.ResultsTwenty patients (38±12 years) were analysed. IRS was observed in 12 patients (60%). Patients with postoperative IRS had a higher RDFI than those without postoperative IRS (p2.3 were more likely to develop IRS (pConclusionQuantitative digital subtraction angiography enables preoperative evaluation of cerebral blood volume. RDFI >2.3, rather than RDDI, was significantly associated with postoperative IRS. This preoperative evaluation allows appropriate decisions regarding the treatment strategy for preventing postoperative IRS.

ObjectiveRecent evidence has revealed that the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) may be closely associated with metabolic syndrome and insulin resistance. However, it is unclear whether the AST/ALT ratio correlates with prediabetes risk. The aim of our study was to examine the association between AST/ALT ratios and the risk of prediabetes among a large cohort of Chinese subjects.MethodsThis retrospective cohort study recruited 75204 Chinese adults with normoglycemia at baseline who underwent physical examinations at the Rich Healthcare Group from 2010 to 2016. The AST/ALT ratio at baseline was the target independent variable, and the risk of developing prediabetes during follow-up was the dependent variable. Cox proportional-hazards regression was used to evaluate the independent association between the AST/ALT ratio and prediabetes. This study identified nonlinear relationships by applying a generalized additive model (GAM) and smooth curve fitting. In order to assess the robustness of this study, we performed a series of sensitivity analyses. Moreover, we performed a subgroup analysis to evaluate the consistency of the association in different subgroups. Data from this study have been updated on the DATADRYAD website.ResultsThe AST/ALT ratio was negatively and independently related to the prediabetes risk among Chinese adults (HR: 0.76, 95% CI: 0.75-0.84, PConclusionThis study revealed that AST/ALT ratio was negatively and independently associated with prediabetes risk among Chinese participants. The relationship between the AST/ALT ratio and prediabetes risk was nonlinear, and AST/ALT ratio ≤ 1.50 was strongly inversely correlated with prediabetes risk.

Objectives Exposure to light at night (LAN) can disturb circadian endocrine and metabolic rhythms. Hyperuricemia (HUA) is an early-onset metabolic disorder. However, it is still not clear whether LAN exposure increases the prevalence of HUA. Material and Methods The authors used crosssectional data on the Beijing-Tianjin-Hebei occupational populations cohort from March–July 2017. A total of 7664 steel workers were finally selected to investigate the relationship between LAN exposure and the prevalence of HUA among steel workers. The authors collected demographic and socio-economic data, as well as information on lifestyle factors, anthropometric measures, and laboratory tests. The restricted cubic spline method was used to analyze the dose-response relationship between cumulative LAN exposure and the prevalence of HUA. Logistic regression analyses were used to fit the relationship between them. Results The average age of the participants was 43.5±8.6 years; 7051 (91.7%) of them were males, 2749 (35.9%) reported to suffer from HUA, and 1241 (16.2%) were not exposed to LAN. There was a significant non-linear dose-response relationship between them. After adjustment for the confounding factors, including demographic data, lifestyle factors, etc., the lower LAN exposure was significantly associated with HUA (0–1931.7 days, OR = 1.180, and the 95% CI: 1.000–1.394; 1931.7–4343 days, OR = 1.215, 95% CI: 1.035–1.426). Conclusions This study revealed that a certain amount of exposure to LAN is independently related to the prevalence of HUA in steel workers in China. Int J Occup Med Environ Health. 2021;34(3):385–401

AIMS The therapeutic effect of plasma exchange (PLEX) combined with conventional treatment in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. MATERIALS AND METHODS We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure for randomized controlled trials (RCTs) and cohort studies that compared PLEX added to conventional therapy with conventional therapy only in active AAV. RESULTS 19 studies were included for the meta-analysis. Compared with the conventional therapy group, the PLEX group had a significantly reduced risk of end-stage renal disease (ESRD) at 3 months (odds ratio (OR) = 0.32, 95% confidence interval (CI) = 0.16 - 0.66, p = 0.002, I2 = 0%), and the ANCA titerwas also decreased (OR = 40.99, 95% Cl = 23.56 - 58.43, p

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy-related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population.One hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case-control study. Multiplex polymerase chain reaction combined with high-throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis.rs4663402 and rs4663396 were in Hardy-Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D' = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03).Our results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.

To explore whether the post-left atrium space (PLAS) ratio would be useful for prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) using echocardiography and artificial intelligence.We retrospectively included 642 frames of four-chamber views from 319 fetuses (32 with TAPVC and 287 without TAPVC) in end-systolic and end-diastolic periods with multiple apex directions. The average gestational age was 25.6 ± 2.7 weeks. No other cardiac or extracardiac malformations were observed. The dataset was divided into a training set (n = 540; 48 with TAPVC and 492 without TAPVC) and test set (n = 102; 20 with TAPVC and 82 without TAPVC). The PLAS ratio was defined as the ratio of the epicardium-descending aortic distance to the center of the heart-descending aortic distance. Supervised learning was used in DeepLabv3+, FastFCN, PSPNet, and DenseASPP segmentation models. The area under the curve (AUC) was used on the test set.Expert annotations showed that this ratio was not related to the period or apex direction. It was higher in the TAPVC group than in the control group detected by the expert and the four models. The AUC of expert annotations, DeepLabv3+, FastFCN, PSPNet, and DenseASPP were 0.977, 0.941, 0.925, 0.856, and 0.887, respectively.Segmentation models achieve good diagnostic accuracy for TAPVC based on the PLAS ratio.

Background Approximately 80% of patients with blunt thoracic aortic injury (BTAI) die before reaching the hospital. Most people who survive the initial injury eventually die without appropriate treatment. This study analyzed and reported the treatment strategy of a single center for BTAI in the last 10 years and the early and middle clinical results. Methods This retrospective study included patients diagnosed with BTAI at Xijing Hospital from 2013 to 2022. All inpatients with BTAI aged ≥ 18 years were included in this study. The clinical data, imaging findings, and follow-up results were retrospectively collected and analyzed. The Kaplan–Meier curve and multivariate logistic regression were used to compare survivors and nonsurvivors. Results A total of 72 patients (57% men) were diagnosed with BTAI, with a mean age of 54.2 ± 9.1 years. The injury severity score was 24.3 ± 18, with Grade I BTAI1 (1.4%), Grade II 17 (23.6%), Grade III 52 (72.2%), and Grade IV 2 (2.8%) aortic injuries. Traffic accidents were the main cause of BTAI in 32 patients (44.4%). Most patients had trauma, 37 had rib fractures (51.4%), Sixty patients (83.3%) underwent thoracic endovascular aortic repair (TEVAR) surgery, eight (11.1%) underwent conservative treatment, and only four (5.6%) underwent open surgery. The overall hospitalization mortality was 12.5%. In multivariate logistic regression, elevated creatinine levels (P = 0.041) and high Glasgow coma scale (GCS) score (P = 0.004) were the predictors of hospital mortality. The median follow-up period was 57 (28–87) months. During the follow-up period, all-cause mortality was 5.6% and no aortic-related deaths were reported. Three patients (4.2%) needed secondary surgery and two of them underwent endovascular repair. Conclusion Although TEVAR surgery may be associated with intra- or postoperative dissection rupture or serious complications in the treatment of Grade III BTAI, the incidence rate was only 8.9%. Nevertheless, TEVAR surgery remains a safe and feasible approach for the treatment of Grade II or III BTAI, and surgical treatment should be considered first,. A high GCS score and elevated creatinine levels in the emergency department were closely associated with hospital mortality. Younger patients need long-term follow-up after TEVAR.

Background:. Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. Methods:. All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients’ selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. Results:. A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P

A study was conducted to determine whether iron-based phosphate binders (IBPBs) need to be preferred for hyperphosphatemia and anemia management in patients on dialysis. For this meta-analysis, we searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials that evaluated the efficacy and safety of IBPBs in decreasing phosphate and correcting anemia in dialysis patients. Nineteen trials comprising 4719 participants were included. Compared with placebo, serum phosphate decreased significantly after treatment with ferric citrate (FC), fermagate (one study), and SBR759 (one study). Hemoglobin increased significantly after treatment with FC and sucroferric oxyhydroxide (PA21). In addition, FC and PA21 reduced serum intact parathyroid hormone (iPTH) and increased ferritin and transferrin saturation, but SBR759 did not. Compared with active treatment, the non-inferiority of IBPBs in reducing serum phosphate and iPTH was demonstrated. FC significantly improved serum hemoglobin and iron-related parameters and decreased the use of intravenous iron and erythropoiesis-stimulating agent, whereas PA21 did not increase serum hemoglobin level. The incidences of infection and hospitalization were similar between the two groups, with FC having a higher risk of diarrhea than the placebo and active treatments. FC was associated with the control of hyperphosphatemia and the improvement of anemia. However, PA21 did not show superiority for alleviating anemia compared with the active treatment. Other IBPBs, such as fermagate and SBR759, remained poorly understood due to the limited number of studies. Further trials are required to assess the effect of IBPBs on the risk of cardiovascular events and all-cause mortality.

College and university students are a group known for excessive sun exposure and indoor tanning. Health education campaigns for avoidance of ultraviolet (UV) radiation have been relatively unsuccessful in this population. This systematic review examines interventions aimed at post-secondary school young adults on college and university campuses for skin cancer awareness, photoprotection, and change in UV-exposure-related behavior. Fifty-nine studies were identified for inclusion according to predetermined criteria. Study heterogeneity was high; methods of intervention were individual or group-based, and were mostly visually delivered and/or passive learning. Most interventions occurred at a single time point. Intervention success was assessed by evaluating subject behavior, intention, attitudes, knowledge, and emotion. Multicomponent interventions, generally consisting of UV photography and a passively delivered educational component, may be more effective than a single component alone. Overall, study quality was poor. Sample size of the majority of studies was

Schistosoma japonicum infections, which lead to local inflammatory responses to schistosome eggs trapped in host tissues, can result in long-term, severe complications. The development of schistosomiasis may result from a complex interaction between the pathogenic, environmental, and host genetic components. Notably, the genetic factors that influence the development of schistosomiasis complications are poorly understood. Here we performed a genome-wide association study on multiple schistosomiasis-related phenotypes of 637 unrelated schistosomiasis patients in the Chinese population. Among three indicators of liver damage, we identified two novel, genome-wide significant single-nucleotide polymorphisms (SNPs) rs34486793 (P = 1.415 × 10-8) and rs2008259 (P = 6.78 × 10-8) at locus 14q32.2 as well as a gene, PMEPA1, at 20q13.31 (index rs62205791, P = 6.52 × 10-7). These were significantly associated with serum levels of hyaluronic acid (HA). In addition, RASIP1 and MAMSTR at 19q13.33 (index rs62132778, P = 1.72 × 10-7) were significantly associated with serum levels of aspartate aminotransferase (AST), and TPM1 at 15q22.2 (index rs12442303, P = 4.39 × 10-7) was significantly associated with serum levels of albumin. In schistosomiasis clinical signs, ITIH4 at 3p21.1 (index rs2239548) was associated with portal vein diameter (PVD) class, an indicator of portal hypertension, and OGDHL at 10q11.23 (index rs1258172) was related to ascites grade. We also detected an increased expression of these six genes in livers of mice with severe schistosomiasis. Summary data-based Mendelian randomization analyses indicated that ITIH4, PMEPA1 and MAMSTR were pleiotropically associated with PVD class, HA and AST, respectively.

Oxidative stress and inflammation play key roles in development of pulmonary arterial hypertension (PAH). We previously reported that an endothelial cell (EC)-specific cyclophilin A overexpression mouse developed many characteristics of PAH. In other models of cardiovascular disease, cyclophilin A stimulates smooth muscle proliferation and vascular inflammation, but mechanisms responsible for PAH have not been defined. In particular, the contribution of endothelial-to-mesenchymal transition in cyclophilin A-mediated PAH has not been studied. We identified increased levels of cyclophilin A in endothelial and neointimal cells of pulmonary arteries in patients with PAH and animal pulmonary hypertension models. In the EC-specific cyclophilin A overexpression mouse that exhibited features characteristic of PAH, lineage tracing showed high level expression of mesenchymal markers in pulmonary ECs. A significant number of mesenchymal cells in media and perivascular regions of pulmonary arterioles and alveoli were derived from ECs. Pulmonary ECs isolated from these mice showed phenotypic changes characteristic of endothelial-to-mesenchymal transition in culture. Cultured pulmonary ECs stimulated with extracellular cyclophilin A and acetylated cyclophilin A demonstrated functional changes associated with endothelial-to-mesenchymal transition such as increased cytokine release, migration, proliferation, and mitochondrial dysfunction. Acetylated cyclophilin A stimulated greater increases for most features of endothelial-to-mesenchymal transition. In conclusion, extracellular cyclophilin A (especially acetylated form) contributes to PAH by mechanisms involving increased endothelial-to-mesenchymal transition, cytokine release, EC migration, proliferation, and mitochondrial dysfunction; strengthening the basis for studying cyclophilin A inhibition as a therapy for PAH.

Background: Osteosarcoma (OS) is a malignant tumor disease with high morbidity and mortality in children and adolescents. Recently, attention has been focused on the effects of long noncoding RNAs (lncRNAs) on tumor biology. In this study, we identified the role of lnc-SERTAD2-3 in the development of OS. Materials and Methods: Sixty OS samples and adjacent tissues were collected to determine the relationship between lnc-SERTAD2-3 levels and clinicopathological characteristics. Quantitative real-time PCR (qPCR) was used to measure gene expression levels. A transwell invasion assay, a Cell Counting Kit-8 assay, and flow cytometry were used to measure cell migration, growth, and apoptosis, respectively. The binding site between the lnc-SERTAD2-3 and miR-29c RNAs was evaluated using a luciferase reporter assay. Results: The expression of the lnc-SERTAD2-3 was significantly downregulated in OS samples and three OS cell lines (MG-63, U2OS, and Saos-2) compared to normal tissue. Patients with lower levels of lnc-SERTAD2-3 expression had a more unfavorable prognosis (larger OS size, distant metastasis, and recurrence). Overexpression of lnc-SERTAD2-3 inhibited proliferation and migration, and promoted apoptosis in OS cells. Moreover, we found that lnc-SERTAD2-3 could suppress miR-29c by direct binding. Moreover, reexpression of miR-29c reversed the effect of lnc-SERTAD2-3 on OS cells. Conclusion: Overall, lnc-SERTAD2-3, an OS suppressor, is involved in the inhibition of OS proliferation and migration by targeting miR-29c.

Whether autism spectrum disorder (ASD) is associated with a global processing deficit remains controversial. Global integration requires extraction of regularity across various timescales, yet little is known about how individuals with ASD process regularity at local (short timescale) versus global (long timescale) levels. To this end, we used event-related potentials to investigate whether individuals with ASD would show different neural responses to local (within trial) versus global (across trials) emotion regularities extracted from sequential facial expressions; and if so, whether this visual abnormality would generalize to the music (auditory) domain. Twenty individuals with ASD and 21 age- and IQ-matched individuals with typical development participated in this study. At an early processing stage, ASD participants exhibited preserved neural responses to violations of local emotion regularity for both faces and music. At a later stage, however, there was an absence of neural responses in ASD to violations of global emotion regularity for both faces and music. These findings suggest that the autistic brain responses to emotion regularity are modulated by the timescale of sequential stimuli, and provide insight into the neural mechanisms underlying emotional processing in ASD.

Innocent subjects who are knowledgeable of crime-related information will often be misclassified as "guilty" in P300-based complex trial protocol (CTP). Therefore, it is necessary to develop a more rigorous CTP that can effectively discriminate the guilty from both the knowledgeable and the unknowledgeable innocents. Sometimes the guilty and the knowledgeable innocents possess the same item memories but different source memories. The present study designed a novel item-source complex trial protocol based on the differences of source memory among the three kinds of individuals. Either the crime-related probe (e.g., the stolen ring) or one of the crime-unrelated stimuli (e.g., watch, earring, bracelet, or bangle) (item memory) was presented in the first part of each trail, and either a stealing-source word (e.g., stole) or other-source word (e.g., fetched) (source memory) was presented in the second part of each trail. The results showed that: (1) the P300 evoked by item memory could effectively discriminated the guilty from the unknowledgeable innocent (AUC = 0.76) but failed to effectively discriminate the guilty from the knowledgeable innocent (AUC = 0.60); (2) the late positive component evoked by source memory could effectively discriminated the guilty from both the knowledgeable innocent (AUC = 0.94) and the unknowledgeable innocent (AUC = 0.84) in one test.

Osteosarcoma, occurring most frequently in children, teens, and young adults, is a lethal bone cancer with a high incidence of distant metastases and drug resistance. Developing a therapeutic platform that integrates targeting, curing and imaging is highly desirable for enhanced osteosarcoma therapy, yet quite challenging. In this work, we demonstrate a novel biomineralization-inspired strategy for the synthesis of a fructose incorporated manganese phosphate (Fru-MnP) nanoplatform for tumour targeting, drug-free therapy, and MRI imaging. Benefitting from the glucose transporter 5 (GLUT5)-mediated endocytosis, our Fru-MnP nanoplatform produces a high level of reactive oxygen species (ROS)

To investigate the association of autophagy-associated gene 10 (ATG10) gene polymorphisms (rs1864182 and rs1864183) with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) in Chinese Guangxi population.The single nucleotide polymorphisms (SNPs) of ATG10 rs1864182 and rs1864183 in 395 participants (195 AAVs and 200 healthy controls) were genotyped. Generalized multiple dimensionality reduction (GMDR) was used to analyze the SNP-SNP interactions among two SNPs of ATG10 gene and other SNPs of autophagy gene previously studied by our research team.In this study, we found that the two ATG10 SNPs were not associated with AAV risk in Chinese Guangxi population. However, there were statistically significant differences in the incidence of hemoptysis, hematuria, and proteinuria among the three genotypes of ATG10 rs1864182 and rs1864183 (p 0.05). Moreover, permutation test of GMDR suggested that immunity-related GTPase M(IRGM) rs4958847, autophagy-associated gene 7 (ATG7) rs6442260, ATG7 rs2594966, ATG10 rs1864183, protein kinase B(AKT2) rs3730051, and AKT2 rs11552192 might interact with each other in the process of developing AAV (p 0.05).Our results indicated that there existed no association between ATG10 SNPs and AAV, and SNP-SNP interactions among IRGM rs4958847, ATG7 rs6442260, ATG7 rs2594966, ATG10 rs1864183, AKT2 rs3730051, and AKT2 rs11552192 may confer AAV risk in the Chinese Guangxi population.

BACKGROUND Congenital atrial appendage aneurysm (AAA) is a rare malformation which can coexist with potentially lethal complications. We aimed to summary echocardiographic characteristics and prognosis of fetal AAA. METHODS We retrospectively analyzed the echocardiographic data of 17 fetuses with AAA，and their outcomes or pathological reports were also collected. RESULTS Eight fetuses with left AAA (LAAA) and 9 fetuses with right AAA (RAAA) were identified. Five fetuses were diagnosed with other cardiac defects. Two fetuses with RAAA presented with arrhythmias, including atrial premature beats (n = 1) and bradyarrhythmia (n = 1). LAAA could be detected by four-chamber view (50.0%) and short-axis view (100.0%). RAAA could be detected by four-chamber view (100.0%), and view of right ventricular inflow tract (33.3%). There were three cases with mild pericardial effusion. Three cases with complex cardiac defects were selectively terminated, with confirmation of LAAA by autopsy in one case. Fourteen fetuses were born. After following 2 (range, 1-5) years, the AAA disappeared in one case with LAAA and two cases with RAAA. While, 11 cases were still diagnosed with AAA. Atrial premature beats with RAAA, which appeared in prenatal period, still persisted after birth. CONCLUSION Congenital AAA is a rare abnormality in utero. The short-axis view and the four-chamber view were the most useful views to detect fetal AAA. Fetal AAA may disappear in childhood. Atrial tachyarrhythmias in utero may exist persistently after birth. Patients with AAA should be followed up closely and appropriate intervention should be taken when complications appeared.

BACKGROUND Tranexamic acid (TXA) is safe and effective in total knee arthroplasty (TKA) for the prevention of bleeding. However, the role of TXA during unicompartmental knee arthroplasty (UKA) remains unclear. This study aimed to compare operative blood loss in patients undergoing UKA treated with an intra-articular injection of TXA with controls undergoing UKA without TXA. MATERIAL AND METHODS The prospective study included 101 patients who underwent UKA between January 2014 to March 2018. All patients completed a preoperative routine examination and were randomized to the study group (n=54) and the control group (n-47). The study group was given an articular injection of TXA (1.5 g in 50 ml normal saline) after the fascia was closed; the control group was injected with the same volume of normal saline. Blood volumes were measured from the drainage tube of the two groups during 48 hours. Total blood loss, postoperative drainage, hidden blood loss, blood transfusion rates, postoperative hemoglobin values, indicators of coagulation function, and the rates of wound complications were recorded. RESULTS Total blood loss in the study group was 745.6±105.1 ml, total drainage volume was 353.9±79.5 ml, and the hidden blood loss was 391.7±80.5 ml, which were all significantly lower when compared with the control group (P

The aim of this study was to quantify the effects of traditional and physiological warm-up exercises and to determine the optimal duration of these methods using acoustic and aerodynamic metrics.Twenty-six subjects were recruited to participate in both straw phonation exercises (physiological vocal warm-up) and traditional singing exercises (traditional vocal warm-up) for 20 minutes each, 24 hours apart. Phonation threshold pressure (PTP), fundamental frequency, jitter, shimmer, and noise-to-harmonics ratio were measured before the intervention (m0), as well as after 5 minutes (m5), 10 minutes (m10), 15 minutes (m15), and 20 minutes (m20) of intervention.PTP decreased significantly after straw phonation and reached a minimum value at 10 minutes (P 0.001) and remained stable in traditional singing exercises. There were significant differences in fundamental frequency and shimmer from m0 to m15 and m20 in the traditional singing group (P = 0.001, P = 0.001, P = 0.001, and P = 0.002, respectively). No significant changes in acoustic parameters were observed after straw phonation.Both straw phonation exercises and traditional singing exercises are effective for voice warm-up. Straw phonation improves the subjects' fatigue resistance and vocal economy, resulting in a reduced PTP, whereas traditional singing exercises focus on technical singing skills, leading to an improvement of acoustic variables.

The effects of nicotine replacement therapy (NRT)-aided smoking cessation on vascular function are not fully clarified. We investigated 100 healthy smokers who were motivated to quit and received NRT for a 3-month period. Vascular endothelial function (measured by reactive hyperemia-peripheral arterial tonometry [RH-PAT]), arterial stiffness (measured by augmentation index [AI] and brachial-ankle pulse wave velocity [baPWV]), and systemic inflammation markers (including serum soluble intercellular adhesion molecule-1 [sICAM-1] and interleukin-1β [IL-1β]) were assessed at baseline and 3 and 12 months of follow-up. After 3 months of intervention, endothelial function, arterial stiffness, and inflammatory markers significantly improved (RH-PAT increased, AI and baPWV decreased, sICAM-1 and IL-1β decreased, all P < .05) for the participants who abstained from smoking completely, but for those who did not abstained completely, RH-PAT, AI, baPWV, and IL-1β remained unchanged. At 12 months follow-up, endothelial function (RH-PAT), arterial stiffness (AI and baPWV), and inflammatory markers (sICAM-1 and IL-1β) were further improved in participants who abstained from smoking ( P < .001), while the above parameters deteriorated in continued smokers ( P < .05). In conclusion, vascular dysfunction can be reversible after NRT-aided smoking cessation in healthy smokers and vascular function could be further damaged if they continue smoking.

Some studies have shown a superiority of visual vs. auditory item presentation in the Complex Trial Protocol (CTP), which is a countermeasure-resistant version of the P300-based Concealed Information Test (CIT). But those studies used elaborately- rehearsed autobiographical information as stimuli, instead of incidentally-acquired crime-related information. Thus, the relative superiority of the visual as opposed to the auditory modality in detecting episodic crime-related information is still unknown. The present study also improved on the usual mock crime scenario by adding a mock disposal task between a mock theft and administration of a CTP test to increase stimulus saliency. In this CTP, the probe and the irrelevant items were presented visually or acoustically on alternating trials, while target and non-target stimuli were simultaneously presented in visual and auditory modalities. The results showed that the P300 amplitude differences of probe minus irrelevant items presented in the visual modality were significantly larger compared to the auditory modality, and the detection rate of the guilty participants was also significantly higher for the visual (14/16) versus auditory modality (5/16). These results suggest a superiority of visual vs. auditory presentation when a CTP is used to detect crime-related information in a mock crime scenario.

A number of clinical trials demonstrated that tigecycline was effective and well tolerated in the treatment of patients with various bacterial infections, but few literatures had shown the coagulopathy induced by tigecycline. To address this concern, we performed a retrospective analysis to assess the impact of tigecycline treatment on coagulation parameters in 50 patients with bacterial infections in our hospital (Shandong Provincial Hospital, China). These patients were treated with tigecycline at Shandong Provincial Hospital in 2015-2016 at either a recommended (50 mg q12h) or a higher dose (100 mg q12h). Coagulation parameters, including Fibrinogen (FIB) levels, prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count (PLT) and D-dimer, were evaluated in order to assess the impact of tigecycline treatment in these severely infected patients. What we found was that the plasma fibrinogen (FIB) level was 4.63 ± 1.56 g/L before tigecycline treatment, and decreased to 2.92 ± 1.23 g/L during treatment, which was statistically significant (p < 0.001). The mean values of aPTT and PT were significantly increased from 39.58 ± 8.72 to 44.05 ± 10.45 s (p = 0.002), and from 15.37 ± 1.53 to 16.37 ± 2.64 s (p = 0.004), respectively. This study demonstrates that treatment of tigecycline could reduce FIB, prolong aPTT and PT. In conclusion, we advise that it is necessary for practitioners routinely monitor coagulation level in at-rick patient populations treated with tigecycline.

Linkage disequilibrium and disease-associated variants in the non-coding regions make it difficult to distinguish the truly associated genes from the redundantly associated genes for complex diseases. In this study, we proposed a new conditional gene-based framework called eDESE that leveraged an improved effective chi-squared statistic to control the type I error rates and remove the redundant associations. eDESE initially performed the association analysis by mapping variants to genes according to their physical distance. We further demonstrated that the isoform-level eQTLs could be more powerful than the gene-level eQTLs in the association analysis using a simulation study. Then the eQTL-guided strategies, that is, mapping variants to genes according to their gene/isoform-level variant-gene cis-eQTLs associations, were also integrated with eDESE. We then applied eDESE to predict the potential susceptibility genes of schizophrenia and found that the potential susceptibility genes were enriched with many neuronal or synaptic signaling-related terms in the Gene Ontology knowledgebase and antipsychotics-gene interaction terms in the drug-gene interaction database (DGIdb). More importantly, seven potential susceptibility genes identified by eDESE were the target genes of multiple antipsychotics in DrugBank. Comparing the potential susceptibility genes identified by eDESE and other benchmark approaches (i.e., MAGMA and S-PrediXcan) implied that strategy based on the isoform-level eQTLs could be an important supplement for the other two strategies (physical distance and gene-level eQTLs). We have implemented eDESE in our integrative platform KGGSEE (http://pmglab.top/kggsee/#/) and hope that eDESE can facilitate the prediction of candidate susceptibility genes and isoforms for complex diseases in a multi-tissue context.

The widespread presence of 17 beta-estradiol (E2) in the environment is an emerging problem because it poses a potential threat to human health and aquatic organisms. In this study, a strain of E2 degrading bacteria was isolated from activated sludge. 16s rRNA analysis combined with physiological and biochemical detection confirmed that the bacterium was Ochrobactrum sp. strain FJ1. At an initial E2 concentration of 15 mg L-1, strain FJ1 degraded 98 +/- 1% of E2 after 10 days. Furthermore, when methanol was added as an additional carbon source, the biomass of strain FJ1 increased by 35 +/- 1%, and E2 degradation efficiency was slightly inhibited. Compared with E2 alone when glucose, sodium acetate, and methanol were added as additional carbon sources, biomass decreased by 20 +/- 1, 13 +/- 1 and 35 +/- 1%, respectively. Analysis of the degradation products of E2 by LC/Q-TOF-MS confirmed that the major degradation products of E2 were estrone (E1) and 4,16-OH-E1, which was further degraded by strain FJ1 to several other unknown compounds. Based on SEM and FTIR analysis, the morphology of the bacteria became thicker and the thickness of the cell walls decreased under initial E2 stress, and thereafter E2 was transported into the bacteria primarily via several proteins on the cell surface. Considering the ability and efficiency of Ochrobactrum sp. strain FJ1 to degrade high E2 content, the strain could provide a new bioremediation technology for the effective biodegradation of E2. Finally, a potential bioremediation pathway of E2 by Ochrobactrum sp. strain FJ1 was proposed. Refereed/Peer-reviewed

L-carnitine is an amino acid derivative that is thought to be helpful for treating renal anemia in hemodialysis patients. However, the mechanism remains to be fully elucidated.A literature search was performed on PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) and conduct a meta-analysis for investigating the effect of L-carnitine in the treatment of renal anemia in participants receiving hemodialysis.A total of 18 eligible trials with 1090 participants were included in this study. L-carnitine can significantly increase plasma free L-carnitine levels (mean difference [MD]: 140.53, 95% confidence interval [CI] 102.22-178.85; P 0.00001), decrease the erythropoietin responsiveness index (ERI; MD: -2.72, 95% CI -3.20 to -2.24; P 0.00001) and the required erythropoiesis-stimulating agent (ESA) doses (MD: -1.70, 95% CI -2.04 to -1.36; P 0.00001). However, the use of L-carnitine was not associated with a higher hemoglobin level (MD: 0.18, 95% CI -0.20 to 0.55; P = 0.35) and hematocrit level (MD: 1.07, 95% CI -0.73 to 2.87; P = 0.24). In subgroup analyses, the effects of L-carnitine supplementation on renal anemia in patients on hemodialysis were independent of the treatment duration and intervention routes.The present meta-analysis indicated that L-carnitine therapy significantly increased plasma L-carnitine concentrations, improved the response to ESA, decreased the required ESA doses in patients receiving hemodialysis, and maintained hemoglobin and hematocrit levels. L-carnitine supplementation should be supported in hemodialysis patients. However, the relationship between L-carnitine treatment and long-term outcomes is still unclear. Further high-quality RCTs are needed to verify our findings.

ObjectiveTo examine the associations of rotating night shift work with hyperhomocysteinaemia (HHcy) odds by different exposure metrics.DesignCross-sectional study.SettingOccupational physical examination centre for steel production workers, Tangshan, China.ParticipantsA total of 6846 steelworkers, aged 22–60 years, from the baseline survey of a Chinese occupational cohort.Primary and secondary outcome measuresDifferent exposure metrics of night shift work, including current shift status, duration of night shifts (years), cumulative number of night shifts (nights), cumulative length of night shifts (hours), average frequency of night shifts (nights/month), average length of night shifts (hours/night) and percentage of hours on night shifts, were used to examine the effects of past and current night shift work on HHcy odds. The total homocysteine concentration in the plasma above 15 µmol/L was defined as HHcy.ResultsCompared with those who never worked night shifts, current night shift workers had elevated odds of HHcy (OR 1.23, 95% CI 1.06 to 1.44). Considering a person’s lifetime work schedule and compared with individuals who never worked night shifts, duration of night shifts >28 years (OR 1.35, 95% CI 1.12 to 1.61), average frequency of night shifts >7 nights/month (OR 1.25, 95% CI 1.07 to 1.47) and percentage of hours on night shifts >30% (OR 1.23, 95% CI 1.05 to 1.43) were associated with higher HHcy odds. The duration of night shifts >20 years and the average frequency of night shifts >7 nights/month could significantly increase the odds of HHcy regardless of whether the average length of night shifts was greater than 8 hours/night. After stratification by sex, no significant association was found in female workers between different exposure metrics of night shift work and HHcy.ConclusionsLong duration and high frequency of night shift work are associated with higher HHcy odds among male steelworkers.

As the rate of percutaneous coronary intervention increases, in-stent restenosis (ISR) has become a burden. Random forest (RF) could be superior to logistic regression (LR) for predicting ISR due to its robustness. We developed an RF model and compared its performance with the LR one for predicting ISR. We retrospectively included 1501 patients (age: 64.0 ± 10.3; male: 76.7%; ISR events: 279) who underwent coronary angiography at 9 to 18 months after implantation of 2nd generation drug-eluting stents. The data were randomly split into a pair of train and test datasets for model development and validation with 50 repeats. The predictive performance was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC). The RF models predicted ISR with larger AUC-ROCs of 0.829 ± 0.025 compared to 0.784 ± 0.027 of the LR models. The difference was statistically significant in 29 of the 50 repeats. The RF and LR models had similar sensitivity using the same cutoff threshold, but the specificity was significantly higher in the RF models, reducing 25% of the false positives. By removing the high leverage outliers, the LR models had comparable AUC-ROC to the RF models. Compared to the LR, the RF was more robust and significantly improved the performance for predicting ISR. It could cost-effectively identify patients with high ISR risk and help the clinical decision of coronary stenting.

Background Although dozens of studies have investigated the relationship between the content of serum cystatin C (Cys-C) and diabetic nephropathy (DN), the results are still controversial. Hence, This study aims to explore the accuracy of serum Cys-C for diagnosing DN by meta-analysis. Methods The studies about serum Cys-C diagnosing DN were searched from six online databases from inception to September 22, 2020. The data were processed by Stata 15.0 statistic software. The corresponding diagnostic effect sizes, such as sensitivity and specificity, were obtained. We drew a summary receiver operating characteristic (SROC) curve. We assess the risk of literature bias was following the QUADAS-2 guidelines. Results Twenty-six published studies were identified. The results showed a pooled sensitivity of 0.86 (95% confidence interval (CI): 0.82–0.90), specificity of 0.89 (95%CI: 0.85–0.92), positive likelihood ratio of 7.59 (95%CI: 5.66–10.19), negative likelihood ratio of 0.16 (95%CI: 0.12–0.21), and diagnostic odds ratio of 48.03 (95%CI: 30.64–75.29). The area under the SROC curve was given a value of 0.94 (95%CI: 0.91–0.96). Conclusion Serum cystatin C has an excellent diagnostic value with good sensitivity and specificity for diabetic nephropathy.

Background: A number of recent studies have investigated the optimal dosage and timing of dexamethasone in total hip arthroplasty (THA) but have inconsistent findings. Therefore, we designed the randomized controlled research to look for the optimal intravenous dexamethasone dose for the treatment of early postoperative pain after the THA. Methods: The Declaration of Helsinki principles was followed and the Consolidated Standards of Reporting Trials guidelines for randomized controlled trials was adhered in this study. The First Medical Center in People's Liberation Army General Hospital approved the study (2020-089). After written informed consent was obtained, patients aged between 18 and 80 years with Physical Status I to III of American Society of Anesthesiologists, scheduled for primary unilateral THA, were included in this present work. Randomization is the use of a computer-formed list via a secretary, at a ratio of 1:1:1. The major end points were pain scores at 24 hours, 48 hours, and 72 hours after surgery, with visual analog scale (VAS) utilized at rest, and at 45 degrees passive hip flexion. The secondary outcomes involved the total consumption of morphine, opioid-related side effects, hip range of motion, inflammation markers, and the length of hospital stay. Results: We assumed that the patients who received 3 doses of dexamethasone intravenously possessed the best postoperative results compared to those who received 1 or 2 doses of the dexamethasone. Trial registration: This study protocol was registered in Research Registry (researchregistry5864).

Sexual dysfunction (SD) is one of the late complications in survivors after hematopoietic stem cell transplantation (HSCT), and the gonadal hormones might be involved in the pathogenesis of this pathological process. This study aimed to investigate the incidence of SD by questionnaire, to explore the relationship between SD and the comprehensive gonadal hormones in patients post HSCT. We identified 72 survivors of hematological diseases who underwent HSCT. The sociodemographic characteristics and medical histories of participants were ascertained by a modified version of a questionnaire named “PPSAS-HSCT” in our study. Blood samples were regularly assayed for the global gonadal hormones. Forty-four percent of the females and 51% of the males reported a loss of interest in sexual activities. Ninety-two percent (23/25) of females exhibited decreased serum anti-Mullerian hormone (AMH) levels, and 74% (35/47) of males had elevated follicle-stimulating hormone (FSH) levels. The males with a higher level of oestradiol/testosterone (E2/T) had more symptoms of SD after HSCT. Patients with GVHD who received glucocorticoid (GC) therapy exhibited a lower level of testosterone and more serious SD, especially in the female population. SD and abnormal gonadal hormone homeostasis were present in more than half of the survivors after HSCT. Graft-versus-host disease (GVHD) and glucocorticoid treatment were confirmed to have a significant impact on the levels of testosterone among females. A multimodal intervention for the survivors after HSCT and a better consciousness of the medical staff are necessary for improving the quality of life of the recipients.

Among spine metastases of malignant tumors, thoracic spine metastases account for about 70%. Spinal metastases cause spinal instability, compression of nerve structures, and function damage, which has a serious impact on patients' quality of life (QOL). At present, surgery is main choice in the treatment of spinal metastases. However, conventional surgery still has certain limitations. This study explored the surgical strategy of nerve rescue in patients with spinal thoracic metastases and moderate-to-severe spinal cord injury.In this history case-control study, 42 patients received conventional operation were enrolled as control group, while 38 patients who underwent conventional decompression of laminectomy combined with durotomy were selected as observation group. Perioperative data were recorded for comparisons between the two groups. Visual analogue scale (VAS) of pain, QOL, and 36-item short-form health survey (SF-36) were compared before operation and 3, 6, and 12 months after operation. American Spinal Injury Association (ASIA) grade was evaluated before operation and 1 month after. Complications, recurrence rate, and mortality were also recorded.The VAS scores of the observation group at 3, 6, and 12 months after operation were significantly lower than those before the operation. The QOL and SF-36 scores were increased compared with those taken preoperatively (P0.05). The VAS score of the observation group was lower than that of the control group, and the QOL and SF-36 scores were higher than those in the control group (P0.05). The neurological grades of ASIA 3 months after operation in both groups were significantly improved. The improvement in the observation group was greater than that in the control group (P0.05). The incidences of postoperative complications in the control group and observation group were 19.05% (8/42) and 7.89% (3/38), respectively; the recurrence rates of the two groups were 14.29% (6/42) and 5.26% (2/38), respectively; and the mortality rates of the two groups were 26.19% (11/42) and 18.42%, respectively (7/38) (P0.05).Durotomy based on conventional decompression of laminectomy can effectively save nerve function in metastases of the thoracic spine with moderate or severe spinal cord injury, improve QOL, and is thus worthy of being applied in clinic.

As a malignant tumor originating from the lymphoid hematopoietic tissues, lymphoma has an increased incidence in recent years and has ranked among the top ten malignant tumors in the world. But until now, due to the multiple pathological subtypes and the unclear molecular mechanism, it's still difficult to make rapid diagnosis and accurate prognosis assessment for lymphoma patients. Recently, the development of high-throughput gene sequencing technology has provided the possibility to solve these clinical problems. This technology has realized large-scale screening of specific markers for lymphoma at the molecular biology level, followed by discovery of prognostic indicators and biological targets for new drug research. In this paper, we summarize the results of large-scale high-throughput gene sequencing research, and introduce the genetic changes associated with occurrence and prognosis of lymphomas with different pathological subtypes, hoping to further promote the application of this technology in clinical research of lymphoma.

In this study, we established an experimental human corneal stroma model of simulated cornea tissue composed of thin anterior cornea strips layers obtained from small incision lenticular extraction (SMILE) surgery. We investigated the biomechanical effect of ultraviolet-A- riboflavin cross-linking at different depths of corneal stroma model and correlated it with stromal microstructural changes examined by transmission electron microscopy (TEM). Corneal strips were harvested from fresh human corneal lenticules obtained after SMILE surgery. Experimental models (n = 34) were established by superimposing the corneal lenticule strips until their thickness reached close to 500 μm. Corneal cross-linking (CXL) was performed subsequently using standard or accelerated protocol. Elasticity and viscosity were quantified using stress-strain extensometer. TEM was used to visualize the collagen fiber diameter and interfibrillar spacing. The relative change in Young's modulus (rel. ΔE) decreased nonlinearly with increasing stromal depth both in the standard and accelerated groups. Compared to the sham controls, the rel. ΔE in standard and accelerated CXL groups increased significantly in the anterior 400 μm and 275 μm depth, respectively. Also, the relative change in stress (rel. ΔS) was significantly lower after standard and accelerated CXL compared to sham controls. Depth analysis showed similar results for the elastic effect. TEM images showed a small, non-significant increase in fibril diameter. The interfibrillar spacing decreased significantly after standard and accelerated CXL in the anterior-mid stromal region. We noted that the increase of corneal stiffness correlated with decrease in interfibrillar spacing after CXL. The stiffening effect was depth dependent. The effect of accelerated CXL was less in the deep corneal stromal regions compared to standard CXL.

Low-level laser therapy (LLLT) has been promoted for its beneficial effects on tissue healing and pain relief for skin and oral applications. However, there is no corresponding literature reporting on vocal fold wound healing. Our purpose was to assess the potential wound-healing effects of LLLT on primary human vocal fold epithelial cells (VFECs). In this study, normal vocal fold tissue was obtained from a 58-year-old male patient who was diagnosed with postcricoid carcinoma without involvement of the vocal folds and underwent total laryngectomy. Primary VFECs were then cultured. Cells were irradiated at a wavelength of 635 nm with fluences of 1, 4, 8, 12, 16, and 20 J/cm2 (50 mW/cm2), which correspond to irradiation times of 20, 80, 160, 240, 320, and 400 s, respectively. Cell viability of VFECs in response to varying doses of LLLT was investigated by the Cell Counting Kit-8 (CCK-8) method. The most effective irradiation dose was selected to evaluate the cell migration capacity by using the scratch wound-healing assay. Real-time polymerase chain reaction (RT-PCR) was used to detect the gene expression of TGF-β1, TGF-β3, EGF, IL-6, and IL-10. Irradiation with doses of 8 J/cm2 resulted in 4% increases in cell proliferation differing significantly from the control group (p

Objectives The aim of this study was to evaluate the safety and feasibility of total arch repair with open placement of a novel double-branched stent graft for acute Type A aortic dissection (TAAD). Methods We retrospectively analysed the effect of the double-branched stent graft for total aortic arch placement with acute TAAD from December 2013 to February 2015. The effectiveness of the open placement of the double-branched stent graft was estimated by complete thrombus obliteration of the false lumen surrounding it on computed tomography angiography. Follow-up was performed at 6 months postoperatively and annually thereafter. Results The double-branched stent graft was successfully placed into the true lumen of the descending aorta, aortic arch, left subclavian artery and left common carotid artery through the delivery system in 21 patients with acute TAAD. The mean cardiopulmonary bypass time was 210.2 ± 32.4 min, the mean aortic cross-clamp time was 94.9 ± 18.0 min, and the selective cerebral perfusion and deep hypothermia cardiopulmonary arrest time was 27.0 ± 10.4 min. The in-hospital mortality rate was 4.8%. The mean follow-up duration was 38.2 ± 12.5 months. No severe complications related to the surgery or residual dissection occurred during the follow-up. All survivors resumed normal activities. Conclusions The novel double-branched stent graft is proved to be safe and effective for total arch repair with acute TAAD in this study. It would be a new selective method for total arch repair in patients with acute TAAD. Clinical registration number Research on pathogenic risk factors or characteristic features and clinical treatment of aortic dissection in Chinese Population (20120216-4).

The aim of this study was to investigate the efficacy of high- and low-energy radial shock waves combined with physiotherapy for rotator cuff tendinopathy patients.Data from rotator cuff tendinopathy patients received high- or low-energy radial shock waves combined with physiotherapy or physiotherapy alone were collected. The Constant and Murley score and visual analog scale score were collected to assess the effectiveness of treatment in three groups at 4, 8, 12, and 24 weeks.In total, 94 patients were involved for our retrospective study. All groups showed remarkable improvement in the visual analog scale and Constant and Murley score compared to baseline at 24 weeks. The high-energy radial shock waves group had more marked improvement in the Constant and Murley score compared to the physiotherapy group at 4 and 8 weeks and at 4 weeks when compared with low-energy group. Furthermore, high-energy radial shock waves group had superior results on the visual analog scale at 4, 8, and 12 weeks compared to low-energy and physiotherapy groups.This retrospective study supported the usage of high-energy radial shock waves as a supplementary therapy over physiotherapy alone for rotator cuff tendinopathy by relieving the symptoms rapidly and maintaining symptoms at a satisfactory level for 24 weeks. Implications for Rehabilitation High-energy radial shock waves can be a supplemental therapy to physiotherapy for rotator cuff tendinopathy. We recommend the usage of high-energy radial shock waves during the first 5 weeks, at an interval of 7 days, of physiotherapy treatment. High-energy radial shock waves treatment combined with physiotherapy can benefit rotator cuff tendinopathy by relieving symptoms rapidly and maintain these improvements at a satisfactory level for quite a long time.

Objective— Oxidative stress and inflammation play key roles in the development of pulmonary arterial hypertension (PAH). Cyclophilin A (CypA) is secreted in response to oxidative stress and promotes inflammation and cardiovascular disease. Endothelial cell (EC) dysfunction is an early event in the pathogenesis of PAH. We evaluated the role of extracellular CypA in PAH and compared the effects of acetylated CypA (AcK-CypA, increased by oxidative stress) and CypA on EC dysfunction. Approach and Results— In transgenic mice that express high levels of CypA in EC specifically, a PAH phenotype was observed at 3 months including increased right ventricular systolic pressure, α-smooth muscle actin expression in small arterioles, and CD45-positive cells in the lungs. Mechanistic analysis using cultured mouse pulmonary microvascular EC and human pulmonary microvascular EC showed that extracellular CypA and AcK-CypA stimulated EC inflammatory signals: increased VCAM1 (vascular cell adhesion molecule 1) and ICAM1 (intercellular adhesion molecule 1), phosphorylation of p65, and degradation of IkB. Extracellular CypA and AcK-CypA increased EC apoptosis measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, Apo-ONE assay, and caspase 3 cleavage. Oxidative stress stimulated CypA and AcK-CypA secretion, which further promoted EC oxidative stress. AcK-CypA, compared with CypA, stimulated greater increases in apoptosis, inflammation, and oxidative stress. MM284, a specific inhibitor of extracellular CypA, attenuated EC apoptosis induced by CypA and AcK-CypA. Conclusions— EC-derived CypA (especially AcK-CypA) causes PAH by a presumptive mechanism involving increased EC apoptosis, inflammation, and oxidative stress. Our results suggest that inhibiting secreted extracellular CypA is a novel therapeutic approach for PAH.

Constitutive or excessive activation of Toll-like receptor (TLR) signaling pathway can disrupt the body's immune tolerance to autoantigen, thus promoting the development of autoimmune disease. However, the expression profile of TLR signaling pathway in peripheral blood neutrophils in the pathogenesis of microscopic polyangiitis (MPA) remains unclear. Thus, improved understanding of the pathobiology of this disease may aid in the development of therapeutic targets for patients with MPA. In the present study, we assessed the expression of TLR signaling pathway-related genes in peripheral blood neutrophils in patients with MPA. PCR array analysis was performed on 20 patients with MPA and 12 healthy controls. Gene expression profile was performed using the human TLR for autoimmunity and inflammation PCR array of Genecopoeia, containing 84 genes related to TLR signaling pathway and six house-keeping genes. We then used quantitative real-time PCR to validate the array test. The array results identified 13 upregulated genes and 5 genes which were downregulated. The resulting qRT-PCR was consistent with the findings by PCR array. Our results suggest that peripheral blood neutrophils display changes in the expression of TLR signaling pathway-related genes associated with the pathogenesis of microscopic polyangiitis.

We report a case of 41-year-old woman who presented with chest tightness and shortness of breath. Transthoracic echocardiogram (TTE) showed left ventricular (LV) pseudoaneurysm of the inferior wall with preserved LV systolic function. Coronary angiogram was normal. Surgical repair of the pseudoaneurysm with a pericardial patch was performed, and pathological results confirmed rupture of an isolated congenital LV diverticulum, as the most likely etiology.

The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody. Notch1 regulates Dll4 expression by binding to recombining binding protein suppressor of hairless (RBP-J, a transcriptional regulator of Notch) via a highly conserved ankyrin (ANK) repeat domain. We show that GIT1, which also contains an ANK domain, inhibits the Notch1-Dll4 signaling pathway by competing with Notch1 ANK domain for binding to RBP-J in stalk cells.

Background Patients diagnosed as diffuse large B cell lymphoma (DLBCL) with CD5 positive normally have a worse outcome and poorly respond to the regulatory treatment strategy. Results We recently reported differently expressed tRFs and their potential target-genes of tRFs in patients with CD5+ R/R DLBCL. Differently expressed tRFs were detected by Illumina NextSeq instrument and the results were verified by quantitative real-time reverse transcription-PCR. tRF2Cancer database was searched to compared with the results. Further research was performed through bio-informatic analysis including gene ontology (GO) and pathway enrichment analyses, etc. A total of 308 tRFs were identified. Two sequences (AS-tDR-008946, AS-tDR-013492) were chosen for further investigated. Conclusions The results of Bioinformatics analysis revealed that the target genes including NEDD4L and UBA52 and several associated pathways including PI3K/AKT and MAPK/ERK might be involved in the development of CD5+ R/R DLBCL. Our preliminary study on the associated tRFs might provide a valuable measure to explore the pathogenesis and progression of CD5+ R/R DLBCL. Reviewers This article was reviewed by Zhen Qing Ye, Nagarajan Raju and Jin Zhuang Dou.