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In our previous study, serum soluble T-cell immunoglobulin and mucin structure-3 (sTim-3) and galactosin-9 (sGal-9) were found to be associated with renal function after kidney transplantation. However, it is unclear whether these two indicators can predict adverse outcomes after transplantation.Ninety-one recipients of kidney transplantation were enrolled and divided into a stable group and an adverse outcome group (consisting of biopsy-proven rejection, graft loss, death and clinically diagnosed rejection). The expression levels of sTim-3 and sGal-9 before (pre-Tim-3 and pre-Gal-9) and one month after transplantation (post-Tim-3 and post-Gal-9) were measured by ELISA.The level of pre-Tim-3 was significantly higher in the stable group than in the adverse outcome group [median (range), 2275 (840-4236) pg/mL vs. 1589 (353-3094) pg/mL, P = 0.002]. The level of post-Gal-9 was significantly lower in the stable group than in the adverse outcome group [median (range), 4869 (1418-13080) pg/mL vs. 6852: (4128-10760) pg/mL, P = 0.003]. The areas under the curve (AUCs) for pre-Tim-3 and post-Gal-9 were 0.737 (P = 0.002) and 0.751 (P = 0.003), respectively, better than AUC of post-eGFR (0.633) (P = 0.071), according to the receiver operating characteristic (ROC) curve. Through Cox regression analysis, including pre-Tim-3, post-Gal-9, post-eGFR, sex, age, BMI of recipients and donors, pre-Tim-3 and post-Gal-9 were independent risk factors for adverse outcomes after kidney transplantation (P = 0.016, P = 0.033, respectively).Serum sTim-3 and sGal-9 can predict adverse outcomes within two years after kidney transplantation.

Purpose. To evaluate the effectiveness of Janus kinase (JAK) inhibitors for the treatment of patients with autoimmune disease and associated inflammatory ocular diseases. Methods. We identified relevant literature by screening the MEDLINE, PubMed, and Cochrane databases for randomized controlled trials, cohort studies, case controls, and case reports. Results. Seven studies, including 11 patients, were included in the final systematic analysis. Of the 11 patients, there were 5 cases of juvenile idiopathic arthritis- (JIA-) associated uveitis, 1 case of rheumatoid arthritis- (RA-) associated keratitis, 1 case of RA-associated scleritis, 1 case of psoriasis-associated conjunctivitis, 2 cases of noninfectious scleritis, and 1 case of uveitis with suspected autoimmune disease. None of these 11 patients responded adequately to conventional treatments, including biological agents; these were all refractory cases and switched to JAK inhibitor therapy. Irrespective of whether they were suffering from uveitis, scleritis, or other types of ocular inflammation, all 11 patients showed an improvement to JAK inhibitors without significant side effects. Different types of JAK inhibitors might be associated with different responses when used to treat ocular inflammation. Conclusions. JAK inhibitors may represent an alternative treatment option for patients with autoimmune ocular inflammation.

Purpose To investigate the effects of coenzyme Q10 (CoQ10) and transcutaneous electrical acupoint stimulation (TEAS) pretreatment on pregnancy in patients with poor ovarian response (POR). Methods A total of 330 POR patients who were pretreated with CoQ10 or CoQ10 combined with TEAS before their in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles and who were not pretreated were selected and divided into CoQ10 group (group A, n = 110), CoQ10 + TEAS group (group B, n = 110) and control group (group C, n = 110). For patients with 2 or more transfer cycles, only the information of the first cycle was included. Ovarian function, response to gonadotropin (Gn) stimulation, and pregnancy outcomes of the three groups were compared in the IVF/ICSI-ET cycles. Results After pretreatment, basal FSH, total Gn dosage and duration were comparable among the three groups (all p-value > 0.05), basal E2 in group B decreased significantly compared with the control group (p = 0.022). Endometrial thickness on the human chorionic gonadotropin (hCG) day, antral follicle counts (AFC), the numbers of oocytes, metaphase II (MII) eggs and excellent embryos in the two pretreatment groups were significantly increased compared with group C (all p-value p = 0.020; p = 0.027; respectively). The embryo implantation rate (IR), clinical pregnancy rate (CPR) and live birth rate (LBR) in group B were significantly higher than those in group C (p = 0.022; p = 0.010; p = 0.019; respectively), but not significantly different from group A. Conclusion CoQ10 alone or in combination with TEAS are effective methods for IVF/ICSI-ET adjuvant therapy, which can significantly improve ovarian reactivity, increase the numbers of retrieved eggs and superior embryos, and improve endometrial receptivity. Adjuvant TEAS on the basis of CoQ10 can significantly enhance pregnancy rates, but CoQ10 alone failed to present such an obvious effect.

Supplemental Digital Content is Available in the Text., The goal of this systematic review was to compare the clear liquid diet and the low-residue diet to determine which is better for bowel preparation before colonoscopy. A literature search for randomized controlled trials on the effects of employing the clear liquid diet and low-residue diets before colonoscopy was conducted in major online English databases (PubMed, Web of Science, and Ovid EMBASE). After the systematic review of all 16 studies, the outcomes including quality of bowel preparation, tolerance, willingness to repeat, and adverse effects were analyzed through meta-analysis. The statistical analysis was performed by using RevMan 5.3 software. No statistically significant difference was observed between the low-residue diet and clear liquid diet groups (odds ratio [95% confidence interval] = 1.19 [0.79, 1.81]; p = .41). There was no statistically significant difference between the Boston Bowel Preparation Scale (standard mean difference [95% confidence interval] =−0.04 [−0.21, −0.14]; p = .68) Ottawa Bowel Preparation Scale (standard mean difference [95% confidence interval] =−0.04 [−0.19, 0.11]; p = .59) scores of the two groups. The quality indicators for colonoscopy of the two groups were not statistically significant. However, patient tolerance to the low-residue diet was higher (odds ratio [95% confidence interval] = 1.86 [1.47, 2.36]; p < .01). More patients in the low-residue diet group were willing to repeat the low-residue diet for bowel preparation (odds ratio [95% confidence interval] = 2.34 [1.72, 3.17]; p < .01). More patients in the clear liquid diet group experienced hunger, nausea, and vomiting. People who employed the low-residue diet before colonoscopy had the same quality of bowel preparation as those with clear liquid diet. Meanwhile, the tolerance of people with low-residue diet was better than people with clear liquid diet, and these people were more willing to repeat the colonoscopy with less adverse events.

Depression is a common psychiatric symptom in patients with Sjögren's syndrome (SS). Prevalence of depression in SS patients is significantly higher than that in the general population. Increasing evidence suggests a crucial role of gut-microbiota-brain axis in depression. In this study, we investigated whether non-obese diabetic (NOD) mice, a widely used animal model of SS, exhibit depression-like phenotypes and abnormal composition of gut microbiota. Eleven-week-old NOD mice spontaneously exhibited SS-related symptoms without pancreatic destruction. NOD mice displayed depression-like behaviors, decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Interestingly, SS-related proinflammatory factors in the submandibular gland (SMG) and autoantibodies (anti-SSA and anti-SSB) in the plasma were correlated with the expression of synaptic proteins in the PFC or depression-like behaviors. In addition, there were correlations between the relative abundance of microbiota and SS-related symptoms (or depression-related phenotypes). These data suggest that SS-related symptoms and abnormal composition of gut microbiota may play a role in depression-like phenotypes in NOD mice through gut-microbiota-brain axis.

Background To develop and validate predictive nomograms for 5-year graft survival in kidney transplant recipients (KTRs) with easily-available laboratory data derived markers and clinical variables within the first year post-transplant. Methods The clinical and routine laboratory data from within the first year post-transplant of 1289 KTRs was collected to generate candidate predictors. Univariate and multivariate Cox analyses and LASSO were conducted to select final predictors. X-tile analysis was applied to identify optimal cutoff values to transform potential continuous factors into category variables and stratify patients. C-index, calibration curve, dynamic time-dependent AUC, decision curve analysis, and Kaplan-Meier curves were used to evaluate models' predictive accuracy and clinical utility. Results Two predictive nomograms were constructed by using 0-6- and 0-12- month laboratory data, and showed good predictive performance with C-indexes of 0.78 and 0.85, respectively, in the training cohort. Calibration curves showed that the prediction probabilities of 5-year graft survival were in concordance with actual observations. Additionally, KTRs could be successfully stratified into three risk groups by nomograms. Conclusions These predictive nomograms combining demographic and 0-6- or 0-12- month markers derived from post-transplant laboratory data could serve as useful tools for early identification of 5-year graft survival probability in individual KTRs.

The clinicopathological implication and prospective molecular mechanisms of miRNA‐145‐5p in the metastasis of prostate cancer (PCa) stand unclear. Herein, it is found that miRNA‐145‐5p expression was remarkably reduced in 131 cases of metastatic PCa than 1371 cases of localised ones, as the standardised mean differences (SMD) was −1.26 and the area under the curve (AUC) was 0.86, based on miRNA‐chip and miRNA‐sequencing datasets. The potential targets of miRNA‐145‐5p in metastatic PCa (n = 414) was achieved from the intersection of miRNA‐145‐5p transfected metastatic PCa cell line data, differential expression of metastatic PCa upregulated genes and online prediction databases. TOP2A was screened as one of the target hub genes by PPI network analysis, which was adversely related to miRNA‐145‐5p expression in both metastatic PCa (r = −0.504) and primary PCa (r = −0.281). Gene‐chip and RNA‐sequencing datasets, as well as IHC performed on clinical PCa samples, showed consistent upregulated expression of TOP2A mRNA and protein in PCa compared with non‐PCa. The expression of TOP2A mRNA was also significantly higher in metastatic than localised PCa with the SMD being 1.72 and the AUC of sROC being 0.91. In summary, miRNA‐145‐5p may participate in PCa metastasis by binding TOP2A and be useful as a biomarker for the detection of metastatic PCa.

The mechanisms of inflammation in bone and joint tissue are complex and involve long non‑coding RNAs (lncRNAs), which play an important role in this process. The aim of the present study was to screen out differentially expressed genes in human osteoblasts stimulated by inflammation, and to further explore the mechanisms underlying inflammatory responses and the functional activity of human osteoblasts through bioinformatics methods and in vitro experiments. For this purpose, MG63 cells were stimulated with various concentrations of lipopolysaccharide (LPS) for different periods of time to construct an optimal inflammatory model and RNA sequencing was then performed on these cells. The levels of nuclear enriched abundant transcript 1 (NEAT1), various inflammatory factors, Nod‑like receptor protein 3 (NLRP3) protein and osteogenesis‑related proteins, as well as the levels of cell apoptosis‑ and cell cycle‑related markers were measured in MG63 cells stimulated with LPS, transfected with NEAT1 overexpression plasmid and treated with bexarotene by western blot analysis, RT‑qPCR, immunofluorescence, FISH, TEM and flow cytometry. There were 427 differentially expressed genes in the LPS‑stimulated MG63 cells, in which NEAT1 was significantly downregulated. LPS upregulated the expression of inflammatory cytokines and NLRP3, inhibited the expression of autophagy‑related and osteogenesis‑related proteins, promoted apoptosis and altered the cell cycle, which was partially inhibited by NEAT1 overexpression and promoted by bexarotene. LPS stimulated inflammation in the MG63 cells and inhibited the retinoid X receptor (RXR)‑α to downregulate the expression of NEAT1 and decrease levels of autophagy, which promoted the activation of NLRP3 and the release of inflammatory factors, and impaired the functional activity of osteoblasts, thus promoting the development of inflammation.

Kidney transplantation is the ideal treatment for end-stage renal disease (ESRD). Chronic antibody-mediated rejection (CAMR) is the main cause of graft failure. Tfh and B cells are key immune cells that play important roles in CAMR. In this study, the populations of different Tfh cell phenotypes and B cell subsets in CAMR were investigated in a total of 36 patients. Based on Banff-2019, 15 patients were diagnosed with CAMR (CAMR group), 11 recipients were diagnosed with recurrent or de novo IgA nephropathy (IgAN group), and 10 patients displayed stable renal function (stable group). The Tfh and B cell subsets were analyzed by flow cytometry. The percentage and absolute number of PD-1

Objective Burnout is common in mental health nurses because of work-related stress. Burnout has a negative impact on nurses' health and work performance. The prevalence of high burnout in mental health nurses has been inconclusive across studies. This meta-analysis aimed to estimate the pooled prevalence of high burnout in mental health nurses in China. Methods Electronic databases (PubMed, EMBASE, PsycINFO, Web of Science, CNKI, WanFang and SinoMed) were independently and systematically searched from their commencement date up to 14 May 2018. Studies that reported the prevalence of any of the 3 burnout dimensions (high Emotional Exhaustion (EE), Depersonalization (DP), and low Personal Accomplishment (PA)) as measured by the Maslach Burnout Inventory (MBI) were included and analyzed using the random-effects model. Results A total of 19 studies were included in this meta-analysis. The pooled prevalence of high EE was 28.1% (95% CI: 20.4–35.8%), DP was 25.4% (18.1–32.6%) and low PA was 39.7% (28.3–51.1%). Subgroup analyses found that short working experience, use of MBI-Human Services Survey (HSS), and younger age had moderating effects on prevalence of high burnout. Conclusions Burnout is common in mental health nurses in China. Considering its negative impact on health and work performance, regular screening, preventive measures and effective interventions should be implemented.

Objective: To study the interaction effects of rs10757278 polymorphisms at 9p21 locus and traditional risk factors on coronary heart disease (CHD) in Xinjiang, China. Methods: This case–control study consecutively enrolled 310 unrelated consecutive CHD patients aged 18–70 years old. All study participants were recruited between January and December 2017 from The Heart Center of The First Affiliated Hospital of Xinjiang Medical University. CHD patients were confirmed by coronary angiography (≥50% diameter stenosis in at least one of the major coronary arteries) according to the American Heart Association criteria for the confirmation of CHD. Healthy subjects were randomly selected from the occupational population, who received physical examination in our hospital and matched to cases on the basis of age (±3 years) and sex, those without medical history of cardiovascular diseases, and 536 subjects were selected as the control group after medical history inquiry, physical examination, cardiac ultrasound, electrocardiogram, and other blood biochemical examinations in the hospital. The occupational stress was evaluated by an effort-reward imbalance questionnaire. An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted. Results: Both the case and the control groups showed significant difference in smoking, drinking, physical activity, hypertension, diabetes mellitus, family history of CHD, and body mass index (BMI) (all P < 0.05); prevalence of CHD was not related to occupational stress. There was no significant difference in occupational stress level between the 2 groups (P > 0.05); Differences in rs10757278 genotype between the case group and the control groups were statistically significant; binary logistic regression analysis was used to evaluate the risk factors of CHD. After adjustment for age and sex, significant increased risk effects for CHD were found to be associated with smoking [odds ratio (OR) = 2.311; 95% confidence interval (CI): 1.04–2.499; P < 0.001], physical exercise (OR = 1.365; 95% CI: 1.137–1.639; P < 0.001), hypertension (OR = 4.627; 95% CI: 2.165–10.764; P < 0.001), family history of CHD (OR = 4.103; 95% CI: 3.169–6.892; P < 0.001), BMI (OR = 2.484; 95% CI: 2.036–3.03; P < 0.001), and GG genotype at rs10757278 (OR = 1.978; 95% CI: 1.413–2.769; P < 0.001); We noted that a significant interaction association between GG genotype at rs10757278 and CHD differs across categories of smoking, hypertension, family history of CHD, and BMI. Conclusion: GG genotype at rs10757278 may be a risk factor for CHD. And there are interaction effects between GG genotype of rs10757278 in region 9p21 gene and traditional risk factors.

Background Tumor-infiltrating immune cells are indispensable to the progression and prognosis of clear cell renal cell carcinoma (ccRCC). Objective The aim of this study was to explore the clinical implications of immune cell infiltrates in ccRCC. Methods The Cancer Genome Atlas (TCGA) database (N= 515) and E-MTAB-1980 cohort of patients (N= 101) were adopted to estimate the prognostic value of immune cell infiltration. Twenty-four types of immune cells were evaluated using single-sample gene set enrichment analysis. Cox regression analyses were conducted to develop an immune risk score. Results Survival analyses revealed that 13 genes significantly associated with the overall survival (OS). Furthermore, multivariate Cox analysis identified an immune risk score on the basis of mast cells, natural killer CD56bright cells, T helper 17 (Th17) cells, and Th2 cells. The immune risk score was associated with OS, with hazard ratios of 2.72 (95% CI 2.17-3.40) and 3.24 (95% CI 1.64-6.44) in TCGA and E-MTAB-1980 datasets, respectively. This immune risk score was significantly correlated with some immunotherapy-related biomarkers. Conclusions We profiled a prognostic signature and established an immune risk score model for ccRCC, which could provide novel predictive markers for patients with ccRCC and an indicator for immunotherapy response measurement.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an “intrinsic” spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. Significance: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion–positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype. See related video: https://vimeo.com/438254885 See related commentary by Szulzewsky and Cimino, p. 904. This article is highlighted in the In This Issue feature, p. 890

Relapse of acute lymphoblastic leukemia (ALL) remains a leading cause of childhood cancer-related death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist at diagnosis. However, the genomic landscape, evolutionary trajectories, and mutational mechanisms driving relapse are incompletely understood. In an analysis of 92 cases of relapsed childhood ALL incorporating multimodal DNA and RNA sequencing, deep digital mutational tracking, and xenografting to formally define clonal structure, we identified 50 significant targets of mutation with distinct patterns of mutational acquisition or enrichment. CREBBP, NOTCH1, and RAS signaling mutations arose from diagnosis subclones, whereas variants in NCOR2, USH2A, and NT5C2 were exclusively observed at relapse. Evolutionary modeling and xenografting demonstrated that relapse-fated clones were minor (50%), major (27%), or multiclonal (18%) at diagnosis. Putative second leukemias, including those with lineage shift, were shown to most commonly represent relapse from an ancestral clone rather than a truly independent second primary leukemia. A subset of leukemias prone to repeated relapse exhibited hypermutation driven by at least three distinct mutational processes, resulting in heightened neoepitope burden and potential vulnerability to immunotherapy. Finally, relapse-driving sequence mutations were detected prior to relapse using droplet digital PCR at levels comparable with orthogonal approaches to monitor levels of measurable residual disease. These results provide a genomic framework to anticipate and circumvent relapse by earlier detection and targeting of relapse-fated clones. Significance: This study defines the landscape of mutations that preexist and arise after commencement of ALL therapy and shows that relapse may be propagated from ancestral, major, or minor clones at initial diagnosis. A subset of cases exhibits hypermutation that results in expression of neoepitopes that may be substrates for immunotherapeutic intervention. See related video: https://vimeo.com/442838617 See related commentary by Ogawa, p. 21. See related article by S. Dobson et al . This article is highlighted in the In This Issue feature, p. 5

OBJECTIVE: To study the efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia. METHODS: A total of 147 children with mild iron-deficiency anemia were enrolled in this prospective study. They were divided into an intermittent iron supplementation group (n=83) and a conventional iron supplementation group (n=64). The levels of hemoglobin were measured before treatment and after 1 and 3 months of treatment. The treat response rate and the incidence rate of adverse drug reactions were compared between the two groups. RESULTS: Both groups had a significant increase in the level of hemoglobin after iron supplementation (P0.05). The incidence rate of adverse drug reactions in the conventional iron supplementation group was significantly higher than that in the intermittent iron supplementation group (25% vs 8%, P

The roles of PD-182 KTRs were enrolled in this study. 45 KTRs were included in the chronic allograft dysfunction (CAD) group, and 37 KTRs were included in the stable recipients group. Among the CAD group, 12 cases of antibody-mediated rejection (ABMR) and 4 cases of T cell-mediated rejection (TCMR) were diagnosed by biopsy. The percentage of CXCR5The expression of CXCR5 on CD3Our results suggested that PD-1

Background RNA editing leads to post-transcriptional variation in protein sequences and has important biological implications. We sought to elucidate the landscape of RNA editing events across pediatric cancers. Methods Using RNA-Seq data mapped by a pipeline designed to minimize mapping ambiguity, we investigated RNA editing in 711 pediatric cancers from the St. Jude/Washington University Pediatric Cancer Genome Project focusing on coding variants which can potentially increase protein sequence diversity. We combined de novo detection using paired tumor DNA-RNA data with analysis of known RNA editing sites. Results We identified 722 unique RNA editing sites in coding regions across pediatric cancers, 70% of which were nonsynonymous recoding variants. Nearly all editing sites represented the canonical A-to-I (n = 706) or C-to-U sites (n = 14). RNA editing was enriched in brain tumors compared to other cancers, including editing of glutamate receptors and ion channels involved in neurotransmitter signaling. RNA editing profiles of each pediatric cancer subtype resembled those of the corresponding normal tissue profiled by the Genotype-Tissue Expression (GTEx) project. Conclusions In this first comprehensive analysis of RNA editing events in pediatric cancer, we found that the RNA editing profile of each cancer subtype is similar to its normal tissue of origin. Tumor-specific RNA editing events were not identified indicating that successful immunotherapeutic targeting of RNA-edited peptides in pediatric cancer should rely on increased antigen presentation on tumor cells compared to normal but not on tumor-specific RNA editing per se.

Bladder cancer (BC) ranks as the ninth most commonly diagnosed cancer worldwide. The presence of a transcription factor (TF) has been uncovered as a significant contributor to the pathophysiological changes of cancers. In present study, we elucidated the expression and clinical significance of Homeobox A11 (HOXA11) in BC for the first time, and originally investigated HOXA11 as a TF. Employing in-house immunohistochemistry (IHC), we incorporated 137 BC and 34 non-BC cases to detect the expression of HOXA11 protein in BC tissues. HOXA11-related RNA-sequencing (RNA-seq) expression and RNA microarrays were collected from public databases, the "sva" and "limma" R packages were implemented to integrate and normalize the RNA-seq data and microarrays separately. Integration expression was carried out to further evaluate the HOXA11 expression by utilizing the standard mean difference (SMD). The expression level of HOXA11 in various BC cell lines was also evaluated. We further systematically analyzed the downstream target genes of HOXA11 in BC by utilizing Chromatin Immunoprecipitation Sequencing (ChIP-seq) profiles, differentially expressed genes (DEGs), and HOXA11-related genes. Modification of histone marks on the promoter region of target genes were also discovered by histone ChIP-seq data. Results of the IHC and RNA-seq revealed the protein and mRNA expression of HOXA11 was significantly decreased in BC tissues compared to non-BC tissues (2.98 ± 1.48 vs. 8.23 ± 2.64; 6.87 ± 1.54 vs. 8.38 ± 1.42). Five platforms significantly revealed the down-regulation of HOXA11 expression in BC (GPL96, GPL570, GPL6102, GPL6884, and GPL13497). A similar decreased trend was discovered in BC tissues in expression integration with the incorporated SMD reaching -0.843 (-1.362 ~ -0.325, p = 0.001) and -1.051 (-1.674 ~ -0.428, p = 0.001). Expression of HOXA11 was down-regulated in most of the BC cell lines. COL1A1 was considered as a final HOXA11 target gene and positively related to HOXA11 with the correlation coefficient as 0.584 (95% CI: 0.371-0.739, p 0.001). HOXA11 regulates COL1A1 expression in BC via H3K27ac modification. The expression of COL1A1 was down-regulated with the SMD reached -0.312 (p 0.001). In conclusion, HOXA11 expression is markedly decreased and might promote the transcription of COL1A1 to inhibit BC.

To investigate the radiological classification, gene-mutation status, and surgical prognosis of synchronous multiple primary lung cancer (sMPLC).From January 2013 to October 2019, 192 consecutive patients with sMPLC were investigated. The clinical, CT, molecular, and pathological features of all patients were analyzed. Furthermore, the prognosis of 89 patients who only underwent surgical resection was evaluated.Among 192 patients, all lesions pathologically confirmed or highly suspected as tumors based on radiological findings were retrospectively analyzed, and the CT findings of sMPLC were classified into three types: (I) all lesions manifested as solid nodules/masses (14.06%, 27/192), (II) all lesions manifested as subsolid nodules/masses (43.23%, 83/192), and (III) tumor lesions manifested as a combination of ≥ 2 of the following patterns: solid nodules/masses, subsolid nodules/masses, cystic airspace, and focal consolidation (42.71%, 82/192). For 252 tumors undergoing epidermal growth factor receptor (EGFR)-mutation testing, the EGFR-mutation rate was higher in subsolid tumors than that in solid tumors (p0.05). Among 19 patients with all tumors undergoing surgery and driver-gene testing, genetic heterogeneity was prevalent among the multiple tumors (63.16%,12/19). The highest clinical stage of non-I, ipsilateral distribution of tumors, and CT classification of I indicated a poor prognosis for patients with sMPLC (all p0.05).Subsolid lesions are the most common presentation of sMPLC. Genetic heterogeneity in driver mutations among sMPLC may be present. Prognosis in patients with sMPLC is determined by the highest clinical TNM stage, distribution, and radiological classification among the multiple tumors.• Synchronous multiple primary lung cancer (sMPLC) has three types of CT findings. • Genetic heterogeneity may be prevalent among the multiple tumors. • Prognosis in patients with sMPLC is associated with the highest clinical TNM stage, distribution, and radiological classification among the multiple tumors.

Despite the apparent improvement in air quality in recent years through a series of effective measures, the concentration of PM

Obesity is associated with a higher risk of depression in children and adolescents. This is a meta-analysis of studies examining depressive symptoms in overweight and obese children and adolescents in China.A systematic literature search was performed independently in both English (PubMed, EMBASE, Web of Science and Medline Complete) and Chinese (China National Knowledge Internet, WANFANG Data and WeiPu VIP) databases from their commencement date to December 31, 2018. The pooled prevalence of depressive symptoms was calculated using a random-effects model. Data analyses were performed with STATA Version 12.0, R Version 3.3.0 and R Studio Version 0.99.903.Twenty-two epidemiological and 18 comparative studies were included in the meta-analysis. The overall prevalence of depressive symptoms was 24.02% (95% CI: 15.92%-33.16%) in obese children and adolescents and 22.61% (95% CI: 14.87%-31.34%) in overweigh children and adolescents. Obese children and adolescents were more likely to suffer from depressive symptoms (OR = 1.877, 95% CI: 1.459-2.415, P 0.001) than their non-obese counterparts. The use of different screening scales for depressive symptoms was significantly associated with the prevalence of depressive symptoms.Depressive symptoms are common in overweight and obese children and adolescents in China. Obese, but not overweight children and adolescents had higher risk of depressive symptoms. In order to lessen the risk of depressive symptoms, regular screening and effective interventions should be implemented to reduce obesity and overweight in this population.

Falls are common in older adults with psychiatric disorders, but the epidemiological findings have been inconsistent. This meta-analysis examined the prevalence of falls in older psychiatric patients and its moderating factors. PubMed, EMBASE, Web of Science and PsycINFO databases were independently searched by three investigators from their inception date to Nov 31, 2017. The random effects meta-analysis was used to synthesize the prevalence of falls, while meta-regression and subgroup analyses were conducted to explore the moderating factors. Sixteen of the 2061 potentially relevant papers met the entry criteria for the meta-analysis. The pooled lifetime prevalence of falls was 17.25% (95% confidence interval: 13.14%-21.35%). Neither univariate and nor multivariate meta-regression analyses revealed any moderating effects of the study region, duration, sample size, and quality on the prevalence of falls (P values > 0.05). Falls in older adults with psychiatric disorders are common.

Objective: To evaluate the effect of transcutaneous electrical acupuncture point stimulation (TEAS) on sperm parameters and the underlying molecular mechanisms. Methods: A total of 121 patients diagnosed with oligozoospermia, asthenozoospermia or oligoasthenozoospermia were randomised into four groups (three treatment groups, one control): the TEAS groups were treated with 2 Hz (n=31), 100 Hz (n=31), or mock stimulation (n=29) at acupuncture points BL23, ST36, CV1 and CV4 for 2 months. The control group (n=30) was provided with lifestyle advice only. Results The changes in total sperm count and motility in the 2 Hz TEAS group were significantly greater than those in the mock group and the control group. The change in neutral α-glucosidase (NAG) and zinc levels in the 2 Hz group were significantly greater than those in the mock group and control group, and the changes in fructose levels of the 2 Hz group were significantly greater than those in the control group. Significant increases in calcium and integrin-binding protein 1 (CIB1) and reduction of cyclin-dependent kinase 1 b (CDK1) were also found after 2 Hz TEAS treatment. Conclusions The present findings suggest that 2 Hz TEAS can improve sperm count and motility in patients with abnormal semen parameters, and is associated with increases in seminal plasma zinc, NAG and fructose. The upregulation of CIB1 and downregulation of CDK1 by TEAS may be associated with its positive effects on sperm motility and count. Trial registration: http://www.chictr.org ; registration no. ChiCTR-TRC-11001775.

To explore the difference of bone augmentation in patients with different bone defects by extraction site preservation.From January 2017 to June 2019, 85 patients with dental implants treated in Hefei Second People's Hospital were enrolled and divided into the experimental group (43 cases) and the control group (42 cases) according to random number table method. Patients in the experimental group received extraction site preservation, while patients in the control group underwent routine tooth extraction. The two groups were further divided into one-wall group (remaining one wall of the alveolar socket after surgery), two-wall group (remaining two walls), three-wall group (remaining three wall), and four-wall group (remaining four walls). Postoperative pain, wound healing, and infection were recorded. Cone-beam CT (CBCT) was performed immediately and 6 months after surgery to detect alveolar bone height, bone width, bone width recovery rate, etc. SPSS 22.0 software package was used for statistical analysis.There was no significant difference in pain between the two groups after 24 hours (P0.05). All implants healed well after 7 days, and no wound infection or bone infection occurred 6 months after operation. There was no significant difference in buccal bone volume of alveolar ridge (BV) and lingual volume (LV) before surgery between the two groups (P0.05). BV and LV in the experimental group increased after treatment, and the increase in one- and two-wall subgroups was significantly higher than that in three- and four-wall subgroups. BV and LV in the control group decreased, the differences between the subgroups were statistically significant (P0.05). BV and LV increased in both groups after operation, but significantly higher in the experimental group than in the control group. The increase in bone height in one- and two-wall subgroups was significantly higher than that in three- and four-wall groups (P0.05). Bone width of all subgroups in the experimental group increased, but decreased in the control group. The increase of bone width in the experimental group was significantly different from the control group(P0.05). In the experimental group, the increase in bone width in one- and two-wall groups was significantly higher than that in three-wall group, and the decrease in bone width in one- and two-wall group in the control group was significantly less than that in three- and four-wall group(P0.05). The average recovery rate of bone width in the experimental group was significantly higher than that in the control group. The average recovery rate of bone width in one- and two-wall group in the experimental group was significantly higher than that in the control group(P0.05), while there was no significant difference in the recovery rate from the control group(P0.05). The change of bone width at 70% of root length in the same group was significantly smaller than that at 50% and 30% of root length (P0.05).Extraction site preservation after tooth extraction can relieve alveolar bone resorption and maintain bone mass in contrast to conventional tooth extraction. The smaller the bone defect, the better the bone mass recovery effect.

Chemokines are majorly involved in inflammatory and immune responses. The interferon-γ-inducible chemokines C-X-C motif chemokines 9 and 10 (CXCL9 and CXCL10) are considerably associated with Th1 cells and monocytes, and their expression levels rapidly increase during the early episodes of renal allograft rejection and various infectious diseases. CXCL13 is one of the most potent B-cell and T follicular helper-cell chemoattractants. The expression of CXCL13 in the presence of infection indicates an important chemotactic activity in multiple infectious diseases. C-C motif chemokine ligand 2 (CCL2) can attract monocytes and macrophages during inflammatory responses. However, there are no studies on the role of these chemokines in posttransplant infection in kidney transplant recipients. In this study, CXCL9, CXCL10, CXCL13, and CCL2 were analyzed using the Bio-Plex suspension array system before transplant and 30 days after transplant. The serum levels of CXCL9 and CXCL13 30 days after kidney transplant were associated with infection within 1 year after transplant (P = .021 and P = .002, respectively). The serum levels of CXCL9 and CXCL13 before surgery and those of CCL2 and CXCL10 before and after surgery were not associated with infection within 1 year after transplant (P > .05). The combination of postoperative day (POD) 30 CXCL9 and postoperative day 30 CXCL13 provided the best results with an area under the curve of 0.721 (95% confidence interval, 0.591–0.852), with a sensitivity of 71.4% and specificity of 68.5% at the optimal cutoff value of 52.72 pg/mL. As important chemokines, CXCL9 and CXCL13 could be used to predict the occurrence of infection after kidney transplant.

Robot surgical system is the most advanced laparoscopic surgery technology, with obvious advantages in urology. Training in robotic surgery is essential for the application of future surgical techniques. A standardized training program should be established for robotic surgery in urology and andrology and form a disciplinary consensus of expert ideas based on the actual conditions of China and successful experience abroad. This article summarizes the development status, standardized training, training curriculum and evaluation tools in robotic surgery at home and abroad, exploring the bridging of the gaps in the training program, prospects, and establishment of a training system for robotic surgery operating standards in urology and andrology in China.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays critical roles in the physiological process of oocyte mature and IVF outcomes of patients with infertility. However, the regulation of BDNF expression in the microenvironment surrounding the oocyte is still unknown. We initially predicted some microRNA (miRNA) candidates targeting bdnf with a series of bioinformatics analysis tools to determine the underlying regulatory mechanisms of BDNF, particularly the effect of miRNAs on BDNF expression. Then, we assessed whether the expression of these 14 selected miRNAs was negatively associated with BDNF expression in follicular fluid (FF) samples obtained from mature (>18 mm) or immature (

To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated., Neoadjuvant chemotherapy is a therapeutic option for the treatment of breast cancer. Here, the authors characterize changes in the gene expression profiles and immune microenvironment in serial breast cancer biopsies taken before, during and after neoadjuvant chemotherapy.

Melanoma is a malignant skin cancer type associated with a high mortality rate, but its treatment is currently not ideal. Both microRNA (miR)-214 and cell adhesion molecule 1 (CADM1) are differentially expressed in melanoma, but their role in this cancer type remains unknown. Therefore, the aim of the present study was to investigate the role of CADM1 and miR-214 in melanoma to identify novel targets for its treatment. The expression levels of CADM1 and miR-214 in cells were detected by reverse transcription-quantitative PCR (RT-qPCR). Moreover, cell viability, migration and invasion were measured by MTT, wound healing and Transwell assays, respectively. In addition, the relative expression levels of epithelial-mesenchymal transition (EMT)-related proteins in cells were detected by RT-qPCR and western blotting. It was found that the expression of CADM1 was inhibited in melanoma cells, while miR-214 expression was increased during melanoma tumorigenesis. Furthermore, miR-214 mimics promoted the viability, migration and invasion of melanoma cells. It was also demonstrated that the downregulation of CADM1 reversed the inhibitory effect of the miR-214 inhibitor in melanoma. Moreover, overexpression of CADM1 inhibited the EMT process in melanoma, while the miR-214 inhibitor suppressed the EMT process. The results also indicated that miR-214 promoted the EMT process by downregulating CADM1, which may represent a novel mechanism for the progression of melanoma.

ObjectivesRelevant guidelines and consensuses for COVID-19 contain recommendations aimed at optimising the management in paediatric wards. The goal of this study was to determine the quality of those recommendations and provide suggestions to hospital managers for the adjustment of existing hospital prevention and control strategies, and also to offer recommendations for further research.DesignA rapid review of the guidelines and consensuses for the management in paediatric wards facing COVID-19.MethodsPubMed, EMBASE, the Cochrane Library, UpToDate, China National Knowledge Infrastructure, the Wanfang database and relevant websites such as medlive.cn, dxy.cn, the National Health and Health Commission and the China Center for Disease Control and Prevention were systematically searched through late May 2020. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was then used to assess the quality of the selected articles and summarise the relevant evidence concerning management in paediatric wards.ResultsA total of 35 articles were included, composed of 3 consensus guidelines, 25 expert consensuses and 7 expert opinions. Of the 35 papers, 24 were from China, 2 from the USA, 1 from Spain, 1 from Brazil, 1 from Saudi Arabia and 6 from multinational cooperative studies. Scores for the six domains of the AGREE II tool (scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence) were 98.57%, 53.57%, 17.92%, 69.62%, 26.96% and 50.35%, respectively. Recommendations for nosocomial infection and control, human resource management as well as management of paediatric patients and their families were summarised.ConclusionsDue to the outbreak of COVID-19, the quality of rapid guidelines and consensuses for the management in paediatric wards affected by COVID-19 is unsatisfactory. In the future, it will be necessary to develop more high-quality guidelines or consensuses for the management in paediatric wards to deal with nosocomial outbreaks in order to fully prepare for emergency medical and health problems.

OBJECTIVE. The purpose of this study was to investigate the correlation between iodine concentration (IC) derived from spectral CT and angiogenesis and the relationships between IC and clinical-pathologic features associated with lung cancer prognosis. SUBJECTS AND METHODS. Sixty patients with lung cancer were enrolled and underwent spectral CT. The IC, IC difference (ICD), and normalized IC (NIC) of tumors were measured in the arterial phase, venous phase (VP), and delayed phase. The microvessel densities (MVDs) of CD34-stained specimens were evaluated. Correlation analysis was performed for IC and MVD. The relationships between the IC index showing the best correlations with MVD and clinical-pathologic findings of pathologic types, histologic differentiation, tumor size, lymph node status, pathologic TNM stage, and intratumoral necrosis were investigated. RESULTS. The mean (± IQR) MVD of all tumors was 42.00 ± 27.50 vessels per field at ×400 magnification, with two MVD distribution types. The MVD of lung cancer correlated positively with the IC, ICD, and NIC on three-phase contrast-enhanced scanning (r range, 0.581-0.800; all p 0.05). CONCLUSION. IC indexes derived from spectral CT, especially the IC in the VP, were useful indicators for evaluating tumor angiogenesis and prognosis.

ObjectiveTo examine the protective effects of appropriate personal protective equipment for frontline healthcare professionals who provided care for patients with coronavirus disease 2019 (covid-19).DesignCross sectional study.SettingFour hospitals in Wuhan, China.Participants420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yat-sen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. These study participants were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with covid-19 and were involved in aerosol generating procedures. 77 healthcare professionals with no exposure history to covid-19 and 80 patients who had recovered from covid-19 were recruited to verify the accuracy of antibody testing.Main outcome measuresCovid-19 related symptoms (fever, cough, and dyspnoea) and evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as a positive test for virus specific nucleic acids in nasopharyngeal swabs, or a positive test for IgM or IgG antibodies in the serum samples.ResultsThe average age of study participants was 35.8 years and 68.1% (286/420) were women. These study participants worked 4-6 hour shifts for an average of 5.4 days a week; they worked an average of 16.2 hours each week in intensive care units. All 420 study participants had direct contact with patients with covid-19 and performed at least one aerosol generating procedure. During the deployment period in Wuhan, none of the study participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARS-CoV-2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%).ConclusionBefore a safe and effective vaccine becomes available, healthcare professionals remain susceptible to covid-19. Despite being at high risk of exposure, study participants were appropriately protected and did not contract infection or develop protective immunity against SARS-CoV-2. Healthcare systems must give priority to the procurement and distribution of personal protective equipment, and provide adequate training to healthcare professionals in its use.

Background Both genetic and methylation analysis have been shown to provide insight into the diagnosis and prognosis of many brain tumors. However, the implication of methylation profiling and its interaction with genetic alterations in pediatric low-grade gliomas (PLGGs) are unclear. Methods We performed a comprehensive analysis of PLGG with long-term clinical follow-up. In total 152 PLGGs were analyzed from a range of pathological subtypes, including 40 gangliogliomas. Complete molecular analysis was compared with genome-wide methylation data and outcome in all patients. For further analysis of specific PLGG groups, including BRAF p.V600E mutant gliomas, we compiled an additional cohort of clinically and genetically defined tumors from 3 large centers. Results Unsupervised hierarchical clustering revealed 5 novel subgroups of PLGG. These were dominated by nonneoplastic factors such as tumor location and lymphocytic infiltration. Midline PLGG clustered together while deep hemispheric lesions differed from lesions in the periphery. Mutations were distributed throughout these location-driven clusters of PLGG. A novel methylation cluster suggesting high lymphocyte infiltration was confirmed pathologically and exhibited worse progression-free survival compared with PLGG harboring similar molecular alterations (P = 0.008; multivariate analysis: P = 0.035). Although the current methylation classifier revealed low confidence in 44% of cases and failed to add information in most PLGG, it was helpful in reclassifying rare cases. The addition of histopathological and molecular information to specific methylation subgroups such as pleomorphic xanthoastrocytoma–like tumors could stratify these tumors into low and high risk (P = 0.0014). Conclusion The PLGG methylome is affected by multiple nonneoplastic factors. Combined molecular and pathological analysis is key to provide additional information when methylation classification is used for PLGG in the clinical setting.

To investigate the long-term clinical value of prostate 125I brachytherapy (BT) combined with maximal androgen blockade (MAB) in the treatment of metastatic prostate cancer (mPCa).We retrospectively analyzed the clinical data on 173 cases of mPCa treated by MAB (n = 126) or BT+MAB (n = 47) from December 2011 to December 2016 and followed up for 6－76 (44.17 ± 19.73) months. We compared the PSA level, prostate volume, IPSS, progression-free survival, and the rates of 3- and 5-year overall survival between the two groups.After treatment, the minimum PSA level was significantly lower in the BT+MAB than in the MAB group ［3.77 ± 4.14］ vs ［5.96 ± 7.01］ ng/ml, P = 0.046) and the time to reach the minimum level was shorter in the former than in the latter (［5.19 ± 2.83］ vs ［6.52 ± 3.34］ mo, P = 0.016). The prostate volume was markedly reduced in both of the groups at 1, 3 and 5 years after treatment as compared with the baseline, even more significantly in the BT+MAB than in the MAB group (P0.01), though with no statistically significant difference between the two groups before treatment (P = 0.307). The IPSS was remarkably decreased in both of the groups at 1 and 3 years (P0.01) but showed no significant difference at 5 years after treatment as compared with the baseline (P0.05) or between the two groups before and after treatment (P0.05). The progression-free survival was obviously longer in the BT+MAB than in the MAB group (［37.29 ± 15.73］ vs ［29.41 ± 14.37］ mo, P = 0.011), and the rates of 3- and 5-year overall survival were higher in the former than in the latter (74.60% and 60.70% vs 62.60% and 51.50%, P = 0.227 and P = 0.356). Kaplan-Meier survival curves showed no statistically significant difference in the overall survival between the two groups (P = 0.105).Both MAB and BT+MAB are effective therapies for mPCa, but the latter can achieve a longer progression-free survival.

To evaluate the clinical effects of debridement and bone grafting with internal fixation via anterior approach in treatment of tuberculosis of lower cervical vertebrae.The clinical data of 15 patients with tuberculosis of lower cervical vertebrae who accepted the treatment of one-stage debridement and bone grafting with internal fixation from June 2010 to December 2018 were retrospectively analyzed. There were 9 males and 6 females, aged from 39 to 72 years with an average of (54.67±10.75) years. The lesion segment was CAll the 15 operations were successful, no neurological or vascular injury occurred during the operation, and all patients were followed up for 18 to 52 months. The clinical symptoms improved significantly during the follow-up period and CT showed good bone grafting fusion. One patient suffered a relapse of the illness 3 years later, but was healed during the follow-up visit by strengthening the anti tuberculosis therapy.For the patients with vertebral destruction and loss of cervical stability, one-stage debridement and bone grafting with internal fixation via anterior approach has definite curative effects. On the basis of standard anti tuberculosis treatment before operation, the long-term standard anti-tuberculosis treatment after operation is the key to healing the tuberculosis of lower cervical vertebrae.

Objective To explore the influence of desmopressin on gonadotropin-induced spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS). Methods A single-center retrospective cohort study was conducted. All patients with PSIS had both gonadotropin and growth hormone (GH) deficiency. Patients were divided into desmopressin and nondesmopressin groups. The desmopressin and nondesmopressin groups were defined by the presence or absence of central diabetes insipidus, which determined whether the patient received desmopressin or not. Results The average age of gonadotropin therapy was 24.3 and 26.1 in the desmopressin and nondesmopressin groups, respectively. The rate of successful spermatogenesis in the 2 groups was 31.58% and 77.27%, respectively. The period for first sperm appearance was 13.62 ± 5.95 and 13.48 ± 6.69 months, respectively. A multivariable Cox proportional hazards model found that the adjusted hazard ratio for desmopressin was 0.260, indicating a “possible” detrimental effect of desmopressin on spermatogenesis. Central diabetes insipidus would be expected to show a similar detrimental effect. The spermatogenesis rate decreased with increased dosage of desmopressin. In the nondesmopressin group, the rate of spermatogenesis was similar between the GH group and the non-GH subgroup. The GH group had higher sperm count and concentration than the non-GH group. Conclusion A minority of patients with PSIS had mild diabetes insipidus and received desmopressin therapy. The spermatogenesis rate decreased with increasing desmopressin dosage. In addition, GH supplementation did not affect the spermatogenesis rate.

Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroups, PFA-1 and PFA-2, and nine minor subtypes were discovered. Transcriptome profiling suggested a distinct histogenesis for PFA-1 and PFA-2, but their clinical parameters were similar. In contrast, PFA subtypes differed with respect to age at diagnosis, gender ratio, outcome, and frequencies of genetic alterations. One subtype, PFA-1c, was enriched for 1q gain and had a relatively poor outcome, while patients with PFA-2c ependymomas showed an overall survival at 5 years of >90%. Unlike other ependymomas, PFA-2c tumors express high levels of OTX2, a potential biomarker for this ependymoma subtype with a good prognosis. We also discovered recurrent mutations among PFA ependymomas. H3 K27M mutations were present in 4.2%, occurring only in PFA-1 tumors, and missense mutations in an uncharacterized gene, CXorf67, were found in 9.4% of PFA ependymomas, but not in other groups. We detected high levels of wildtype or mutant CXorf67 expression in all PFA subtypes except PFA-1f, which is enriched for H3 K27M mutations. PFA ependymomas are characterized by lack of H3 K27 trimethylation (H3 K27-me3), and we tested the hypothesis that CXorf67 binds to PRC2 and can modulate levels of H3 K27-me3. Immunoprecipitation / mass spectrometry detected EZH2, SUZ12, and EED, core components of the PRC2 complex, bound to CXorf67 in the Daoy cell line, which shows high levels of CXorf67 and no expression of H3 K27-me3. Enforced reduction of CXorf67 in Daoy cells restored H3 K27-me3 levels, while enforced expression of CXorf67 in HEK293T and neural stem cells reduced H3 K27-me3 levels. Our data suggest that heterogeneity among PFA ependymomas could have clinicopathologic utility and that CXorf67 may have a functional role in these tumors.

Background: Interleukin 17 (IL-17) plays an important role in the pathogenesis of autoimmune diseases and might be associated with IgA nephropathy (IgAN). This study aimed to investigate the effect of IL-17 on autoimmune pathogenesis in IgA nephropathy. Methods: DAKIKI cells were cultured and stimulated with IL-17 to perform dose-dependent and time-dependent experiments. Cell proliferation was examined by cell counting and the Cell Counting Kit-8 (CCK-8) assay. The IgA concentration and the degree of galactosylation in the supernatant were tested using ELISA and a helix aspersa (HAA) lectin binding assay, respectively. To study the mechanism of O-glycosylation, cells were stimulated with IL-17, lipopolysaccharide (LPS) or 5-azacytidine (5-AZA) + IL-17 for 48 h, and the levels of C1GALT1 and its molecular chaperone Cosmc were measured by western blot and real-time PCR. Results: The cell counting and CCK-8 results suggested that B lymphocyte proliferation increased significantly with increased IL-17 concentration. IL-17 affected the quantity of IgA1 and its glycosylation status. HAA revealed that IL-17 promoted IgA1 underglycosylation. Mechanistically, the expression of C1GALT1 and Cosmc was significantly lower in cells stimulated by IL-17 or LPS than in the 5-AZA + IL-17 or the control group. Conclusions: Our results suggested that IL-17 stimulates B lymphocyte to promote B-cell proliferation, which leads to increased IgA1 production in vitro accompanied by underglycosylation of IgA1. The molecular mechanism for the IgA1 underglycosylation induced by IL-17 was similar to that of LPS; however, 5-AZA inhibited IgA1 underglycosylation. IL-17 might participate in IgAN pathogenesis by influencing the production and glycosylation of IgA1 in B-cells.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factors family. Recent studies indicated that the level of BDNF in follicular fluid is a marker for oocyte quality and infertility. Here, we intend to further investigate the function of BDNF and its signaling pathway in the regulation of endometrial cells proliferation. We found that BDNF is a critical growth factor in endometrial cells. Activation of signal transducer and activator of transcription 3 signaling pathway is required for BNDF-regulated endometrial cell proliferation. Furthermore, BDNF is an effector of estrogen in endometrial cells. Finally, we investigated the different role of Val66Met, a single-nucleotide polymorphism of the BDNF gene, in regulating endometrial cells proliferation. The results showed that BDNFV66M polymorphism is a loss-of-function polymorphism in the regulation of endometrial cells growth. Given the correlation between endometriosis and infertility, it is important to understand the role of BDNF in regulating endometrial cells proliferation and to develop new therapeutic strategies for the treatment of endometriosis-related infertility.

Background Clinical depression (including major depression, dysthymia, and unspecified depression) is common in children and adolescents with obesity and overweight. The objective of this systematic review and meta-analysis was to examine prevalence of clinical depression among overweight and obese children. Methods PubMed, EMBASE, Web of Science, Medline, Cochrane library, and PsycINFO databases were systematically and independently searched by three researchers from the inception dates to April 01, 2019. The fixed-effects model was used to perform meta-analysis. Data analyses were performed with STATA Version 12.0. Results Eleven studies with 69,893 subjects were included; 5 studies examined major depressive disorder (MDD), while the remaining 6 studies examined other types of clinical depression. In the overweight and obese group, the prevalence of clinical depression ranged from 1.7% to 26.7% in obese subjects and from 4.0% to 16.9% in overweight subjects. In studies on MDD, prevalence ranged from 10.1% to 26.7% in obese subjects and from 9.0% to 16.9% in overweight subjects. The odd ratios (ORs) of clinical depression ranged from 0.92 to 4.39 between obese subjects and healthy controls (i.e., normal-weight controls), and ranged from 0.96 to 1.67 between overweight subjects and controls. Compared to healthy controls, obese (OR = 1.851, 95% CI: 1.410–2.429) but not overweight (OR = 1.068, 95% CI: 0.889–1.283) children and adolescents were more likely to have MDD. Conclusion Obese children and adolescents had a significantly higher risk for MDD compared with healthy controls. Considering the negative health outcomes of depression, regular screening and effective treatments should be implemented for obese children and adolescents.

This study aimed to understand the changes and correlation in the long-term trends of polypharmacy and the utilization of health care services in a population over the age of 50 years through the use of a national database. A total of 2813 subjects who participated in surveys in 1999, 2003, and 2007 were selected as the samples. Each subject was followed-up for the period of 9 years. From 1999 to 2007, the proportion of mild and severe polypharmacy cases increased from 41.5% (1999) to 51.3% (2003) and 57.1% (2007), respectively. This study found that the more severe the polypharmacy was, the higher the risk of health care service utilization would be. The Generalized Estimating Equation model of multivariate analysis showed that the incidence rate ratio of medical utilization increased with the severity of polypharmacy, as did the use of advanced medical resources (ie, the number of hospitalizations). In particular, the increase in incidence rate ratio was more significant in 3 aspects: (1) number of pharmacy visits; (2) number of emergency room admissions; and (3) number of hospitalizations. The government should establish policies and guidance for the safe use of medicines to ensure reduced risk for older people.

Background Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed "DNET-like neoplasms of the septum pellucidum." Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series. Methods We collected 20 of these tumors for a comprehensive study of their clinical, radiological, and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n = 22) were also reviewed for comparative purposes. Results The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum/septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). Septal DNET showed a high frequency (~80%) of mutations of platelet derived growth factor receptor A (PDGFRA), and alterations in fibroblast growth factor receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group. Conclusions Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity.

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosisin the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis andTP53, FLT3 or RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases and included recurrent mutations of ALK and NTRK1, the latter of which drives erythroid leukemogenesis sensitive to TRK inhibition.This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this high-risk leukemia. Refereed/Peer-reviewed

MLL rearrangements impact outcome in HOXA -deregulated T-lineage acute lymphoblastic leukemia: a Children’s Oncology Group Study

BACKGROUND Bladder carcinoma (BLCA) is a leading cause of cancer-related deaths worldwide. The aim of this work was to develop an accurate stratification in predicting the prognosis and directing the treatment of BLCA patients based on small nucleolar RNAs (snoRNAs). MATERIAL AND METHODS Expression profiles of snoRNAs were downloaded from the SNORic database. The expression profiles and clinical outcomes of BLCA patients were analyzed. Survival-associated snoRNAs were identified and used to develop a novel risk score classifier. Genes in the whole genome that were significantly correlated with the included prognostic snoRNAs were used for functional enrichment analysis. RESULTS The results showed that age, American Joint Committee on Cancer (AJCC) stage, and tumor status were significantly correlated with overall survival (OS) of BLCA patients. We selected 12 survival-associated snoRNAs to build a prognostic signature. Patients were separated into high- and low-risk groups based on the median value of the risk score. Patients in the high-risk group and low-risk group have distinct clinical outcomes. The AJCC TNM stage showed moderate utility as a prognostic indicator for clinical outcome prediction. Then, clinical parameters and risk scores were entered in multivariate Cox analysis. Notably, the prognostic signature remained an independent significant prognostic risk factor. The pathway analysis suggested that these genes were enriched in several types of cancer and "Focal adhesion" pathways. CONCLUSIONS The prognostic signature defined by expression profiles of 12 survival-associated snoRNAs appears to be an excellent predictor of the clinical outcome of BLCA patients.

Summary Aims To develop and validate a novel score for prediction of 3‐month functional outcome in neurocritically ill patients. Methods The development of the novel score was based on two widely used scores for general critical illnesses (Acute Physiology and Chronic Health Evaluation II, APACHE II; Simplified Acute Physiology Score II, SAPS II) and consideration of the characteristics of neurocritical illness. Data from consecutive patients admitted to neurological ICU (N‐ICU) between January 2013 and June 2016 were used for the validation. The modified Rankin Scale (mRS) was used to evaluate 3‐month functional outcomes. APACHE II scores, SAPS II scores, and our novel scores at 24 hours and 72 hours in N‐ICU were obtained. We compared the prognostic performance of our score with APACHE II and SAPS II. Results We developed a 44‐point scoring system named the INCNS score, and it includes 19 items which were categorized into five parts: inflammation (I), nutrition (N), consciousness (C), neurological function (N), and systemic function (S). We validated the INCNS score with a cohort of 941 N‐ICU patients. The 72‐hours INCNS score achieved an area under the receiver operating characteristic curve (AUC) of 0.828 (95% CI: 0.802‐0.854), and the 24‐hours INCNS score achieved an AUC of 0.788 (95% CI: 0.759‐0.817). The INCNS score exhibited significantly better discriminative and prognostic performance than APACHE II and SAPS II at both 24 hours and 72 hours in N‐ICU. Conclusion We developed an INCNS score with superior predictive power for functional outcome of neurocritically ill patients.

Smoking is common among nursing students worldwide, but the reported prevalence is inconsistent across epidemiological studies. This is a meta-analysis of the prevalence of smoking in nursing students worldwide.Meta-analysis of observational studies.A total of 46 studies were included in this meta-analysis.Electronic databases (PubMed, Medline, PsycINFO, EMBASE and Web of science) were independently and systematically searched by two investigators from their commencement date up to 12 May 2018. Studies that reported the smoking rate of nursing students were included and analyzed using random-effects model.The pooled prevalence of current smoking was 26.6% (95% CI: 22.9-30.4%), while pooled prevalence of previous smoking was 15.5% (95% CI: 11.8-19.3%). Subgroup analyses showed that smoking rate was higher in male compared with female students (39% vs 25.2%, P .001), while survey time, sample size, age, study design and academic year did not moderate the smoking rate (all P .05).This meta-analysis confirmed that smoking is common in nursing students. Considering the negative impact of smoking on health, appropriate smoking cessation measures for nursing students should be developed.

Double minute chromosomes are extrachromosomal circular DNA fragments frequently found in brain tumors. To understand their evolution, we characterized the double minutes in paired diagnosis and relapse tumors from a pediatric high-grade glioma and four adult glioblastoma patients. We determined the full structures of the major double minutes using a novel approach combining multiple types of supporting genomic evidence. Among the double minutes identified in the pediatric patient, only one carrying EGFR was maintained at high abundance in both samples, whereas two others were present in only trace amounts at diagnosis but abundant at relapse, and the rest were found either in the relapse sample only or in the diagnosis sample only. For the EGFR-carrying double minutes, we found a secondary somatic deletion in all copies at relapse, after erlotinib treatment. However, the somatic mutation was present at very low frequency at diagnosis, suggesting potential resistance to the EGFR inhibitor. This mutation caused an in-frame RNA transcript to skip exon 16, a novel transcript isoform absent in EST database, as well as about 700 RNA-seq of normal brains that we reviewed. We observed similar patterns involving longitudinal copy number shift of double minutes in another four pairs (diagnosis/relapse) of adult glioblastoma. Overall, in three of five paired tumor samples, we found that although the same oncogenes were amplified at diagnosis and relapse, they were amplified on different double minutes. Our results suggest that double minutes readily evolve, increasing tumor heterogeneity rapidly. Understanding patterns of double minute evolution can shed light on future therapeutic solutions to brain tumors carrying such variants. Electronic supplementary material The online version of this article (10.1007/s00401-018-1912-1) contains supplementary material, which is available to authorized users.