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Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.

Background General anesthetics such as sevoflurane interfere with dendritic development and synaptogenesis, resulting in cognitive impairment. The collapsin response mediator protein2 (CRMP2) plays important roles in dendritic development and synaptic plasticity and its phosphorylation is regulated by cycline dependent kinase-5 (Cdk5) and glycogen synthase kinase-3β (GSK-3β). Here we investigated whether Cdk5/CRMP2 or GSK-3β/CRMP2 pathway is involved in sevoflurane-induced developmental neurotoxicity. Methods Rats at postnatal day 7 (PND7) were i.p. injected with Cdk5 inhibitor roscovitine, GSK-3β inhibitor SB415286 or saline 20 min. before exposure to 2.8% sevoflurane for 4 h. Western-blotting was applied to measure the expression of Cdk5/CRMP2 and GSK-3β/CRMP2 pathway proteins in the hippocampus 6 h after the sevoflurane exposure. When rats grew to adolescence (from PND25), they were tested for open-field and contextual fear conditioning, and then long term potentiation (LTP) from hippocampal slices was recorded, and morphology of pyramidal neuron was examined by Golgi staining and synaptic plasticity-related proteins expression in hippocampus were measured by western-blotting. In another batch of experiment, siRNA-CRMP2 or vehicle control was injected into hippocampus on PND5. Results Sevoflurane activated Cdk5/CRMP2 and GSK-3β/CRMP2 pathways in the hippocampus of neonatal rats, reduced dendritic length, branches and the density of dendritic spine in pyramidal neurons. It also reduced the expressions of PSD-95, drebrin and synaptophysin in hippocampus, impaired memory ability of rats and inhibited LTP in hippocampal slices. All the impairment effects by sevoflurane were attenuated by pretreatment with inhibitor of Cdk5 or GSK-3β. Furthermore, rat transfected with siRNA-CRMP2 eliminated the neuroprotective effects of Cdk5 or GSK-3β blocker in neurobehavioral and LTP tests. Conclusion Cdk5/CRMP2 and GSK-3β/CRMP2 pathways participate in sevoflurane-induced dendritic development abnormalities and cognitive dysfunction in developing rats.

Objective This study aimed to assess the prevalence of developmental venous anomaly (DVA) in patients with thalamic glioma. Furthermore, we explored the association between DVA and some important biomarkers, such as IDH1 mutation, and H3K27M mutation. Patients and Methods Patients who received tumor resection in West China Hospital between August 2009 and October 2017 were enrolled. Propensity score matching was conducted based on a logistic regression model and 1:1 matching for case and control was used to generate a new cohort from patients with meningioma. Chi-square test, t-test, univariate and multivariate analyses were employed to assess the prevalence of DVA in thalamic glioma and meningioma and to identify risk factors associated with DVA. Results Ninety-nine patients with thalamic glioma were enrolled in the current study (male, n = 54; female, n = 45). The mean age was 42.9 ± 15.3 years old. We identified a higher prevalence of DVA in 99 patients with thalamic glioma when compared with 99 patients with meningioma (18.18% vs. 7.07%), which was slightly lower than the prevalence of DVA in glioma reported in previous studies. Furthermore, the distribution of gender, age, and tumor grade in DVA did not reach statistical significance. Chi-square test, univariate and multivariate analyses showed that IDH1 mutation, ATRX mutation, MGMT promoter methylation, p53 mutation, MMP9, EGFR, and Top II positive expression, TERT mutation, and H3K27M mutation were not associated with the development of DVA in thalamic glioma. Conclusion A higher prevalence of DVA was found in thalamic glioma compared with meningioma.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer., Highlights • A cathepsin B-responsive theranostic nanomedicine (glycopolymer-PTX-DOTA-Gd) based on a branched glycopolymer was prepared. • Glycopolymer-PTX-DOTA-Gd can be specifically degradated and release drug at tumor enviornment. • Glycopolymer-PTX-DOTA-Gd enhance the contrast of magnetic resonance imaging (MRI) at tumor sites. • The nanomedicine have good biocompatibility, excellent tumor targeting and anti-tumor efficacy., Graphical abstract Cathepsin B-responsive biodegradable branched glycopolymer-based prodrug was designed and prepared as theranostic nanomedicine for cancer treatments, resulting in significantly enhanced therapeutic indexes and strengthened contrast of magnetic resonance imaging (MRI) at tumor sites.Image 1

Objective Given the rarity of patients with pineal glioblastoma (GBM), clinical characteristics, treatment, and prognostic factors are not well characterized. This study aimed to investigate these characteristics and identify the prognostic factors of overall survival (OS). Methods A retrospective analysis of newly diagnosed patients with pineal GBM, including our 3 cases and an additional 44 cases from published articles, was conducted. Survival analysis was performed by Kaplan-Meier analysis and Cox regression analysis was used to determine the prognostic factors. Results A total of 47 patients (28 males and 19 females) were enrolled, with a median age of 46 years (range, 5–74 years). Forty-four patients (90.9%) had preoperative obstructive hydrocephalus. Among 38 patients, 21 (55.3%) had distal leptomeningeal dissemination. Forty-five patients (95.7%) had resection/biopsy, 6 of whom had gross total resection, 22 had subtotal resection, 7 had partial resection, and 10 had biopsy. Adjuvant therapy included radiotherapy in 36 patients and chemotherapy in 27 patients. The median OS was 10.0 months. The 6-month, 1-year, and 2-year survival was 68.0%, 42.6%, and 17.0%, respectively. Cox regression analysis showed that patients receiving biopsy (P = 0.042) or chemotherapy (P = 0.029) had the better OS and these were regarded as independent prognostic factors. Further survival analysis showed that chemoradiotherapy had better survival benefit than other regimens. Conclusions In this study, we summarized the characteristics of patients with pineal GBM and showed the correlation between clinical characteristics and prognosis. This study may give readers a deep understanding of these rare GBMs and provide some references for future management.

Intrauterine adhesion is a major cause of menstrual irregularities, infertility, and recurrent pregnancy losses and the progress towards its amelioration and therapy is slow and unsatisfactory. We aim to summarize and evaluate the current treatment progress and research methods for intrauterine adhesion. We conducted literature review in January 2020 by searching articles at PubMed on prevention and treatment, pathogenesis, the repair of other tissues/organs, cell plasticity, and the stem cell–related therapies for intrauterine adhesion. A total of 110 articles were selected for review. Uterine cell heterogeneity, expression profile, and cell-cell interaction were investigated based on scRNA-seq of uterus provided by Human Cell Landscape (HCL) project. Previous knowledge on intrauterine adhesion (IUA) pathogenesis was mostly derived from correlation studies by differentially expressed genes between endometrial tissue of intrauterine adhesion patients/animal models and normal endometrial tissue. Although the TGF-β1/SMAD pathway was suggested as the key driver for IUA pathogenesis, uterine cell heterogeneity and distinct expression profile among different cell types highlighted the importance of single-cell investigations. Cell-cell interaction in the uterus revealed the central hub of endothelial cells interacting with other cells, with endothelial cells in endothelial to mesenchymal transition and fibroblasts as the strongest interaction partners. The potential of stem cell–related therapies appeared promising, yet suffers from largely animal studies and nonstandard study design. The need to dissect the roles of endometrial cells, endothelial cells, and fibroblasts and their interaction is evident in order to elucidate the molecular and cellular mechanisms in both intrauterine adhesion pathogenesis and treatment.

To evaluate the incidence and types of chromosomal abnormalities in pregnancy loss and aborted fetuses with anomaly and compare the performance of subtelomeric MLPA and chromosomal microarray analysis (CMA) in these specimens. Samples were collected from spontaneous miscarriages, stillbirths and aborted fetuses with anomaly between January 2015 and April 2019. Chromosomal abnormalities were detected using subtelomeric MLPA and CMA. Among the 172 miscarriage samples, CMA detected pathogenic chromosomal abnormalities in 88 cases. MLPA could identified all aneuploidies and most pathogenic CNVs, missing all polyploidies; Of the 30 stillbirths, one pathogenic CNV and two VOUS were identified by CMA, all of which were missed from MLPA; Of the 135 aborted fetuses with anomaly, CMA identified pathogenic chromosomal abnormalities in 32 fetuses (23.7%); 18.95% in fetuses with isolated, and 35% in fetuses with multiple anomalies. MLPA can identify all aneuploidies but missing most pathogenic CNVs. Our systematical comparison of subtelomeric MLPA and CMA for chromosomal analysis of tissue from pregnancy loss and aborted fetuses with anomaly is useful for assessing clinical utility of these techniques. MLPA screening, coupled with CMA analysis, is a cost-effective approach to detect chromosomal abnormalities in miscarriage and anomalous fetuses. However, MLPA might not be appropriate for chromosome analysis in stillbirth without structural anomaly; further research with more samples is needed.

Sorafenib is the first‑line treatment for advanced hepatocellular carcinoma (HCC). Since many HCC patients experience drug resistance, there is an urgent need to discover more effective therapeutic strategies to overcome drug resistance. Long non‑coding RNAs (lncRNAs) play an important role in tumor drug resistance. However, research on the role of lncRNA H19 in sorafenib resistance in HCC is quite limited. In the present study, CCK‑8 assay, RT‑qPCR, EdU staining, immunofluorescence staining, and western blot analysis were used to detect the effect of lncRNA H19 on sorafenib resistance of HCC cells. H19 expression was found to be negatively related to sorafenib sensitivity in HCC cells. Knockdown of lncRNA H19 elevated sorafenib sensitivity by suppressing epithelial‑mesenchymal transition (EMT) in HCC cells. H19 upregulated miR‑675 expression. miR‑675 inhibitor decreased the cell viability in sorafenib‑treated HCC cells, while miR‑675 overexpression had the opposite effect on the treated cells. When the cells were pretreated with miR‑675 mimic, H19 siRNA did not alter the effect of miR‑675 on sorafenib sensitivity. In conclusion, our study provides new clues for further clinical treatment of sorafenib‑resistant liver cancer patients.

Given the rarity in the population with adult thalamic gliomas (ATGs), comprehensive characteristics, treatments and survival outcome are not well characterized. This study was conducted to investigate the comprehensive characteristic and treatment of ATGs and identify the prognostic factors associated with overall survival (OS). A retrospective analysis of newly diagnosed ATGs who underwent surgical resection consecutively was conducted. Survival analysis of OS was performed by Kaplan–Meier analysis. Cox proportional hazard model was used to investigate the possible prognostic factors associated with OS. A total of 102 patients with ATG were enrolled in this study. The median age was 41 years (range 18–68 years). There were 56 (54.9%) males. Sixty-two patients (60.8%) had glioblastoma (GBM). Among these patients, 46 patients (45.1%) had GTR/NTR, 50 patients (49.0%) had STR and 6 patients (5.9%) had PR. Postoperatively, 71.6% of these patients received adjuvant therapy. The median OS was 13.6 months (range 1 week–75 months). COX regression analysis revealed that ATG patients with longer duration of symptoms (p = 0.024), better pre-KPS (p = 0.045), maximal resection (p = 0.013), or lower tumor grade (p = 0.002) had longer OS, and these predictors are considered as independent prognostic factors. Survival analysis showed that ATGs with GTR/NTR plus chemoradiotherapy had significant OS advantage compared with other treatment regimens. This study comprehensively summarized the characteristics, treatments and survival outcomes of ATGs in the largest sample size. Maximal surgical resection can bring survival benefit. Combined-modality therapy regimen of GTR/NTR plus chemoradiotherapy may be better beneficial for OS than other regimens.

Background Glioma is one of the most malignant brain tumors and accounts for the majority of brain cancer related death. Despite progress on mechanistic studies, current understandings of the initiation and progression of glioma are still incomplete. Previous studies demonstrate that Engrailed-2 (EN2), a homeobox-containing transcription factor, is associated with tumorigenesis in a range of cancers heterogeneously, however, the profiles of EN2 expression and its potential functions in gliomas remain unclear. Methods Real-time PCR was used to identify the expression of EN2 in glioma tissues. To study the biological function of EN2 in glioma, we compared the cell viability and proliferation profiles between EN2 overexpressed and control cells using cell counting kit-8 (CCK8) assay, EdU incorporation assay and colony formation assay. Flow cytometry and Hoechst staining assays were performed to investigate the role of EN2 on glioma cell death. Finally, wound healing and transwell assays were carried out to investigate the role of EN2 on glioma cell invasion. Results We identified that EN2 was downregulated in human gliomas compared with paired adjacent normal tissues and negatively associated with glioma malignancy. Elevated EN2 expression inhibits cell proliferation, enhances glioma sensitivity to temozolomide and inhibits migration/invasion of glioma cells. Conclusions Our data identify a novel function of EN2 in glioma suppression and provide potential therapeutic targets for glioma therapy.

Chemotherapy is an important method for treating breast cancer. However, multidrug resistance is one of the major challenges in breast cancer chemotherapy. There is an urgent need to develop novel, effective antitumor strategies that will perfect existing therapeutic regimens. In this study, the double-targeted nanocarrier, Quercetin-3’3-dithiodipropionic acid-Astragalus polysaccharides-Folic acid (QDAF), was successfully synthesized and self-assembled into a neoteric nano-targeted delivery strategy, named nano-pomegranates, and which were utilized to effectively inhibit multidrug resistance in estrogen receptor α (ERα)-positive breast tumor. The outstanding abilities of nano-pomegranates to release the drug in a reducing environment was determined by in vitro release assay. The cellular studies in MCF-7 cells were examined that nano-pomegranates have remarkable efficiencies of enhancing cellular uptake, inhibition and necrosis and apoptosis. In vivo antitumor experiments showed that nano-pomegranates have better anti-tumor effects and lower systemic toxicity than free Cur. In conclusion, nano-pomegranates have great potential in anti-breast cancer treatment.

The central nervous system (CNS) is regarded as an immune privileged environment; however, changes in the neuroimmunology paradigm have led to an increased interest in systematic immunotherapy in lung cancer therapy. The presence of the lymphatic system in the CNS as well as the physiological and biochemical changes in the blood-brain barrier in the tumor microenvironment suggests that immunocytes are fully capable of entering and exiting the CNS. Emerging clinical data suggest that inhibitors of programmed death receptor-1/programmed death ligand 1 (PD-1/PD-L1) can stimulate surrounding T cells and thus have antitumor effects in the CNS. For example, PD-1 antibody (pembrolizumab) monotherapy has displayed a 20-30% encephalic response rate in patients with brain metastases from malignant melanoma or non-small cell lung cancer. Combined application of nivolumab and ipilimumab anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 showed an encephalic response rate of 55% in patients with brain metastases of melanoma. Further evidence is required to verify these response rates and identify the mechanisms of curative effects and drug tolerance. While regional treatments such as whole-brain radiosurgery, stereotactic radiosurgery, and brain surgery remain the mainstream, PD-1/PD-L1 inhibitors display potential decreased neurotoxic effects. To date, five drugs have been approved for use in patients with encephalic metastases of lung carcinoma: the anti-PD-1 drugs, pembrolizumab and nivolumab, and the anti-PD-L1 agents, atezolizumab, durvalumab, and avelumab. In recent years, clinical trials of inhibitors in combination with other drugs to treat brain metastasis have also emerged. This review summarizes the biological principles of PD-1/PD-L1 immunotherapy for brain metastasis of lung cancer, as well as ongoing clinical trials to explore unmet needs.

Objective To summarize and evaluate the evidence of guidelines and systematic reviews (SRs) of nonpharmacological interventions for mild cognitive impairment (MCI) to support the development of future guidelines and clinical decisions for MCI patients. Methods Scottish Intercollegiate Guideline Network (SIGN), National Institute for Health and Clinical Excellence (NICE), American Academy of Neurology (AAN), Registered Nurses Association of Ontario (RNAO), Web of Science, PubMed, Cochrane Library, CNAHL, VIP, China National Knowledge Infrastructure (CNKI), and Wanfang Database were searched for relevant publications, including guidelines and SRs, from January 2014 to March 2019. Two authors independently screened articles, extracted data, and assessed the publications for adherence to the inclusion criteria. Appraisal of Guidelines for Research and Evaluation (AGREE II) was used to assess the quality of the guidelines, and Assessment of Multiple Systematic Reviews (AMSTAR 2) was used to assess the quality of SRs. In addition, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of outcomes. Results Thirty-two articles were retrieved, including 1 guideline and 31 SRs. Fourteen SRs of physical exercise for MCI, six articles describing cognitive interventions, four articles describing acupuncture, and seven articles assessing dietary interventions (including four articles employing a Mediterranean diet, one article using vitamin B supplementation, and two articles assessing the effects of tea, coffee, and caffeine) were included. The quality of the articles was very low for 4 (13%), low for 10 (32%), and moderate for 17 (55%). Conclusions Based on the evidence available to date, nonpharmacological interventions may improve the current cognitive function of persons with MCI. In particular, physical exercise, cognitive interventions, and acupuncture exerted promising effects. However, due to the limited number and quality of the included publications, additional high-quality reviews are needed to further confirm.

Background: Scrub typhus was epidemic in the western Pacific Ocean area and East Asia, scrub typhus epidemic in densely populated areas in southern China. To better understand the association between meteorological variables, Southern Oscillation Index (SOI), and scrub typhus incidence in Guangzhou was benefit to the control and prevention.Methodology/Principal Findings: We collected weekly data for scrub typhus cases and meteorological variables in Guangzhou, and Southern Oscillation Index from 2006 to 2018, and used the distributed lag non-linear models to evaluate the relationships between meteorological variables, SOI and scrub typhus. The median value of each variable was set as the reference. The high-risk occupations were farmer (51.10%), house worker (17.51%), and retiree (6.29%). The non-linear relationships were observed with different lag weeks. For example, when the mean temperature was 27.7°C with1-week lag, the relative risk (RR) was highest as 1.08 (95% CI: 1.01–1.17). The risk was the highest when the relative humidity was 92.0% with 9-week lag, with the RR of 1.10 (95% CI: 1.02–1.19). For aggregate rainfall, the highest RR was 1.06 (95% CI: 1.03–1.11), when it was 83.0 mm with 4-week lag. When the SOI was 19 with 11-week lag, the highest RR was 1.06 (95% CI: 1.01–1.12). Most of the extreme effects of SOI and meteorological factors on scrub typical cases were statistically significant.Conclusion/Significance: The high-risk occupations of scrub typhus in Guangzhou were farmer, house worker, and retiree. Meteorological factors and SOI played an important role in scrub typhus occurrence in Guangzhou. Non-linear relationships were observed in almost all the variables in our study. Approximately, mean temperature, and relative humidity positively correlated to the incidence of scrub typhus, on the contrary to atmospheric pressure and weekly temperature range (WTR). Aggregate rainfall and wind velocity showed an inverse-U curve, whereas the SOI appeared the bimodal distribution. These findings can be helpful to facilitate the development of the early warning system to prevent the scrub typhus.

Objective The objective of this study was to evaluate the effect of empowerment education on depression level and laboratory indicators of patients treated with hemodialysis. Methods We searched databases including Cochrane Library, Web of Science, Embase, PubMed, Chinese Biomedical Literature Database (CBM), Chinese Academic Journals Full-text Database (CNKI), VIP, and Wanfang. We included all the researches about the application of empowerment education in patients treated with hemodialysis. We used RevMan 5.3 to analyze the data after assessing the quality of researches. Results We included 10 studies eventually. The results of meta-analysis showed that the self-efficacy [MD = 1.10, 95% confidence interval (CI; 0.71, 1.48), P < 0.01], depression [MD = -6.94, 95% CI (-8.53, -5.34), P < 0.01], serum creatinine [Scr; MD = -116.46, 95% CI (-171.90, -61.03), P < 0.01], albumin [Alb; MD = 2.93, 95% CI (2.00, 3.86), P < 0.01], and blood urea nitrogen [BUN; MD = -0.95, 95% CI (-1.89, -0.01), P = 0.05] in the empowerment education group had significantly statistical difference compared with those in the usual education group. However, there was no significant difference in hemoglobin [Hb; MD = 3.03, 95% CI (-0.64, 6.70), P = 0.11] between two groups. Conclusions Empowerment education can improve the self-efficacy in patients treated with hemodialysis, relieve depression, and improve Scr, Alb, and BUN. However, there is no significant improvement in Hb; it needs further exploration in clinical practice.

Objectives Avian influenza viruses (AIVs) poise significant risk to human health and the poultry industry. We evaluated the transmission risk along the poultry supply chain. Methods During October 2015 and July 2016, four rounds of cross-sectional surveys were performed to characterize AIV spread in farms, transport vehicles, slaughterhouses, wholesale and retail live poultry markets (LPMs). Poultry cloacal and oral swabs, environmental swabs, bioaerosol samples and human sera were collected. Poultry and environmental samples were tested for AIVs by rRT-PCR, further subtyped by next generation sequencing. Previous human H9N2 infections were identified by hemagglutination inhibition and microneutralization tests. Logistic regression was fitted to compare AIV transmission risk in different settings. Results AIVs was detected in 23.9% (424/1771) of the poultry and environmental samples. AIV detection rates in farms, transport vehicles, wholesale and retail LPMs were 4.5%, 11.1%, 30.3% and 51.2%, respectively. 5.2%, 8.3% and 12.8% of the poultry workers were seropositive in farms, wholesale and retail LPMs, respectively. The regression analysis showed that virus detection and transmission risk to human increased progressively along the poultry supply chain. Conclusions Strengthening control measures at every level along the poultry supply chain, using a one health approach, is crucial to control AIV circulation.

The present study was performed to investigate the prognostic role of the preoperative neutrophil/lymphocyte ratio (NLR) in elderly patients with high-grade glioma.We collected the data from elderly patients (age ≥65 years) who had been diagnosed with high-grade glioma in our hospital from December 2014 to January 2018. The preoperative NLR was evaluated in univariate and multivariate models to examine their effect on overall survival (OS).The study included 135 elderly patients (World Health Organization grade III, n = 22; grade IV, n = 113) with a mean age 70.61 ± 4.60 years. The mean NLR was 3.98 ± 3.28. The optimal NLR cutoff for predicting OS was 3. Of the 135 patients, 65 (48.1%) had a baseline NLR of ≥3 and 70 (51.9%) a baseline NLR3. For patients with an NLR of ≥3 and NLR3, the mean OS was 9.6 months and 17.1 months, respectively. The results showed that age, gender, tumor location, preoperative Karnofsky performance scale score, extent of resection (EOR), and postoperative adjuvant therapy were not associated with the NLR. The tumor grade, neutrophil count, and lymphocyte count were significantly associated with the NLR (P0.001). On univariate analysis, tumor grade, preoperative Karnofsky performance scale score ≥80, EOR, frontal tumor, adjuvant radiotherapy plus temozolomide, NLR of ≥3, and lymphocyte count of ≥1.6 × 10A high NLR was an unfavorable predictor of prognosis for elderly patients with high-grade glioma.

Objective Nurse shortage is a critical problem for global healthcare services. It impacts the quality of clinical care. Work engagement is the core competence of hospitals, which indicates employee's positive attitude toward organization and work. This study aimed to explore the relationships among calling, organizational commitment, and work engagement. Methods A cross-sectional study was designed, and 320 nurses from tertiary hospitals in China completed the questionnaires that included demographic information, calling scale, employee engagement scale, and organizational commitment scale. Pearson correlation was performed to test the correlations among calling, organizational commitment, and work engagement. Stepwise regression analyses were performed to explore the mediating role of organizational commitment. The bootstrap method was employed to confirm the mediating effect. Results Nurses’ work engagement score was at the medium degree, whereas calling and organizational commitment were in the medium to high level. The results revealed that calling, organizational commitment, work engagement, and each dimension were positively correlated with one another (r = 0.145–0.922, P, Highlights • Calling and organizational commitment have positive effects on work engagement. • Organizational commitment partially mediates the relationship between work engagement and calling. • Future career development programs for Chinese nurses should emphasize not only on work engagement but also on calling and organizational commitment.

Purpose This study screened serum proteins to identify potential biomarkers for childhood B-cell and T-cell acute lymphoblastic leukemia (ALL). Patients and methods Serum collected from 20 newly diagnosed B-cell ALL, 20 T-cell ALL and 20 healthy children. The peptides from these samples were subjected to iTRAQ. Differentially expressed proteins (DEPs) were further validated by ELISA in 24 B-ALL, 24 T-ALL, and 24 healthy children. Results Bioinformatics analysis revealed several pathways, including atherosclerosis signaling, interleukin signaling and production in macrophages and clathrin-mediated endocytosis signaling, that were closely related to childhood T-cell ALL. Furthermore, four selected proteins, namely LRG1, S100A8, SPARC and sL-selectin, were verified by ELISA. These results were consistent with the results of the proteomics analysis. Conclusion Serum S100A8 may serve as new diagnostic biomarkers in childhood B-cell ALL and T-cell ALL.

Aims Pseudomyogenic hemangioendothelioma (PHE)/epithelioid sarcoma-like hemangioendothelioma (ES-H) is a rare vascular tumor of intermediate malignancy that commonly occurs in soft tissue of distal extremities of young adults. PHE typically has a multifocal presentation and can involve several tissue planes, including the dermis, subcutis, muscle and bone. Methods and results We present here a unique case of PHE/ESH that arose in the breast as well as a review of the published literature. The initial biopsy was interpreted as a metaplastic carcinoma. However, complete resection largely revealed plump epithelioid cells, and a more spindled cell component was also noted. The cells displayed abundant eosinophilic cytoplasm and central vesicular nuclei arranged in loose fascicles, with a mild, mixed acute and chronic inflammatory infiltrate. Overall, linear membranous staining of CD31 and lack of CD34 expression were highly suggestive of PHE. At the same time, FOSB immunoreactivity was observed, which supported PHE/ESH instead of metaplastic carcinoma. The patient has not shown recurrence in the half year follow up after total mastectomy. Conclusion To our knowledge, this is the first report of breast involvement in this neoplasm. Recognition of its histopathological features and immunohistochemical reactivity will prevent misdiagnosis of breast lesions.

Objectives: To present the prenatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 1q23.3 encompassing PBX1 gene. Case report: A 32-year-old woman (gravida 1, para 0) underwent amniocentesis at 26 weeks' gestation because of constant small fetal kidneys on prenatal ultrasound. Chromosome microarray analysis (CMA) detected a de novo deletion of 1.871 Mb at 1q23.3. The deletion encompassed 2 genes of PBX1 and LMX1A. PBX1 haploinsufficiency had been reported to lead syndromic congenital anomalies of kidney and urinary tract (CAKUT) in humans. Furthermore, at 31 weeks’ gestation, borderline oligohydramnios and restricted fetal dimensions were revealed. Ultimately, the pregnancy was terminated at 32 weeks with a 1500-g female fetus presenting polydactyl of left hand. Conclusions: The shared phenotypes between this case and the previously published prenatal cases demonstrate that loss of function mutation in PBX1 should be suspicious in fetus with bilateral renal hypoplasia, oligohydramnios and intrauterine growth retardation (IUGR). Keywords: PBX1, Renal hypoplasia, Prenatal diagnosis, Chromosome microarray analysis

Biodegradable polymer stents are attracting more attention with their advantages of biocompatibility and biodegradable and dispensing with surgical removal. However, the lower radial force is the main bottle neck of their application. In the present research, poly-L-lactic monofilaments with three different diameters were adopted to produce multi-ply strands and then fabricated into Z-structure stents. The effects of strand parameters on stent radial force were studied. The monofilament, strand and stents were subsequently degraded in vitro for 48 weeks. The thermal properties, morphology change, mass retention and strength retention of samples were recorded to forecast the long-term application effects of the stents. The results of this research provided theory to optimize the processing technique of stents with a textile structure to acquire higher radial force.

In order to investigate essential molecular causes for hearing loss and mutation frequency of deafness-related genes, 1315 newborns who did not pass the Newborn Hearing Screening (NHS) (audio-no-pass) and 1000 random-selected infants were subjected to detection for 101 hotspot mutations in 18 common deafness-related genes. Totally, 23 alleles of 7 deafness genes were detected out. Significant difference (χ2 = 25.320, p = 0.000) existed in causative mutation frequency between audio-no-pass group (81/1315, 6.160%) and random-selected cohort (18/1000, 1.80%). Of the genes detected out, GJB2 gene mutation was with significant difference (χ2 = 75.132, p = 0.000) between audio-no-pass group (417/1315, 31.711%) and random-selected cohort (159/1000, 15.900%); c.109G > A was the most common allele, as well as the only one with significantly different allele frequency (χ2 = 79.327, p = 0.000) between audio-no-pass group (392/1315, 16.84%) and random-selected cohort (140/1000, 7.55%), which suggested c.109G > A mutation was critical for newborns’ hearing loss. This study performed detection for such a large scale of deafness-associated genes and for the first time compared mutations between audio-no-pass and random-recruited neonates, which not only provided more reliable DNA diagnosis result for medical practioners and enhanced clinical care for the newborns, but gave more accurate estimation for mutation frequency.

Aim: To evaluate the accuracy and predictive performance of Bayesian dosing for warfarin in Chinese patients. Materials & methods: Six multiple linear regression algorithms (Wei, Lou, Miao, Huang, Gage and IWPC) and a Bayesian method implemented in Warfarin Dose Calculator were compared with each other. Results: Six multiple linear regression warfarin dosing algorithms had similar predictive ability, except Miao and Lou. The mean prediction error of Bayesian priori and posteriori method were 0.01 mg/day (95% CI: -0.18 to 0.19) and 0.17 mg/day (95% CI: -0.05 to 0.29), respectively, and Bayesian posteriori method demonstrated better performance in all dose ranges. Conclusion: The Bayesian method showed a good potential for warfarin maintenance dose prediction in Chinese patients requiring less than 6 mg/day.

The α+-thal deletion of 3.557 kb (NG_000006.1: g.32745_36301del, -αMAL3.5), involving the entire α2-globin gene, was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. The proband, a compound heterozygote for this mutant gene and the Southeast Asian (- -SEA; NG_000006.1: g.26264_45564del19301) deletion, had a phenotype of Hb H disease [hemoglobin (Hb) 7.6 g/dL, mean corpuscular volume (MCV) 60.0 fL, Hb H (β4) 0.7%, Hb Bart's (γ4) 2.4% and Hb A2 1.1%]; one of her sisters with same genotype showed a similar phenotype. Another two family members, who were carriers of this mutant gene, had a hematological phenotype of a silent α-thal. The 5' and 3' breakpoints of this deletion are located at the Y2 and Y1 boxes, respectively, therefore, it probably originated from an unequal crossover between these two homologous boxes. This mutation constitutes an additional heterogeneous defect causing α-thal in the Chinese population and would be valuable for elucidating the arrangement in the human α-globin gene cluster.

© 2013 IEEE. A high-selectivity low-profile filtering end-fire antenna is proposed using a bandstop filtering (BSF) element integrated into the feedline of the conventional quasi-Yagi antenna. Three transmission zeros (TZs) and six transmission poles (TPs) of the BSF element can be obtained through the odd-even mode equivalent circuit analysis and calculation. With the help of TP and TZ of the BSF element, an additional resonant mode within the operating band and additional radiation null at the upper band edge of the antenna can be obtained, respectively. Consequently, the impedance bandwidth and frequency selectivity of the proposed antenna can be improved compared with the conventional quasi-Yagi antenna. For demonstration, an antenna is fabricated whose measured results exhibit a stable end-fire gain response with two radiation nulls close to two sides of the operation band.

ObjectiveThe outbreak of COVID-19 has major impacts on the psychological health of the public. This study aimed to investigate the anxiety and depression levels of the general population during the rapid progressing stage of COVID-19 pandemic in China and to explore the associated factors.Design and settingA cross-sectional online survey.Participants2651 Chinese people.MeasuresThe Hospital Anxiety and Depression Scale was used to measure their psychological health. A structured questionnaire collected possible associated factors, including sociodemographic characteristics, health information, contact history-related information, experience and perceptions, knowledge and education and adopted precautions. Multiple linear regression was conducted to explore the factors associated with anxiety and depression.ResultsThe mean score of anxiety and depression was 4.35 and 4.38, respectively. The rates of people with anxiety and depressive symptoms (with >7 score in the subscale) were 14.15% and 17.35%, respectively. Participants without political party membership, with contact history of COVID-19, going out or gathering, taking Chinese medicine herbs, being unsatisfied with current precautions, perceiving higher risks of infection, lower knowledge and poorer health presented higher anxiety and depression levels. Moreover, those who were females, married, lived alone and wore mask were more anxious; whereas people who were younger, experienced public health crisis, did not take precautions (regular work-rest, exercise) had higher depression level.ConclusionsDuring the rapid progressing stage of COVID-19 pandemic in China, one-seventh and one-sixth respondents presented anxiety and depression symptoms, respectively. The risk factors for anxiety and depression included the following: without political party membership, with contact history of COVID-19, going out or gathering, wearing masks, taking Chinese medicine herbs, being unsatisfied with current precautions, perceiving higher susceptibility, lower knowledge and poorer health status. Extensive information and psychological support should be provided to improve the mental health of the general population.

Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.

Epithelioid glioblastoma is a new variant of glioblastoma that has been recently recognized in the 2016 WHO classification of brain tumors. Given the rarity of epithelioid glioblastoma, the clinical characteristics, pathological features, radiological findings, and treatment outcomes are still not well characterized. Therefore, we identified eighty-four epithelioid glioblastoma cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 55 male and 29 female patients with a mean age of 33.6 years. Headache (77.3%) was the most common clinical symptom, and other common symptoms included nausea or vomiting (34%), dizziness (20.5%), seizures (13.6%), and limb weakness (13.6%). Most lesions (88.1%) were located in cerebral lobes, especially in the frontal lobe and temporal lobe. One hundred percent of the patients were IDH1 wild-type (75/75) and INI-1 positive (58/58), and 57.3% (47/82) of patients harbored BRAFV600E mutation. The median overall survival (OS) of all patients was 10.5 months. Patients who received chemotherapy (p = 0.006) or radiotherapy (p = 0.022) had a longer survival than patients who did not. In addition, the K-M curve showed that the BRAFV600E mutation status was not associated with survival (p = 0.724). These findings may assist clinicians with better understanding and management of epithelioid glioblastoma.

Aims This study aimed to systematically evaluate the effectiveness of patient decision aids on knowledge, decisional conflict and decisional self-efficacy outcomes in patients with diabetes. Methods A comprehensive database search was performed using the Web of Science, Cochrane Library, PubMed, Embase, PsycINFO (Ovid), CINAHL (EBASCO), CNKI, VIP, Wan Fang Database and the Ottawa Decision Aid Library Inventory (http://decisionaid.ohri.ca/index.html) from inception to 13 October 2019. Two reviewers independently searched databases, screened articles, extracted data and evaluated the risk bias of included studies. Then Rev Man 5.3 software was adopted for statistical analysis. Results Ten articles containing 1,452 people with diabetes were selected. The results of meta-analysis showed that patient decision aids had a positive effect on reducing decisional conflict and improving decisional self-efficacy among patients with type 2 diabetes. Meanwhile, this article also revealed that patient decision aids have beneficial short-term effects on improving knowledge, but there was no significant long-term effect. Conclusion Patient decision aids are capable of becoming support tools to improve shared decision making. Further implementation studies are required to transform patient decision aids tools into clinical practice.

Biapenem is a carbapenem antibiotic. It is excreted predominantly through the kidney as unchanged forms. However, the molecular mechanism of renal excretion of biapenem and potential drug-drug interactions (DDIs) were still unknown. In the present study, the role of organic anion transporters (OAT) 1/3 and organic cation transporters (OCT) 2 in the renal excretion of biapenem, and the potential DDIs between biapenem and six clinical commonly prescribed antibiotics and antiviral drugs that acted as substrates or inhibitors of OAT3 were evaluated in vitro. Further, the effect of probenecid on the pharmacokinetics of biapenem was explored in the rats. We observed that biapenem could not inhibit the transport activities of OAT1 or OCT2, while mildly inhibited OAT3 (IC50 >500 μM). Among the tested antibiotics and antiviral drugs, the relatively high DDI index values (maximal unbound plasma concentration over IC50, Imax,u/IC50) were found for piperacillin, linezolid and benzylpenicillin, which were 2.84, 1.7 and 0.62, respectively. Although probenecid had the highest DDI index (27.1) in vitro, no significant impact of it on the pharmacokinetics of biapenem was observed in the rats. Our results indicated that biapenem was primarily eliminated by the glomerular filtration, while OAT3-mediated renal tubular secretion was a minor route. Biapenem is not a clinically relevant substrate or inhibitor because of its low affinity to OAT3. According to current results, it would be safe to use biapenem with other antibiotics and antiviral drugs that acted as substrates or inhibitors of OAT3.

Neuronal activity increases energy consumption and requires balanced production to maintain neuronal function. How activity is coupled to energy production remains incompletely understood. Here, we report that Rheb regulates mitochondrial tricarboxylic acid cycle flux of acetyl-CoA by activating pyruvate dehydrogenase (PDH) to increase ATP production. Rheb is induced by synaptic activity and lactate and dynamically trafficked to the mitochondrial matrix through its interaction with Tom20. Mitochondria-localized Rheb protein is required for activity-induced PDH activation and ATP production. Cell-type-specific gain- and loss-of-function genetic models for Rheb reveal reciprocal changes in PDH phosphorylation/activity, acetyl-CoA, and ATP that are not evident with genetic or pharmacological manipulations of mTORC1. Mechanistically, Rheb physically associates with PDH phosphatase (PDP), enhancing its activity and association with the catalytic E1α-subunit of PDH to reduce PDH phosphorylation and increase its activity. Findings identify Rheb as a nodal point that balances neuronal activity and neuroenergetics via Rheb-PDH axis.

A 20-year-old female presented with fine motor deficits and visual field defect was admitted to our hospital. CSF tests for autoimmune encephalitis antibodies and onconeuronal antibodies were unremarkable. MRI showed unilateral lesion involving left basal ganglia, external capsule, insula, hippocampus, and amygdala, which was considered to be demyelinating pseudotumor after surgical intervention. The patient's symptoms relieved so she didn't consent to immunotherapy. Two years and a half later our patient reported sudden anosmia. Reexamination by MRI demonstrated a new lesion. We then detected anti-CASPR2 antibodies in the patient's serum and gave her immunotherapy.

Loss-of-function variants in CREBBP or EP300 result in Rubinstein–Taybi syndrome (RSTS). The previously reported cluster of variants in the last part of exon 30 and the beginning of exon 31 of CREBBP, overlapping with the ZNF2 (zinc finger, ZZ-type; residues 1701 to 1744) and ZNF3 (zinc finger, TAZ-type; residues 1764 to 1853) domains, is associated with atypical RSTS. The main features include developmental delay, short stature, microcephaly, distinctive facial features, autistic behavior, feeding difficulties, recurrent upper airway infections, and hearing impairment. Here, we report a 2-year-7-month-old Chinese girl presenting mild cognitive impairments, developmental delay, short stature, recurrent upper airway infections, and facial dysmorphism that resembled the phenotypes of previously reported atypical RSTS patients. The characteristic facial and limb dysmorphism for RSTS was absent in our patient. In addition, our patient exhibited novel phenotypes including attention deficit hyperactivity disorder (ADHD), sleep problem, and abnormal walking posture. Whole-exome sequencing (WES) identified a novel de novo in-frame deletion variant in the beginning of exon 30 of CREBBP (NM_004380:c.4897_4899delTTC, p.Phe1633del) in the HAT domain where no pathogenic variants have been previously reported to be responsible for atypical RSTS. Our case allows us to more accurately define the borders of the CREBBP coding sequence resulting in atypical RSTS, which are extended to the beginning of exon 30 (residue 1633) at the 5′ end of CREBBP in the HAT domain, and reveals novel phenotypes observed in our atypical Chinese RSTS patient.

In the present study, we aimed to compare the effects of icariin (ICA) and bone morphogenetic protein-2 (BMP-2) on osteoblast proliferation and osteogenesis in bone defects. We found that in vitro ICA or BMP-2 treatment is able to increase osteoblast proliferation, which was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Specifically, ICA at a concentration of 30 µg/ml had the strongest ability to promote cell proliferation, which is equivalent with the effect of BMP-2 at a concentration of 50 µg/ml. Furthermore, Western blot and RT-qPCR analyses showed that treatment with ICA (20–30 µg/ml) had similar increase effect with BMP-2 (50 µg/ml) on the protein and mRNA levels of BMP-2, osteoprotegerin (OPG), and alkaline phosphatase (ALP) mRNAs. In addition, the animal model of bone defects was successfully prepared. The in vivo data showed that compared with the control group, highest osteogenesis in the ICA or BMP-2 groups was observed at different observational times. Four weeks after surgery, osteogenesis in the BMP-2 group was slightly higher than that in the ICA group, but there was no significant difference between the two groups until the eighth week. ICA promotes osteoblast proliferation by stimulating the expression of BMP-2 and OPG proteins and upregulating the expression of BMP-2, OPG, and ALP mRNAs. ICA at a certain concentration has the same osteogenic effect as BMP-2. ICA or BMP-2 composite nanomaterials can be used as a framework to guide bone regeneration and promote osteogenesis. In addition, the combined use of hematoxylin-eosin and Goldner’s trichrome staining techniques contributes to acquiring better bone morphometric information about bone defects.

BackgroundCell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China.MethodsA total of 42,924 samples were recruited. The cell-free plasma DNA was directly sequenced. Each of the chromosome aneuploidies of PPV was analyzed. A total of 22 placental samples were acquired, including 14 FP and 8 TP samples. The placental verification of FP NIPT results was performed.ResultsAmong 42,924 samples, 281 (0.65%) positive cases, including 87 of T21, 31 of T18, 22 of T13, and 141 of SCAs were detected. For the detection of T21, the positive predictive value (PPV) was 78.46%, for trisomy 18, 62.96%, for trisomy 13, 10.00%, for SCAs, 47.22% in the total samples. For trisomy 21, the PPV was 86.67%, for trisomy 18, 80.00%, for trisomy 13, 20.00%, for SCAs, 56.52% in advanced maternal age (AMA) women. The PPV of T21 increased with age. For T18, the PPV showed an overall upward trend. For T13 and SCAs, PPV was raised first and then lowered. Placental verification of false positive (FP) NIPT results confirmed confined placental mosaicism(CPM) was the reason for false positives.ConclusionsThis study represents the first time that NIPT has been used as a first-tier screening test for fetal aneuploidies in a pilot city with large clinical samples in China. We propose that NIPT could replace serum biochemistry screening as a first-tier test.

BACKGROUND The present study aimed to assess the association of various age groups with survival in patients with glioblastoma. MATERIAL AND METHODS The Surveillance, Epidemiology, and End Results (SEER) database was used to extracted data on new diagnoses of glioblastoma between 2005 and 2015. Four age models were constructed according to the age at diagnosis. RESULTS A total of 28 734 patients with glioblastoma (16 823 men and 11 911 women) were enrolled in the study. In multivariate analysis, variables including sex, race, tumor, and clinical information were identified as confounding factors to adjust 4 age models. In model 1, ages 39-58, 59-78, and 79+ years were risk factors of survival compared with age 0-18 years. In model 2, ages 18-65, 66-79, and 80+ years were prognostic factors of shorter survival compared with ages 0-17 years. In model 3, ages 45-59, 60-74, and 75+ years were associated with poor prognosis, while ages 18-44 years was associated with favorable clinical outcomes compared with ages 0-17 years. In model 4, ages 18-53, 54-64, and 65+ years were associated with poor prognosis. CONCLUSIONS The differences in prognoses in different age groups of glioblastoma patients suggest that clinicians should incorporate age into routine clinical assessments and develop appropriate treatment strategies.

Background Xp11.22 duplications have been reported to contribute to nonsyndromic intellectual disability (ID). The HUWE1 gene has been identified in all male Xp11.22 duplication patients and is associated with nonsyndromic ID. Currently, few Xp11.22 duplication cases have been reported in the Chinese population, with limited knowledge regarding the role of other genes in this interval. Case presentation We investigated four unrelated Chinese male Xp11.22 duplication patients, performed a comprehensive clinical evaluation for the patients and discussed the role of other genes in this interval. All patients presented with similar clinical features, including ID, speech impairments and motor delay, which were mostly consistent with those of the Xp11.22 duplication described previously. We searched and compared all cases and noted that one of the probands (Family 1) and DECIPHER case 263,219, who carried small overlapping duplications at Xp11.22 that only covered the entire HSD17B10 gene, also suffered from ID, suggesting the important role of HSD17B10 in this interval. Furthermore, three patients (two probands in Families 3 and 4 and DECIPHER case 249,490) had strikingly similar hypogonadism phenotypes, including micropenis, small testes and cryptorchidism, which have not been previously described in Xp11.22 duplication patients. Interestingly, the FGD1 gene was duplicated only in these three patients. Sufficient evidence has suggested that haploinsufficiency of the FGD1 gene causes Aarskog-Scott syndrome, which is characterized by hypogonadism and other abnormalities. Given that, we are the first group to propose that FGD1 may be a potential dosage-sensitive gene responsible for the hypogonadism observed in our patients. Conclusion We reported novel genotypes and phenotypes in Chinese male Xp11.22 duplication patients, and the HSD17B10 and FGD1 genes may be involved.

Background Pathogenic SLC6A1 variants have been reported in patients with myoclonic-atonic epilepsy (MAE). NOTCH1, encoding a member of the Notch family of proteins, is known to be associated with aortic valve disease. The PRIMPOL variant has only been identified in Chinese patients with high myopia. Exome sequencing analysis now allows the simultaneous detection of multiple genetic etiologies for patients with complicated clinical features. However, the presence of three Mendelian disorders in one patient supported by their respective pathogenic variants and clinical phenotypes is very rare. Case presentation Here, we report a 4-year-old Chinese boy who presented with MAE, delayed language, borderline intellectual disability (ID), mildly impaired social skills and attention deficit hyperactivity disorder (ADHD). He also had mild aortic valve stenosis and high myopia. Using whole-exome sequencing (WES), we identified three variants: (1) SLC6A1, NM_003042.4: c.881-883del (p.Phe294del), (2) NOTCH1, NM_017617.5:c.1100-2A > G and (3) PRIMPOL, NM_152683.4:c.265 T > G (p.Tyr89Asp). Parental Sanger sequencing confirmed that SLC6A1 and NOTCH1 variants were de novo, whereas the PRIMPOL variant was inherited from the father who also had high myopia. Furthermore, the PRIMPOL variant was absent from the genomes of the paternal grandparents, and thus was also a de novo event in the family. All three variants are classified as pathogenic. Conclusion The SLC6A1 variant could explain the features of MAE, delayed language, borderline ID, impaired social skills and ADHD in this patient, whereas the features of aortic valve stenosis and high myopia of the patient may be explained by variants in NOTCH1 and PRIMPOL, respectively. This case demonstrated the utility of exome sequencing in uncovering the multiple pathogenic variants in a patient with complicated phenotypes due to the blending of three Mendelian disorders.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a pandemic threat to the whole world. At the same time, influenza virus has been active, with influenza virus and SARS-CoV-2 sharing the same transmission routes. This article aims to alert clinicians of the presence of co-infection with these two viruses and to describe the effect of the measures taken to fight COVID-19 on influenza prevention and control.

Frailty is the most common manifestation of serious health issues in the world, and it is becoming more prevalent worldwide as the aging population grows. Changes that occur in an individual during the aging process have physical, psychological, social, and environmental aspects that make an individual more frail. In China, older people may live in communities for aging individuals. This study aimed to describe the presence and severity of frailty and to analyze influencing factors among this population in China. The Frailty Index 35 (FI-35) scale, which includes 35 items in physical, psychological, social, and environmental domains, was used to investigate frailty. The FI-35 score ranges from zero to one, with a score closer to one indicating greater frailty. Biographical, socioeconomic, and lifestyle factors were measured as potential determinants of frailty. We relied on the November 2017-February 2018 waves of the Chinese cross-sectional study survey that comprised a sample of 513 adults, aged 60 or older, who were living in China. Linear regression was performed to identify factors associated with FI-35 scores. We categorized the determinants of frailty into three models: Model 1: biographical variables; Model 2: biographical and socioeconomic variables; and Model 3: biographical, economic, and lifestyle variables. Frailty scores ranged from 0.00 to 0.89, with a median of 0.31, and the prevalence of frailty was 67.6%. The final model obtained after variable selection included age, minority status, marriage status, income, diet, and exercise. The adjusted R-squared indicated that the analysis explained 13.8% of the variance in frailty scores. Adding household, marriage status, education level, medical insurance, and income as elements in Model 2 explained 25.7%. Adding diet, smoking, drinking, exercise, and hobbies in Model 3 explained 27.9%. The degree of frailty varies considerably among Chinese community-dwelling older people and is partly determined by biographical, socioeconomic, and lifestyle factors. (C) 2020 Elsevier Inc. All rights reserved.

The case‐control study was designed to investigate the genetic effects of interferon‐gamma (IFN‐γ) rs2069727 and rs1861494 polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Blood samples were collected from 108 AS patients and 110 healthy controls. IFN‐γ polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Hardy‐Weinberg equilibrium (HWE) test was performed in control group. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using chi‐square test to evaluate the association between AS susceptibility and IFN‐γ polymorphisms, and the results were adjusted by logistic regressive analysis. The frequency of rs2069727 CC genotype was much higher in cases than that in controls, suggested its significant association with increased AS risk (adjusted OR = 5.899, 95% CI = 1.563‐22.261; P = .009). In addition, C allele also showed close association with increased risk of AS (adjusted OR = 2.052, 95% CI = 1.286‐1.704, P = 0 .003). While the genotype and allele frequencies of IFN‐γ rs1861494 polymorphism were not significantly different between patients and controls (P > 0.05 for all), IFN‐γ rs2069727 polymorphism is significantly associated with increased AS risk in a Chinese Han Population.

Objective To assess the early mortality in pediatric glioma and identify predictors of early mortality, which may provide insight into the therapeutic strategies for children with a high risk of early mortality. Methods We used SEER∗Stat 8.3.5 software to extract data of pediatric glioma from the Surveillance, Epidemiology, and End Results database. Logistical regression to identify the independent factors in predicting early mortality. Results A total of 3035 male and 2741 female patients were enrolled in the present study. The death rates within 1 month and 3 months after diagnosis were 1.32% and 2.44%, respectively. Early mortality decreased significantly during the past 40 years. Our results showed that glioblastoma, anaplastic glioma, and oligodendroglioma were risk factors of early mortality for children diagnosed with glioma, whereas advanced age, gross total resection, radiation, and chemotherapy were associated with decreased early mortality. Conclusions We found a decrease in early mortality during the past 40 years. The death rates within 1 month and 3 months after diagnosis were 1.32% and 2.44%, respectively. Age at diagnosis, histologic subtype, the extent of resection, chemotherapy, and radiation were associated with early mortality in pediatric glioma.

Objective The present study assessed early mortality (within 1 and 3 months) in patients with primary central nervous system lymphoma (PCNSL) and identified the risk factors associated with early mortality. Methods We extracted the data for patients with PCNSL from the Surveillance, Epidemiology, and End Results dataset using the SEER∗Stat, version 8.3.5, software. Results A total of 8091 patients with PCNSL were enrolled in the present study. Of the 8091 patients, 57.94% were men and 42.06% were women. The mean age was 59.50 ± 16.11 years. The rate of death within 1 and 3 months was 10.67% and 29.16%, respectively. During the past 20 years, early mortality declined significantly. The common causes of early death were non-Hodgkin lymphoma and other infectious and parasitic diseases, including human immunodeficiency virus. Our results showed that gender, age at diagnosis, ethnicity, histological subtype, marital status, tumor location, surgery, radiotherapy, and chemotherapy were associated with early mortality within 1 or 3 months. Conclusion The rate of early mortality has declined significantly during the past 20 years. The risk factors for early mortality within 1 or 3 months after a PCNSL diagnosis included advanced age, male gender, black race, frontal lobe location, unmarried, diffuse large B-cell lymphoma, no surgery, no chemotherapy, and no radiotherapy.

A simple multibeam antenna fed by a modified horn beam-forming network (BFN) is realized in substrate integrated waveguide technology. Compared with Rotman lens fed multibeam antenna, such an antenna has the merits of a simple architecture and design process. The modified horn BFN applied here is developed from a traditional horn BFN by adding multiple lateral feeds to perform the beam scanning property. The operation principle, design method, and performance of the multibeam antenna are illustrated sequentially. Fabrication and measurement are conducted to test the consistency between simulation and experiment.

A compact coplanar waveguide (CPW)-fed ultra-wideband (UWB) monopole antenna using embedded E-shaped structure with wireless local area network (WLAN) band-rejection is presented. The introduction of this E-shaped structure working as the radiator can enhance the impedance bandwidth of the UWB antenna without increasing the overall size. For preventing the interference from WLAN system, a pair of L-shaped stubs are connected to the ground of UWB antenna to create the rejected band. The center frequency of this rejected band is about 5.5 GHz with the rejection range of 5.2~5.8 GHz. Good agreement can be observed between the simulated and measured results.

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. Methods: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. Results: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p

Growing evidence from recent studies have revealed that long non-coding RNA (lncRNA) might be a useful prognostic biomarker for glioma; we therefore conducted the current meta-analysis to evaluate prognostic and clinicopathological predictive value of lncRNA expression for glioma patients. Eligible studies were identified through multiple research strategies in PubMed, EMBASE, Web of Science, and Cochrane Library up to May 2017. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized to calculate patient’s survival. Fourteen eligible studies with 1415 patients were ultimately included in this meta-analysis. Our meta-analysis showed a significant association between high lncRNA expression level and OS in glioma patients (HR 2.09, 95% CI 1.68–2.58, P

Dezhi Li,1,* Yu Zhou,1,* Yanhui Liu,2,* Ye Lin,1 Min Yu,1 Xin Lu,1 Bowen Huang,1 Zhonghai Sun,1 Zhixiang Jian,1 Baohua Hou1 1Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Background: Liver kinase B1 (LKB1) is a key regulatory protein of cellular metabolism, proliferation, and polarity. The present study aimed to characterize the expression pattern of LKB1 in pancreatic neuroendocrine tumors (pNETs) and evaluate the relationship between LKB1 expression and prognosis in pNETs. Patients and methods: We retrospectively analyzed the pathologic and clinical data of 71 pNET patients who underwent curative surgical resection in Guangdong General Hospital. LKB1 mRNA and protein levels in tumor tissues and paired nontumor tissues were evaluated in 24 patients by quantitative real-time reverse-transcription polymerase chain reaction and Western blot, respectively. Immunohistochemical expression of LKB1 in tumor tissues was detected in all of the 71 patients, and the immunohistochemical expression level was re-coded in two classes (high versus low/negative) and correlated with clinicopathological parameters and survival outcomes. The association between LKB1 expression and clinicopathological characters was evaluated by chi-square test and Student’s t-test. Kaplan–Meier curves and log-rank test were used to analyze the survival outcomes, including overall survival (OS) and disease-free survival (DFS). Results: Compared to adjacent normal tissues, LKB1 mRNA level and protein expression level in tumor tissues were both increased. The immunostaining of LKB1 was mainly found within the cytoplasm. Overall, 52 of 71 (73.2%) cases were positive for LKB1 protein, which showed either a diffuse staining pattern or a partial staining pattern. Decreased LKB1 expression was correlated with older age (P=0.042), increased Ki-67 index (P=0.004), increased mitotic count (P=0.001), and advanced histologic grade (P=0.001). Moreover, patients with low/negative LKB1 expression had shorter OS and DFS than those with high expression. Conclusion: Our results suggested that LKB1 expression could be a useful prognostic marker for recurrence and survival in pNET patients who had received curative resection. Keywords: pancreatic neuroendocrine tumors, liver kinase B1, LKB1, prognosis

OBJECTIVE The aim of this study was to perform an integrated survival analysis of patients with bilateral thalamic glioma and to assess the influence of various prognostic factors on overall survival. METHODS A literature search of PubMed, Web of Science, and Google Scholar was performed for literature in English published from 1964 to May 2017. Detailed information including demographics, clinical characteristics, treatments, critical events, and time to events for survival analysis were extracted from the included articles. In addition, 2 cases diagnosed in our institution were included. RESULTS The study included 53 cases from 32 published articles and 2 cases from our institution that were selected for analysis. Univariate analysis showed the duration of symptoms (≥2 or