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Summary Background In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012–15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age–sex–residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20–1·72] and 12-month prevalence OR 1·41 [1·12–1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68–3·38] and 12-month OR 2·80 [95% CI 1·88–4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39–2·51] and 12-month OR 1·85 [95% CI 1·40–2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Objective We present prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with an abnormal first-trimester screening result, intrauterine growth restriction (IUGR) and a favorable outcome. Case report A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of an abnormal first-trimester screening result with maternal serum free β-hCG of 1.474 multiples of the median (MoM), pregnancy associated plasma protein-A (PAPP-A) of 0.122 MoM and placental growth factor (PlGF) of 0.101 MoM, and a Down syndrome risk of 1/45. Amniocentesis revealed a karyotype of 47,XY,+16 [9]/46,XY [16] and an abnormal array comparative genomic hybridization (aCGH) result of arr (16) × 3 [0.54] compatible with 54% mosaicism for trisomy 16 in uncultured amniocytes. At 24 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+16 [4]/46,XY [16] and an aCGH result of arr 16p13.3q24.3 (96,766–90,567,357) × 2.25 with a log2 ratio = 0.2 compatible with 20–30% mosaicism for trisomy 16 in uncultured amniocytes. Quantitative fluorescent polymerase chain reaction (QF-PCR) excluded uniparental disomy (UPD) 16. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 19.4% (12/62 cells) mosaic trisomy 16. Prenatal ultrasound revealed IUGR. At 36 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 1900 g. The cord blood had a karyotype of 46,XY. QF-PCR analysis confirmed biparentally inherited disomy 16 in the cord blood and maternal-origin of trisomy 16 in the placenta. When follow-up at age two months, FISH analysis on 101 buccal mucosal cells and 32 urinary cells revealed no signal of trisomy 16. Conclusion Mosaic trisomy 16 at amniocentesis can be associated with IUGR and an abnormal first-trimester screening result with low PAPP-A and low PlGF. Mosaic trisomy 16 without UPD 16 at amniocentesis can have a favorable outcome, and the abnormal triosmy 16 cell line may disappear after birth.

Objective To describe and discuss the progression of the non-coding RNA as biomarkers in early esophageal cancer. Background Esophageal cancer without obvious symptoms during early stages is one of the most common cancers, the current clinical treatments offer possibilities of a cure, but the survival rates and the prognoses remain poor, it is a serious threat to human life and health. Most patients are usually diagnosed during terminal stages due to low sensitivity of esophageal cancer’s early detection techniques. With the development of molecular biology, an increasing number of non-coding RNAs are found to be associated with the occurrence, development, and prognosis of esophageal cancer. Some of these have begun to be used in clinics and laboratories for diagnosis, treatment, and prognosis, with the goal of reducing mortality. Methods The information for this paper was collected from a variety of sources, including a search of the keynote’s references, a search for texts in college libraries, and discussions with experts in the field of esophageal cancer clinical treatment. Conclusions Non-coding RNA does play a regulatory role in the development of esophageal cancer, which can predict the occurrence or prognosis of tumors, and become a new class of tumor markers and therapeutic targets in clinical applications. In this review, we survey the recent developments in the incidence, diagnosis, and treatment of esophageal cancer, especially with new research progresses on non-coding RNA biomarkers in detail, and discuss its potential clinical applications.

Objective We present mosaic trisomy 15 at amniocentesis. Materials and methods A 41-year-old woman underwent amniocentesis at 16 weeks of gestation because of an abnormal non-invasive prenatal testing (NIPT) result suspicious of trisomy 15. Amniocentesis revealed a karyotype of 46,XY. Array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed 26% mosaicism for trisomy 15. She was referred for repeat amniocentesis. aCGH, interphase fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR) assays and/or conventional cytogenetic analysis were applied on various cells and tissues including uncultured amniocytes, cultured amniocytes, cord blood, placenta, parental bloods and/or buccal mucosal cells. Results Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46, XY in cultured amniocytes, and 30% mosaicism for trisomy 15 by aCGH and 32% mosaicism for trisomy 15 by FISH in uncultured amniocytes. Repeat amniocentesis at 29 weeks of gestation revealed a karyotype of 46, XY in cultured amniocytes, and 15% mosaicism for trisomy 15 by aCGH and 7.2% mosaicism for trisomy 15 by FISH in uncultured amniocytes. QF-PCR on cultured amniocytes excluded uniparental disomy (UPD) 15. A phenotypically normal baby was delivered subsequently with a karyotype of 46, XY in cord blood and 2% mosaicism for trisomy 15 by FISH in buccal mucosal cells. The aCGH analysis revealed trisomy 15 in placenta and no genomic imbalance in cord blood. QF-PCR assays determined a maternal origin of trisomy 15 in placenta. Conclusion Cytogenetic discrepancy may occur between uncultured and cultured amniocytes in mosaic trisomy 15 at amniocentesis. The cells of trisomy 15 cell line in prenatally detected mosaic trisomy 15 may decrease in number as the fetus grows. Whenever NIPT suspects trisomy 15, a confirmatory amniocentesis should include genetic analysis on both uncultured and cultured amniocytes to exclude mosaic trisomy 15 and maternal UPD 15, especially when the cultured amniocytes have a normal karyotype.

Objective We present perinatal molecular cytogenetic analysis of low-level mosaicism for trisomy 21 in a pregnancy with maternal uniparental disomy (UPD) of chromosome 21 in the fetus. Case report A 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+21[6]/46,XX[25]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (21) × 2–3, (X) × 2 with about 18% gene dosage increase in chromosome 21 consistent with mosaic trisomy 21. Cordocentesis was performed at 20 weeks of gestation, and the cord blood lymphocytes had a karyotype of 47,XX,+21[3]/46,XX[72]. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy. At 39 weeks of gestation, a 3,494-g phenotypically normal female baby was delivered without phenotypic features of Down syndrome. There was no dysplasia of middle phalanx of the fifth fingers of both hands. The cord blood had a karyotype of 47,XX,+21[2]/46,XX[48]. The placenta had a karyotype of 47,XX,+21[37]/46,XX[3]. The umbilical cord had a karyotype of 47,XX,+21[1]/46,XX[39]. aCGH analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis on the DNAs extracted from cord blood and parental bloods revealed maternal uniparental heterodisomy 21 in the baby. Interphase fluorescence in situ hybridization analysis on buccal mucosal cells revealed trisomy 21 signals in 15/101 (14.9%) buccal cells at birth and in 1/122 (0.82%) buccal cells at age 45 days. Conclusion Low-level mosaicism for trisomy 21 at amniocentesis associated with maternal UPD 21 in the fetus can have a favorable outcome.

Background Pediatric refractory epilepsy affects quality of life, clinical disability, and healthcare costs for patients and families. Objective To show the impact of surgical treatment for pediatric epilepsy on healthcare utilization compared to medically treated pediatric epilepsy over 5 yr. Methods The Pediatric Health Information System database was used to conduct a cohort study using 5 published algorithms. Refractory epilepsy patients treated with antiepileptic medications (AEDs) only or AEDs plus epilepsy surgery between 1/1/2008 and 12/31/2014 were included. Healthcare utilization following the index date at 2 and 5 yr including inpatient, emergency department (ED), and all epilepsy-related visits were evaluated. The propensity scores (PS) method was used to match surgically and medically treated patients. PS. SAS® 9.4 and Stata 14.0 were used for data management and statistical analysis. Results A total of 2106 (17.1%) and 10186 (82.9%) were surgically and medically treated. A total of 4050 matched cases, 2025 per each treated group, were included. Compared to medically treated patients, utilization was reduced in the surgical group: at 2 and 5 yr postindex date, there was a reduction of 36% to 37% of inpatient visits and 47% to 50% of ED visits. The total number (inpatient, ED, ambulatory visits) of epilepsy-associated visits were reduced by 39% to 43% in the surgical group compared to the medically treated group. In those who had surgery, the average reduction in AEDs was 16% at 2 and 5 yr after treatment. Conclusion Patients with refractory epilepsy treated with surgery had significant reductions in healthcare utilization compared with patients treated only with medications.

To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder (加味丁桂散, MDGP) in patients with chronic nonbacterial prostatitis (CNP). A randomized, double-blind, placebo-controlled clinical trial was conducted among 72 patients with CNP. Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio, and received either MDGP external umbilicus treatment (MDGP group, 36 cases) or placebo control groupl (36 cases) at acupoints Shenque (CV 8), twice a week for 4 weeks. In addtion, patients all received herbal medicine treatment twice a day for 4 weeks. The primary outcomes was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index (NIH-CPSI) with a questionnaire at weeks 2 and 4. The secondary outcomes including prostatic fluid examination (white blood cells and lecithin bodies), the clinical efficacy evaluation, and the adverse events were also assessed during the entire trial. The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2 (P0.001) and week 4 (P0.004), respectively. NIH-CPSI scores of symptom severity, total scores, the amount of leukocytes number in the prostatic fifluid in the MDGP group were significantly improved (P 0.05). The clinical effective rate was 73.53% (25/34) in the MDGP group, which was significally higher than the placebo control group with 48.39% (25/31, P

To describe 30-day outcomes following craniotomy for arteriovenous malformation in children and identify risk factors for readmission, reoperation, and perioperative complication using the National Surgical Quality Improvement Program (NSQIP) Pediatric database.Patients aged 0-18 years who underwent surgery for arteriovenous malformations (years 2015-2016) were identified from the NSQIP Pediatric database. Descriptive statistics, uni-variate, and multi-variate regression analysis were performed using preoperative and perioperative data. The outcome of interest was postoperative adverse event including reoperation within 30 days, readmission within 30 days, discharge to rehab, and the complications wound infection/dehiscence, pneumonia, unplanned reintubation, pulmonary embolism (PE), renal insufficiency, urinary tract infection (UTI), stroke, venous thromboembolism (VT), and sepsis.167 patients were identified who met study criteria. 58% were male, and the majority had an ASA classification of 3 or greater (68%). 96 (57%) patients were found to have a preoperative comorbidity, with the most common comorbidity being seizure disorder (54 patients, 32%). 76 patients (46%) had documented perioperative events or complications. The incidence of wound infection/dehiscence was 4%; and of pneumonia, PE, unplanned reintubation, renal insufficiency, UTI, stroke, VT, sepsis were1%. There were no deaths. The incidence of unplanned reoperation was 10% and unplanned readmission was 12%. Most (90%) were discharged to home. Operative time (p = .0001, OR = 9.53), emergent surgery status (p = .0001, OR = 8.19) and preoperative comorbidities (p = .007) were found to be significant predictors of poor outcome.In the NSQIP-P dataset, the incidence of perioperative complications and suboptimal outcomes among patients undergoing AVM resection were low.

Previous studies have shown hypothyroidism was independently associated with nonalcoholic fatty liver disease (NAFLD) in adults, but few studies examined their relationships in pediatric populations. This study aimed to investigate the prevalence of NAFLD in pediatric congenital hypothyroidism (CHT) patients and to identify the association between CHT and NAFLD. This study enrolled pediatric CHT patients receiving levothyroxine treatment at one medical center from 2013 to 2014. Euthyroid subjects (ET) and transient hypothyroidism (THT) patients weaned off medication successfully after age 3 were selected for further comparison. Laboratory data including thyroid functions, liver functions, and metabolic profiles were obtained. The major outcome was the occurrence of NAFLD, diagnosed based on the findings of abdominal ultrasonography. One‐hundred and twenty‐nine subjects (47 in CHT, 47 in THT, and 35 in ET groups) were enrolled. The analysis showed higher fasting serum glucose, insulin, thyroxine (T4), and mean thyroid‐stimulating hormone (TSH) levels in the CHT group. NAFLD prevalence was higher in the CHT (23.4%) group than in the THT (8.5%) and the ET (5.7%) groups, demonstrating an increasing trend across three strata (X2linear‐by‐linear = 5.9, P

Background: Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder characterized by severe intrauterine growth retardation, poor postnatal growth, characteristic facial features, and body asymmetry. Hypomethylation of the imprinted genes of the chromosome 11p15.5 imprinting gene cluster and maternal uniparental disomy of chromosome 7 (mUPD7) are the major epigenetic disturbances. The aim of this study was to characterize the epigenotype, genotype, and phenotype of these patients in Taiwan. Methods: Two hundred and six subjects with clinically suspected SRS were referred for diagnostic testing, which was performed by profiling the methylation of H19-associated imprinting center (IC) 1 and the imprinted PEG1/MEST region using methylation-specific multiplex ligation-dependent probe amplification and high-resolution melting analysis with a methylation-specific polymerase chain reaction assay. We also applied a whole genome strategy to detect copy number changes and loss of heterozygosity. Clinical manifestations were recorded and analyzed according to the SRS scoring system proposed by Bartholdi et al. Results: Among the 206 referred subjects, 100 were classified as having a clinical diagnosis of SRS (score ≥ 8, maximum = 15) and 106 had an SRS score ≤ 7. Molecular lesions were detected in 45% (45/100) of the subjects with a clinical diagnosis of SRS, compared to 5% (5/106) of those with an SRS score ≤ 7. Thirty-seven subjects had IC1 hypomethylation, ten subjects had mUPD7, and three subjects had microdeletions. Several clinical features were found to be statistically different (p &lt, 0.05) between the “IC1 hypomethylation” and “mUPD7” groups, including relative macrocephaly at birth (89% vs. 50%), triangular shaped face (89% vs. 50%), clinodactyly of the fifth finger (68% vs. 20%), and SRS score (11.4 ± 2.2 vs. 8.3 ± 2.5). Conclusions: The SRS score was positively correlated with the molecular diagnosis rate (p &lt, 0.001). The SRS subjects with mUPD7 seemed to have fewer typical features and lower SRS scores than those with IC1 hypomethylation. Careful clinical observation and timely molecular confirmation are important to allow for an early diagnosis and multidisciplinary management of these patients.

Background and Objectives: Insulin treatment may be initially required to stabilize patients presenting with metabolic crisis at type 1 and 2 diabetes mellitus (DM) onset. Some patients with type 2 DM may need persistent insulin treatment. This study aimed to examine the predictive performance of non-stimulated C-peptide level at the time of diagnosis for future insulin use in pediatric diabetic patients. Materials and Methods: We reviewed the medical charts of diabetic patients aged 18 years or younger in a medical center in southern Taiwan from January 2000 to December 2019. Clinical and individual data were collected at the time of DM diagnosis. Outcomes were persistent insulin use at the time of diagnosis, as well as at one and two years after diagnosis. Results: The final analysis included a total of 250 patients. The best cut-off point of non-stimulated C-peptide was 0.95 ng/mL, and the predictive indices for the insulin use were 0.84 for sensitivity and 0.94 for specificity at two years after DM diagnosis. Incorporating age at onset and presence of GAD antibodies can further increase the predictive power of non-stimulated C-peptide. Conclusions: The value of non-stimulated C-peptide at diabetic onset was feasible and effective for predicting future insulin treatment up to the time point of two years after diagnosis.

Background Development of a deep learning method to identify Barrett's esophagus (BE) scopes in endoscopic images. Methods 443 endoscopic images from 187 patients of BE were included in this study. The gastroesophageal junction (GEJ) and squamous-columnar junction (SCJ) of BE were manually annotated in endoscopic images by experts. Fully convolutional neural networks (FCN) were developed to automatically identify the BE scopes in endoscopic images. The networks were trained and evaluated in two separate image sets. The performance of segmentation was evaluated by intersection over union (IOU). Results The deep learning method was proved to be satisfying in the automated identification of BE in endoscopic images. The values of the IOU were 0.56 (GEJ) and 0.82 (SCJ), respectively. Conclusions Deep learning algorithm is promising with accuracies of concordance with manual human assessment in segmentation of the BE scope in endoscopic images. This automated recognition method helps clinicians to locate and recognize the scopes of BE in endoscopic examinations.

Objective We present prenatal diagnosis of maternal uniparental disomy (UPD) 5 by amniocentesis associated with confined placental mosaicism (CPM) for trisomy 5 and fetal trisomy 21 in a pregnancy. Case report A 45-year-old woman underwent chorionic villus sampling (CVS) at 11 weeks of gestation because of maternal advanced age and an increased nuchal translucency of 4.0 mm in the first-trimester screening. CVS revealed a karyotype of 47,XY,+21[98]/48,XY,+5,+21[25]. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from chorionic villi revealed arr (5) × 3, arr (21) × 3 compatible with double trisomy 5 and trisomy 21. The woman underwent amniocenteses at 20 weeks and 22 weeks of gestation. Amniocenteses revealed a karyotype of 47,XY,+21. The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) on the DNA extracted from uncultured amniocytes showed trisomy 21 of maternal origin and maternal UPD 5. aCGH and interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes confirmed trisomy 21. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a 2,198-g male baby was delivered at 38 weeks of gestation with characteristic phenotype of Down syndrome of hypertelorism, epicanthic folds and hypoplastic middle phalanx of the fifth fingers. Cytogenetic analysis of cord blood, umbilical cord and placenta revealed a karyotype of 47,XY,+21. QF-PCR analysis of the DNA extracted from placenta revealed double trisomy 5 and trisomy 21 with maternal gene dosage increase in chromosome 5 and chromosome 21. Conclusion Prenatal diagnosis of CPM for trisomy 5 at CVS can be associated with UPD 5 in the fetus, and UPD 5 causes no specific phenotype.

Background The lack of rapid and efficient diagnostic methods has been one of the most frustrating challenges in controlling the pulmonary tuberculosis (TB) epidemic. This study was aimed to identify novel non-invasive biomarkers for pulmonary TB. Methods The subjects in this study were divided into four groups: the pulmonary TB group, the community-acquired pneumonia (CAP) group, the lung cancer (LC) group, and the normal control (NC) group. Plasma small molecule metabolites were investigated in each group by using ultra-high performance liquid chromatography coupled with Q Exactive mass spectrometry. Multivariate statistical methods and bioinformatics were used to analyze the data. Results We identified three differential plasma metabolites such as, Xanthine, 4-Pyridoxate and d -glutamic acid in the pulmonary TB group, compared to the other groups (CAP, LC and NC). The pathway enrichment analysis indicated that the energy source in pulmonary TB was multi-center, which might be involved in maintaining the reproductive ability and virulence of Mycobacterium tuberculosis. Conclusion The results suggested that Xanthine, 4-Pyridoxate, and d -glutamic acid may serve as potential biomarkers for pulmonary TB. The present study provides experimental basis for developing potential biomarkers of pulmonary TB.

Background Hypothalamic hamartomas (HH) are a challenging pathology that cause gelastic seizures. Magnetic Resonance Imaging-guided Laser Interstitial Thermal Therapy (MRgLITT) offers a safe and effective treatment for HHs via a minimally invasive technique. Objective To determine how clinical outcome correlates to residual tumor volume and surgical strategy by analyzing radiographic data and reconstructing volumetric imaging. Methods Clinical and radiographic information of 58 pediatric patients who underwent MRgLITT for HH with at least 6 mo of follow-up were retrospectively reviewed. MR imaging was volumetrically reconstructed to analyze the impact of hamartoma and ablation volumes on outcome. Primary outcome measure was freedom from gelastic seizures. Results Eighty-one percent of patients were completely free of gelastic seizures at last follow-up; of 22 patients with secondary nongelastic epilepsy, 15 were free of additional seizures. Postoperative complication rate was low. There was no significant difference in gelastic seizure outcome related to pre- or postoperative hamartoma size. Residual hamartoma percentage in those free of gelastic seizures was 43% compared to 71% in those with continued seizures (P = .021). Larger hamartomas required multiple ablations to achieve seizure freedom. Conclusion This large series of patients confirms the safety and efficacy of MRgLITT for pediatric HH and describes morphological considerations that predict success. Our data suggest that complete ablation of the lesion is not necessary, and that the focus should be on appropriate disconnection of the epileptogenic network. We have found that a staged approach to hamartoma ablation allows adequate disconnection of the hamartoma while mitigating risk to surrounding structures.

Introduction: Brain glioma is the most common type of primary malignancy in the central nervous system (CNS), with high recurrence and mortality rate, especially glioblastoma (GBM). Recent evidence suggests a role for many long noncoding RNAs (lncRNAs) in the pathogenesis, proliferation, apoptosis, metastasis, and chemotherapeutic resistance of cancer cells. Although the functions of some lncRNAs in the occurrence and development of gliomas have been confirmed, detailed mechanisms of action are lacking. Furthermore, the biological roles of many other lncRNAs in glioma have not been reported at all. Methods: In this study, we identified a novel lncRNA, UBE2R2-AS1, which was dramatically downregulated in glioma compared with normal tissue, by performing microarray detection of six pairs of glioma samples and adjacent normal tissues. In vitro experiments demonstrated that UBE2R2-AS1 regulated glioma cell proliferation, apoptosis, and migration. Results: UBE2R2-AS1 acted as a competing endogenous RNA (ceRNA) to target Toll-like receptor 4 (TLR4) mRNA by binding to miR-877-3p. Furthermore, lncRNA UBE2R2-AS1 suppressed glioblastoma cell growth, migration, and invasion, as well as promoting cell apoptosis by targeting miR-877-3p/TLR4 directly. Conclusion: This information regarding UBE2R2-AS1 and its glioma-related molecular mechanisms will aid the future identification of new lncRNA-directed diagnostics and drug-targeting therapies.

Chiari malformation type 1 (CM-1) is a common congenital or acquired malformation of the posterior fossa. We aimed to characterize preoperative risk factors, perioperative complications, and postoperative outcomes related to CM-1 surgery in pediatric populations across a nationwide network of pediatric hospitals in the United States (US). The Children’s Hospital Association’s Pediatric Health Information System (PHIS) database was used to examine patients

Primary congenital hypothyroidism is a disease associated with low serum thyroxine and elevated thyroid-stimulating hormone (TSH) levels. The processes of screening and treating congenital hypothyroidism, in order to prevent neurodevelopmental impairment (NDI) in newborns, have been well investigated. Unlike term infants, very preterm infants (VPIs) may experience low thyroxine with normal TSH levels (&lt, 10.0 μIU/mL) during long-stay hospitalization. In the current literature, thyroxine treatment has been evaluated only for TSH-elevated VPIs. However, the long-term impact of low thyroxine levels in certain VPIs with normal TSH levels deserves more research. Since July 2007, VPIs of this study unit received screenings at 1 month postnatal age (PNA) for serum TSH levels and total thyroxine (TT4), in addition to two national TSH screenings scheduled at 3–5 days PNA and at term equivalent age. This study aimed to establish the correlation between postnatal 1-month-old TT4 concentration and long-term NDI at 24 months corrected age among VPIs with serial normal TSH levels. VPIs born in August 2007–July 2016 were enrolled. Perinatal demography, hospitalization morbidities, and thyroid function profiles were analyzed, and we excluded those with congenital anomalies, brain injuries, elevated TSH levels, or a history of thyroxine treatments. In total, 334 VPIs were analyzed and 302 (90.4%) VPIs were followed-up. The postnatal TT4 concentration was not associated with NDI after multivariate adjustment (odd ratios 1.131, 95% confidence interval 0.969–1.32). To attribute the NDI of TSH-normal VPIs to a single postnatal TT4 concentration measurement may require more research.

Our previous study showed that the lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis through the miR-877-3p/TLR4 pathway. In this study, it was further found that the expression of UBE2R2-AS1 in glioma tissues was decreased significantly, and gradually decreased with increasing clinical stage. Chi-square analysis showed that the expression of UBE2R2-AS1 was significantly correlated with the WHO stage of tumor and epilepsy. Using Kaplan-Meier univariate survival analysis, it was found that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma, while multiple Cox regression analysis showed that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma as a protective factor for glioma prognosis. The analysis of data from TCGA also showed that patients with high UBE2R2-AS1 levels or low miR-877-3p expression were more likely to have good survival outcomes. Further construction of a glioma xenograft model in nude mice showed that UBE2R2-AS1 overexpression inhibited the growth of tumors, and the inhibition of miR-877-3p expression had a similar effect. Simultaneous UBE2R2-AS1 overexpression and miR-877-3p inhibition further decreased the growth rate of tumors in nude mice. Taken together, the results of our study suggest that UBE2R2-AS1 is an important tumor suppressor gene in glioma, which may be a good marker and treatment target for the clinical detection of glioma.

Glioma is the most common primary malignant tumor of the central nervous system and has a poor prognosis. Therefore, exploring the key molecular targets is a new opportunity for basic research and clinical treatment of glioma. Previous studies found that circRNA-hsa_circ_0073237 was upregulated in gliomas. Our further analyses of the biological function and molecular mechanism of hsa_circ_0073237 showed that hsa_circ_0073237 was also upregulated in glioma cell lines and could combine with miR-345 to inhibit its expression. miR-345 was downregulated in glioma tissues and cells, and targeted to regulate the expression of hepatoma-derived growth factor (HDGF), while HDGF expression was enhanced in glioma. Hsa_circ_0073237 promoted the expression of HDGF in glioma cells by adsorbing miR-345. Hsa_circ_0073237 siRNA, miR-345, and HDGF siRNA effectively inhibited cell viability and invasion and promoted cell apoptosis. When expression of hsa_circ_0073237 and miR-345 was inhibited simultaneously, cell viability, apoptosis, and invasion did not change significantly; however, after transfection with HDGF overexpression vector, the effects of hsa_circ_0073237 siRNA and miR-345 on glioma cell viability, apoptosis, and invasion were obviously reversed. Further construction of glioma xenograft models in nude mice confirmed that the introduction of miR-345 in vivo effectively inhibited tumor growth, significantly reduced tumor diameter and weight, and obviously decreased the expression of HDGF. Therefore, hsa_circ_0073237 can regulate the biological functions of glioma cells through miR-345/HDGF, thereby affecting the progression of tumors, indicating that the hsa_circ_0073237/miR-345/HDGF pathway may be a key target for the treatment of glioma.

IntroductionThe aim of this study was to evaluate diagnostic performance of wireless fractional flow reserve (FFR) used in patients with coronary artery disease (CAD).Material and methodsPubMed, Cochrane Library, Embase and Clinical trial.gov databases were searched by computer search and manual retrieval. The search terms included fractional flow reserve, quantitative coronary angiography, computational fluid dynamics and coronary artery disease. The meta-analysis was conducted with Stata12.0. Clinical outcomes included accuracy, sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (–LR), diagnostic odds ratio (DOR) and area under the receiver operating curve.ResultsNine studies comprising 2052 vessels were included in the present meta-analysis. The sensitivity, specificity, +LR, –LR, DOC and accuracy were 87% (95% CI: 83–94%), 88% (95% CI: 82–92%), 7.28 (95% CI: 4.78–11.08), 0.14 (95% CI: 0.10–0.21), 50.69 (95% CI: 25.22–101.88) and 0.94 (95% CI: 0.91–0.96) respectively. No significant publication bias was detected.ConclusionsThis meta-analysis suggests that the clinical performance such as accuracy, sensitivity and specificity of wireless FFR is good to detect stenotic lesions with pressure-wire measured FFR as a reference.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability (YLDs). However, nationally representative epidemiological data for depressive disorders, in particular depressed adults’ mental health services use, are still unavailable in China. The present study is a part of the Chinese National Mental Health Survey (CMHS), 2012–15, which reported the prevalence, treatment, and associated disability of depressive disorders in the Chinese general population. Methods: The CMHS recruited a representative sample of 28140 Chinese residents (≥ 18 years) by using multistage proportional-to-population-size sampling method. Trained investigators interviewed participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder (MDD), dysthymic disorder (DD), and depressive disorder not otherwise specified (DD-NOS). Participants with 12-month depressive disorders were asked whether they ever received any 12-month treatment for their emotional problems and the specific types of treatment providers. The Quick Inventory of Depressive Symptomatology and Sheehan Disability Scale (SDS) were used to evaluate the severity of and role impairments associated with 12-month depressive symptoms. Findings: The weighted lifetime and 12-month prevalence rates of any depressive disorder were 6.8% (95%CI: 5.8-7.8%) and 3.6% (95%CI: 3.0-4.2%), respectively; the corresponding figures were 3.4% (95%CI: 2.0-3.9%) and 2.1% (95%CI: 1.8-2.4%) for MDD, 1.4% (95%CI: 1.1-1.7%) and 1.0% (95%CI: 0.8-1.3%) for DD, and 3.2% (95%CI: 2.6-3.9%) and 1.4% (95%CI: 1.1-1.7%) for DD-NOS. Overall, 77.2% of persons with 12-month depressive disorders had role impairment of any SDS domain: 82.2% for MDD, 81.5% for DD, and 64.6% for DD-NOS. Depressed participants reported an average of 41.0 days out of role in the past year due to depression; the corresponding figures were 49.7 days for MDD, 54.9 days for DD, and 12.2 days for DD-NOS. In total, 88.9% of individuals with 12-month depressive disorders had clinically significant depressive symptoms: 93.7% for MDD, 91.7% for DD, and 77.5% for DD-NOS. MDD and DD had similar proportions of “severe” or “very severe” depressive symptoms (43.0% and 42.1%), which were higher than DD-NOS (13.9%). 9.5% of participants with 12-month depressive disorders were treated in any treatment sector: 3.6% in the specialty mental health (SMH), 1.5% in the general medical (GM), 0.3% in the human services (HS), and 3.3% in the complementary-alternative medical (CAM) sector. Respondents with MDD and DYS had the highest proportion of seeking treatment in SMH sector (4.7% and 3.0%) while those with DD-NOS had the highest proportion of seeking treatment in CAM sector (most treatments were Traditional Chinese Medicine) (3.3%). Only 0.5% of participants with depressive disorders were treated adequately. Rates of treatment adequacy of MDD and DYS in SMH sector were 9.2% and 2.4%, respectively. Both rates in GM sector were 0%. Interpretation: Compared to western countries, our data show a relatively low prevalence of depressive disorders in China. Nevertheless, their associated role impairments, symptom severities, and disabilities are severe. Importantly, the treatment rates are rather low, let alone adequate treatment. Nationwide programs aiming at removing barriers in availability, accessibility, and acceptability to mental healthcare are needed in China. Funding: The study was funded by the Special Research Project for Non-profit Public Service of the Chinese Ministry of Health (grant number 201202022), the National Twelfth Five-Year Plan for Science and Technology Support of the Chinese Ministry of Science and Technology (grant numbers 2012BAI01B01 & 2015BAI13B00) and the National Key R&D Program of China (grant numbers 2017YFC0907800, 2017YFC0907801). Declaration of Interests: The authors have no conflicts of interest to declare Ethical Approval: The study protocol of CMHS was approved by the Ethics Committee of the Sixth Hospital of Peking University (No.: IMH-IRB-2013-13-1).

Sepsis is a clinical syndrome that resulting from a dysregulated inflammatory response to infection that leads to organ dysfunction. The dysregulated inflammatory response transitions from a hyper-inflammatory phase to a hypo-inflammatory or immunosuppressive phase. Currently, no phase-specific molecular-based therapies are available for monitoring the complex immune response and treating sepsis due to individual variations in the timing and overlap of the dysregulated immune response in most patients. Glucocorticoid-induced leucine zipper (GILZ), is broadly present in multiple tissues and circumvent glucocorticoid resistance (GCR) or unwanted side effects. Recently, the characteristics of GILZ downregulation during acute hyperinflammation and GILZ upregulation during the immunosuppressive phase in various inflammatory diseases have been well documented, and the protective effects of GILZ have gained attention in the field of sepsis. However, whether GILZ could be a promising candidate biomarker for monitoring and treating septic patients remains unknown. Here, we discuss the effect of GILZ in sepsis and sepsis-induced immunosuppression.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial membrane hyperplasia, infiltration of inflammatory cells and bone tissue destruction. Although there have been many measures taken for RA therapy in recent years, they are not sufficiently safe or effective. Thus, it is very important to develop new drugs and slow down damage to other healthy organs in the case of RA. Lately, immunoglobulin Fc receptors (FcRs), such as the IgG Fc receptor (FcγR), IgA Fc receptor (FcαR), and IgD Fc receptor (FcδR), have been found to be involved in inducing or suppressing arthritis. FcRs interacting with immune complexes (ICs) are a key factor in the etiopathogenesis of RA. Therefore, an increasing number of methods for the targeted treatment of RA with FcRs are emerging, such as recombinant soluble FcγRs, recombinant multimeric Fc fragments and monoclonal antibodies, and have been demonstrated to significantly improve RA symptoms. Simultaneously, certain kinases involved in the downstream signaling of FcRs can also be a target for the treatment of RA, such as Syk and Btk inhibitors. An overview of these FcRs is provided in this review, including a description of FcR-related functions, signaling pathways, and potential FcR-targeting molecules for RA therapy. To date, the initial results of those developed FcR-targeting molecules have been promising. With this, FcRs might offer a better alternative to RA medication. Additionally, further pharmacological characterization and a better understanding of the unique mechanisms of FcR-targeting molecules are necessary.

This study investigated the role of vision in maintaining stroke synchronization in crew-boat sprint kayaking. Sixteen sprint kayakers from a national team were paired into eight two-seater (K2) crews. Each crew paddled at high intensity with the back paddler's eyes open or closed in a randomized order. Using video analysis, stroke synchronization was quantified by the timing offsets between the front and back paddlers at four key positions of the stroke. All crews could paddle continuously without capsize or stopping under both visual conditions. In the absence of vision, neither 200-m performance time (p = 0.23, d = 0.47, small effect size) nor stroke rate (p = 0.41, d = 0.31, small effect size) was severely affected. There were no significant effects of vision on stroke synchronization offsets between the front and back paddlers across all key positions (all p > 0.05). Highly skilled paddlers likely relied on the kinesthetic perception to maintain the boat synchronization when visual information was not available.

BACKGROUND: To investigate the prognostic value of a novel immune-inflammatory index, the interleukin-6-to-lymphocyte ratio (IL-6/LY), with the clinical outcomes of severe coronavirus disease 2019 (COVID-19) cases. METHODS: A cohort study of COVID-19 patients in Tongji Hospital, from January 2020 to February 2020, was evaluated. Kaplan-Meier method and the log-rank test was performed to analyze survival data. Univariate and multivariate analyses were performed with COX proportional hazard regression model. The primary and secondary outcomes were in-hospital mortality and multiple organ dysfunction syndrome (MODS), respectively. RESULTS: Total 320 adult patients were enrolled in our analyses. Patients were divided into low IL-6/LY group and high IL-6/LY group based on the cutoff value with 2.50. The Kaplan-Meier survival curves showed that high-value group (IL-6/LY ≥ 2.50) had a greater risk of poor prognosis (P

Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the immune system attacking islet cells. T1D, with a long prediabetes period, and the incidence of T1D increases with age during childhood and peaks at 10-14 years. And once it gets overt, it requires lifelong insulin replace treatment. Therefore, the diagnosis of early-stage T1D and effective treatments are important for the management of T1D patients. The imaging methods, such as magnetic resonance imaging (MRI) and so on, were applied in diagnosis of the early stage T1D and its development tracking. The addition of nanomaterials, especially in MRI, can improve the quality of T1D imaging for the diagnosis of T1D at early stage and cause less harm to human body. Meantime, among various treatment options, islet transplantation and immunotherapy are promising, effective, and less independent on insulin. The addition of nanotechnology can effectively reduce the attack of the immune system on drugs and cells, making the therapeutic drug more targeted in the body and prolonging the action time between drugs and cells, thus its addition makes these therapy safer and more efficient. In this review, we attempt to summarize the recent advances in the development of nanotechnology advances of T1D including using nanomaterials for the diagnosis and immunological imaging of T1D, protecting the transplanted islet cells from immune system attack, and delivering relevant molecules to targeted immunocytes. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.

Background The stiffness of the first metatarsophalangeal joint (MTPJ) is of interest in cases such as hallux rigidus and apropulsive gait. Subjective rating of joint mobility as ‘hypermobile, normal, or stiff’ is an unreliable method. Previous instruments for the assessment of first MTPJ stiffness can be too hard and uncomfortable for test subjects. Recently, a new device using a load cell and optical fiber with fiber Bragg grating (FBG) sensors was developed to provide a comfortable means of clinical foot assessment. This study aimed to evaluate the test-retest reliability of this FBG-load cell device in measuring the first MTPJ quasi-stiffness. Methods The left foot of 13 female subjects were measured twice for their first MTPJ quasi-stiffness, approximately seven days apart. The FBG-load cell device measured the MTPJ range of motion from a resting position to maximum dorsiflexion and then returning to the resting start-position. The force applied by a clinician to displace the toe was simultaneously recorded using the load cell. The quasi-stiffness over the “working range” in loading and unloading directions were determined from the slope of the torque-angular displacement graph. The test-retest reliability of the MTPJ quasi-stiffness was evaluated using intra-class correlation coefficient [ICC (2,1)]. Results The reliability was almost perfect for MTPJ quasi-stiffness over the loading phase (ICC = 0.814), moderate for MTPJ quasi-stiffness over the unloading phase (ICC = 0.477) and moderate for MTPJ maximum range (ICC = 0.486). Conclusion The foot assessment device comprising FBG and load cell was able to reliably measure the first MTPJ quasi-stiffness in a clinical setting. The measurement reliability was higher during the loading phase than the unloading phase.

OBJECTIVENumerous surgical procedures facilitate revascularization of the ischemic brain in patients with moyamoya disease. Dural inversion is a technique in which flaps of dura mater centered around the middle meningeal artery are inverted, encouraging the formation of a rich collateral blood supply. This procedure has been used in combination with encephaloduroarteriosynangiosis for more than 20 years at the authors’ institution for the treatment of pediatric moyamoya disease. The objective of this study was to describe the clinical and radiographic outcomes for a cohort of consecutive pediatric moyamoya patients undergoing dural inversion.METHODSClinical and radiographic data on patients who had undergone dural inversion in the period from 1997 to 2016 were reviewed. Univariate and multivariate logistic regression and Kaplan-Meier analyses were performed to assess the risk of postoperative stroke, functional outcome, and the angiographic degree of revascularization.RESULTSDural inversion was performed on 169 hemispheres in 102 patients. Median follow-up was 4.3 years. Six patients (3.6% of hemispheres) suffered postoperative ischemic or hemorrhagic stroke. Overall mortality was 1.0%. Good postoperative neurological status (modified Rankin Scale [mRS] score ≤ 2) was observed in 90 patients (88%); preoperative and postoperative mRS scores showed significant improvement (p < 0.001). Eighty-six percent of hemispheres had Matsushima grade A or B revascularization. Younger age was associated with postoperative stroke and poor functional outcome. Patients with secondary moyamoya syndrome had a significantly worse radiographic outcome. The cumulative 5-year Kaplan-Meier risk for stroke was 6.4%.CONCLUSIONSDural inversion is a useful technique of cerebral revascularization in pediatric moyamoya disease. A 20-year experience demonstrates the safety and efficacy of this technique with a relatively low rate of postoperative stroke, good functional outcomes, and favorable angiographic results.

Exosomes are important carriers of biological information that facilitate intercellular communication and participate in the pathophysiology of different cardiovascular diseases. Myocardial infarction is among the leading causes of death worldwide. Upon myocardial infarction, massive cardiomyocyte death triggers a strong inflammatory response which is a vital process of cardiac injury, repair, and remodeling. Increasing evidence has unveiled that exosomes are involved in the inflammatory response and immune regulation after myocardial infarction. In this review, we will summarize the biological function of exosomes in the pathophysiology of myocardial infarction, especially focusing on their roles in the modulation of inflammation and immune response after myocardial infarction which further influences myocardial repair and remodeling. We will also discuss the immunomodulation by exosomes derived from stem and progenitor cells in the treatment of myocardial infarction. A deep understanding of immunomodulation by exosomes may represent a promising therapeutic option for the treatment of myocardial infarction.

Objective We present two cases of late-onset bilateral fetal pleural effusions associated with fetal Down syndrome. Case reports Case 1. A 33-year-old Vietnamese woman had undergone regular sonographic examinations since 23 weeks of gestation and no abnormality had been noted. However, bilateral moderate pleural effusions were found at 33 weeks of gestation, and massive pleural effusion, ascites and polyhydramnios developed at 34 weeks of gestation. Aspiration of the pleural effusion was subsequently performed. Clinical laboratory surveys of the aspiration fluid excluded toxoplasmosis and cytomegalovirus infection. Cytogenetic analysis of cultured lymphocytes derived from pleural effusion revealed a karyotype of 47,XX,+21. The parents elected to continue the pregnancy. Intrauterine fetal demise occurred at 37 weeks of gestation, and a macerated female baby was delivered. Postnatal cytogenetic analysis of the umbilical cord confirmed the prenatal diagnosis. Case 2. A 41-year-old Pakistani woman had undergone regular sonographic examinations and no abnormality had been noted. However, isolated bilateral mild pleural effusions were noted at 27 weeks of gestation. Amniocentesis revealed a karyotype of 47,XY,+21 and simultaneous array comparative genomic hybridization analysis of uncultured amniocytes confirmed the diagnosis of Down syndrome. The pregnancy was subsequently terminated. Conclusion Fetuses with Down syndrome may present late-onset bilateral pleural effusions. Prenatal diagnosis of late-onset bilateral pleural effusions should raise the possibility of fetal Down syndrome and cytogenetic investigation is warranted.

Glioblastoma (GBM) is a rare malignancy in children. The United States Surveillance, Epidemiology, and End Results (SEER) database allows large-scale analyses of clinical characteristics and prognostic features. We used it to study patients aged20 years with histologically confirmed GBM (2000-2010) and examined the relationship between patient demographics, tumor characteristics, patterns of treatment, and outcomes. The primary outcome was disease-specific survival. 302 subjects were identified, with median age 11 years. Median follow-up was 32 months (95% CI 27-39). 34.4% had gross total resection (GTR). 61% underwent radiation after surgery (17% of subjects3 years, 67% of those aged 4-19 years). Median survival and 2-year survival rates were 20 months and 46.9%, respectively. In multivariate analyses, age, tumor location, extent of resection, and year of diagnosis were significantly associated with the primary outcome. Compared to those aged 0-4 years, subjects aged 5-9 years and 10-14 years had higher risk of mortality. Infratentorial tumor location (HR 2.0, 95% CI 1.2-3.3, p = 0.007) and subtotal resection (HR 2.04, 95% CI 1.4-3.0, p 0.001) were associated with increased mortality. Later year of diagnosis was significantly associated with decreased risk of death (HR 0.93, 95% CI 0.9-0.99, p = 0.031). There was no association between sex, race, region, or tumor size and the primary outcome. Repeat analyses examining all-cause mortality identified the same risk factors as for CNS cancer-specific mortality. Younger age, supratentorial location, GTR, and later year of diagnosis were associated with improved survival.

The aim of this study was to use the multicenter American College of Surgeons National Surgical Quality Improvement Program–Pediatric (NSQIP-P) to evaluate and identify risk factors for 30-day adverse events in children undergoing epilepsy surgery. Using the 2015 NSQIP-P database, we identified children (age 0–18 years) undergoing pediatric epilepsy surgery and analyzed NSQIP-defined complications, unplanned reoperations, and unplanned readmissions. Multivariable logistic regression analysis was performed using perioperative data to identify risk factors for adverse events within 30 days of the index procedure. Two hundred eight pediatric patients undergoing epilepsy surgery were identified for the year 2015 in the NSQIP-P database. The majority of patients were male (51.8%) and white (72.9%). The median age was 10 years. Neurological and neuromuscular comorbidities were seen in 62.5% of patients. Surgical blood loss and transfusion was the most common overall NSQIP-defined event (15.7%) and was reported in 40% with hemispherectomy. Nineteen patients (6.8%) had an unplanned reoperation and 20 patients (7.1%) had an unplanned readmission. Multivariable logistic regression analysis showed that African American patients (OR 3.26, 95% CI 1.29–8.21, p = 0.01) and hemispherectomy (OR 3.05, 95% CI 1.4–6.65, p = 0.01) were independently associated with NSQIP-defined complications. Patients undergoing hemispherectomy (OR 4.11, 95% CI 1.48–11.42, p = 0.01) were also at significantly higher risk of unplanned readmission after pediatric epilepsy surgery. Data from the 2015 NSQIP-P database showed that hemispherectomy was significantly associated with higher perioperative events in children undergoing epilepsy surgery. Quality improvement initiatives for hemispherectomy should target surgical blood loss and wound-related complications. Racial disparities in access to cranial pediatric epilepsy surgery and perioperative complications were also highlighted in the present study.

Objective We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 16. Case report A 28-year-old woman underwent amniocentesis at 17 weeks of gestation because of abnormal maternal serum screening for Down syndrome. Amniocentesis revealed a karyotype of 47,XY,+mar[5]/46,XY[9]. Parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis of cultured amniocytes revealed a de novo 16% gene dosage increase of 16q11.2-q22.1. Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 47,XY,+mar[10]/46,XY[31]. aCGH analysis of uncultured amniocytes revealed a result of arr 16q11.2q22.1 (46,492,626–68,867,969) × 2.20 with a log2 ratio of 0.15 encompassing RPGRIP1L , FTO , SLC6A2 , BBS2 and CDH1 . Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected partial trisomy 16q in 36/137 (26.3%) of uncultured amniocytes. Polymorphic DNA marker analysis on amniocytes and parental bloods excluded uniparental disomy 16. Premature labor occurred at 25 weeks of gestation, and a 585-g male baby without craniofacial dysmorphism was delivered and survived. At age 1½ years, pediatric follow-ups revealed normal psychomotor development, normal body weight, short stature, congenital hypothyroidism, hearing impairment and hypospadias in the neonate, and the peripheral blood had a karyotype of 46,XY in 40 cultured lymphocytes. Conclusion aCGH, interphase FISH and polymorphic DNA marker analyses of uncultured amniocytes are useful for confirmation of prenatally detected mosaic sSMCs at amniocentesis.

Objective We present the association of paternal uniparental disomy (UPD) 9 with mosaicism for a small supernumerary marker chromosome 9 [sSMC(9)] and a supernumerary ring chromosome 9 [r(9)]. Materials and methods A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+mar [25]/48,XY,+mar,+r(9) [4]/47,XY,+r(9) [1]/46,XY [6]. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) of cultured amniocytes revealed a result of de novo 9p13.1q21.11 (38,792,472–71,026,063) × 2.64. The marker chromosome was determined to be an sSMC(9) by spectral karyotyping and aCGH. A phenotypically normal baby was delivered at 38 weeks of gestation. During pediatric follow-ups at age two years, the neonate manifested normal psychomotor and growth development. Cytogenetic analysis, metaphase fluorescence in situ hybridization (FISH), single nucleotide polymorphism (SNP) aCGH and polymorphic DNA marker analysis were performed on the peripheral blood of the neonate. Results The neonate's blood had the following results. Metaphase FISH confirmed coexistence of the sSMC(9) and the supernumerary r(9). The karyotype was 47,XY,+sSMC(9) [14]/48,XY, +sSMC(9),+r(9) [10]/47,XY,+r(9) [6]/46,XY [10]. SNP aCGH revealed arr 9p22.3q21.11 (14,234,165–71,035,608) × 2–3, arr 9p24.3p22.3 (216,123–14,629,321)hmz, arr 9p21.3p13.2 (24,769,722–36,732,597)hmz and arr 9q21.11q34.3 (71,013,799–141,011,581)hmz. Polymorphic DNA marker analysis showed paternal isodisomy 9. Conclusion Individuals with mosaicism for sSMC(9) and supernumerary r(9) may be associated with paternal UPD 9.

Objective We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 11. Case report A 37-year-old, gravida 3, para 2, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+mar[18]/46,XX[4]. The parental karyotypes were normal. Level II ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) on the DNA extracted from cultured amniocytes revealed no genomic imbalance. The sSMC was characterized by spectral karyotyping (SKY) using 24-color SKY probes and fluorescence in situ hybridization (FISH) using a whole chromosome paint (wcp) probe and a CEP11 (D11Z1) probe. The result was 47,XX,+mar.ish(11)(SKY+, wcp11+, D11Z1+)[16]/46,XX[4], indicating that the sSMC was derived from chromosome 11. A healthy female baby was delivered at 37 weeks of gestation with no phenotypic abnormalities. The cord blood had a karyotype of 47,XX,+mar[32]/46,XX[8]. Polymorphic DNA marker analysis of the blood excluded uniparental disomy 11. The female infant was normal in growth and psychomotor development during follow-ups at two months of age. Conclusion aCGH, SKY and FISH are useful in prenatal diagnosis of an sSMC derived from the centromeric region of a non-acrocentric chromosome.

Objective We present prenatal diagnosis of low-level mosaic trisomy 12. Case Report A 40-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a karyotype of 47,XX,+12[5]/46,XX[24] consistent with 17.2% (5/29) mosaicism for trisomy 12. Repeat amniocentesis performed at 21 weeks of gestation revealed a karyotype of 47,XX,+12[4]/46,XX[6] consistent with 40% (4/10) mosaicism for trisomy 12. Interphase fluorescence in situ hybridization (FISH) on 112 uncultured amniocytes detected 23 cells with trisomy 12 consistent with 20.5% (23/112) mosaicism for trisomy 12. Polymorphic DNA marker analysis excluded uniparental disomy 12. Array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed a result of arr 12p13.33q24.33 (230,451–133,773,499) × 2.2, 17p12 (14,191,925–15,442,037) × 1.0 consistent with 10–20% mosaic trisomy 12. The father carried the 17p12 microdeletion. The fetal ultrasound findings were unremarkable. A 3958-g female fetus was delivered at 37 weeks of gestation with no phenotypic abnormality. The cord blood had a karyotype of 46,XX. Postnatal interphase FISH on urinary cells revealed 7.14% (7/98) mosaicism for trisomy 12. Conclusion Low-level mosaic trisomy 12 at amniocentesis can be associated with a favorable pregnancy outcome. Interphase FISH and aCGH on uncultured amniocytes are useful for confirmation of low-level mosaic trisomy 12 at amniocentesis.

The hematopoietic stem cell-enriched miR-125 family microRNAs (miRNAs) are critical regulators of hematopoiesis. Overexpression of miR-125a or miR-125b is frequent in human acute myeloid leukemia (AML), and the overexpression of these miRNAs in mice leads to expansion of hematopoietic stem cells accompanied by perturbed hematopoiesis with mostly myeloproliferative phenotypes. However, whether and how miR-125 family miRNAs cooperate with known AML oncogenes in vivo, and how the resultant leukemia is dependent on miR-125 overexpression, are not well understood. We modeled the frequent co-occurrence of miR-125b overexpression and MLL translocations by examining functional cooperation between miR-125b and MLL-AF9 By generating a knock-in mouse model in which miR-125b overexpression is controlled by doxycycline induction, we demonstrated that miR-125b significantly enhances MLL-AF9-driven AML in vivo, and the resultant leukemia is partially dependent on continued overexpression of miR-125b Surprisingly, miR-125b promotes AML cell expansion and suppresses apoptosis involving a non-cell-intrinsic mechanism. MiR-125b expression enhances VEGFA expression and production from leukemia cells, in part by suppressing TET2 Recombinant VEGFA recapitulates the leukemia-promoting effects of miR-125b, whereas knockdown of VEGFA or inhibition of VEGF receptor 2 abolishes the effects of miR-125b In addition, significant correlation between miR-125b and VEGFA expression is observed in human AMLs. Our data reveal cooperative and dependent relationships between miR-125b and the MLL oncogene in AML leukemogenesis, and demonstrate a miR-125b-TET2-VEGFA pathway in mediating non-cell-intrinsic leukemia-promoting effects by an oncogenic miRNA.

Hypothalamic hamartoma (HH) is a congenital intracranial lesion associated with precocious puberty and gelastic epilepsy in children. Surgical management of HH to treat refractory epilepsy is a mainstay of treatment. Our aim was to compare the demographic characteristics and perioperative costs associated with resection by craniotomy and stereotactic laser ablation (SLA) by reviewing our institutional experience with SLA and comparing these data to a national database for craniotomy and resection. Retrospective chart review was conducted for the Texas Children's Hospital cohort of patients who underwent SLA for HH between 2011 and 2013. Information about the craniotomy cohort representing historical cases of craniotomy was obtained from the Kids' Inpatient Database for years 2003, 2006, and 2009. The cohort definition for patients undergoing craniotomy for HH was modified from published adult literature to identify pediatric patients with refractory epilepsy secondary to HH. Our study has shown that children undergoing SLA for HH have a shorter length of stay and lower cost of hospitalization compared with those who underwent craniotomy and resection for the same diagnosis. Together with previous findings from our institution regarding the safety and efficacy of SLA, our findings suggest that SLA may represent an attractive alternative to craniotomy for the treatment of refractory epilepsy secondary to HH.

OBJECTIVE This study aimed to examine factors associated with adherence to recommended treatment among pediatric patients with positional skull deformity by reviewing a single-institution experience (2007–2014) with the treatment of positional plagiocephaly. METHODS A retrospective chart review was conducted. Risk factors, treatment for positional head shape deformity, and parent-reported adherence were recorded. Univariate and multivariate analyses were used to assess the impact of patient clinical and demographic characteristics on adherence. RESULTS A total of 991 patients under age 12 months were evaluated for positional skull deformity at the Texas Children's Hospital Cranial Deformity Clinic between 2007 and 2014. According to an age- and risk factor–based treatment algorithm, patients were recommended for repositioning, physical therapy, or cranial orthosis therapy or crossover from repositioning/physical therapy into cranial orthosis therapy. The patients' average chronological age at presentation was 6.2 months; 69.3% were male. The majority were white (40.7%) or Hispanic (32.6%); 38.7% had commercial insurance and 37.9% had Medicaid. The most common initial recommended treatment was repositioning or physical therapy; 85.7% of patients were adherent to the initial recommended treatment. Univariate analysis showed differences in adherence rates among subgroups. Children's families with Medicaid were less likely to be adherent to treatment recommendations (adherence rate, 80.2%). Families with commercial insurance were more likely to be adherent to the recommended treatment (89.6%). Multivariate logistic regression confirmed that factors associated with parent-reported adherence to recommended treatment included primary insurance payer, diagnosis (plagiocephaly vs brachycephaly), and the nature of the recommended treatment. Families were less likely to be adherent if they had Medicaid, a child with a diagnosis of brachycephaly, or were initially recommended for cranial orthosis therapy than families with commercial insurance, a child with a diagnosis of plagiocephaly, or an initial recommendation for repositioning or physical therapy. Factors associated with treatment completion included corrected age, insurance, diagnosis, recommended treatment, and distance to provider from patient's residence. Patients with commercial insurance (OR 1.49, 95% CI 1.10–2.02, p = 0.009), those diagnosed with both brachycephaly and plagiocephaly (OR 2.26, 95% CI 1.31–3.90, p = 0.003), those recommended for treatment with cranial orthosis (OR 4.55, 95% CI = 3.24–6.38, p < 0.001), and those living in proximity to the provider (OR 1.40, 95% CI 1.00–1.96, p = 0.047) were more likely to complete treatment. CONCLUSIONS Insurance type, degree of head shape deformity, and types of recommended treatment appear to affect rates of adherence to recommended treatments for positional skull deformation.

Introduction: This study compared transsphenoidal (TS) and transfrontal (TF) approaches to craniopharyngioma utilizing a national database. Methods: The Kids' Inpatient Database (2003, 2006, and 2009) was surveyed for patients with a diagnosis of craniopharyngioma who underwent a subset of surgical interventions to compare TS and TF surgery. Demographics, hospital variables, and complications/comorbidities were analyzed with multivariate regression. Results: 314 admissions (TS = 104, TF = 210) were identified. The mean age was 14.8 (TS) versus 9.8 (TF) years (p < 0.001). The mean number of diagnoses was 4.6 (TS) versus 6.2 (TF) (p < 0.001). Diabetes insipidus was associated with 38% (TS) and 69% (TF). Cerebrospinal fluid (CSF) leak affected 19% TS and 4% TF resections. Other complications and comorbidities included postoperative stroke (2% TS vs. 5% TF), panhypopituitarism (5 vs. 8%), death (0 vs. 1%), cranial nerve deficits (1 vs. 6%), thrombotic events (7 vs. 17%), and seizures (0 vs. 12%). 98% of patients were discharged home after a mean 6-day length of stay (LOS) after TS, whereas 90% of TF patients had a LOS of 12 days. TS cases were more likely to be privately insured (68%) and from higher income brackets (61%) than TF ones (56 and 2%, respectively) (p < 0.05). In multivariate regression models adjusting for age, sex, race, number of diagnoses, surgical approach, hospital volume, and insurance type, the TS approach was associated with an increased incidence of CSF leak (OR 10, p < 0.001). More documented diagnoses (OR 16-60, p < 0.01) and TF approach (OR 2.6, p < 0.01) were associated with an increased incidence of other complications and comorbidities. Age younger than 10 (β-coefficient 2.3, p = 0.01), more diagnoses (β-coefficient 1.2, p < 0.001), and TF approach (β- coefficient 3.0, p < 0.01) were associated with increased LOS. A higher number of diagnoses were associated with nonhome discharge destinations (β-coefficient 1.29, p < 0.001). Conclusion: TS surgery was associated with an increased incidence of CSF leak but shorter LOS; TF surgery was associated with an increased incidence of other complications. Patients undergoing TS surgery were more likely to have private insurance and a higher family income bracket.

Cardiac fibrosis is the pathological consequence of fibroblast proliferation and fibroblast-to-myofibroblast transition. As a new class of endogenous non-coding RNAs, circular RNAs (circRNAs) have been identified in many cardiovascular diseases including fibrosis, generally acting as microRNA (miRNA) sponges. Here, we report that the expression of circRNA-circNFIB was decreased in mice post-myocardial infarction heart samples, as well as in primary adult cardiac fibroblasts treated with TGF-β. Forced expression of circNFIB decreased cell proliferation in both NIH/3T3 cells and primary adult fibroblasts as evidenced by EdU incorporation. Conversely, inhibition of circNFIB promoted adult fibroblast proliferation. Furthermore, circNFIB was identified as a miR-433 endogenous sponge. Overexpression of circNFIB could attenuate pro-proliferative effects induced by the miR-433 mimic while inhibition of circNFIB exhibited opposite results. Finally, upregulation of circNFIB also reversed the expression levels of target genes and downstream signaling pathways of miR-433. In conclusion, circNFIB is critical for protection against cardiac fibrosis. The circNFIB-miR-433 axis may represent a novel therapeutic approach for treatment of fibrotic diseases.

Extensive evidence has been obtained that supports an association between an attentional bias (AB) toward negative stimuli and vulnerability to mental and behavioral problems; however, diabetes self-management (DSM) behavior in type 2 diabetic patients has not specifically been assessed. The current study investigated whether type 2 diabetic Chinese patients who had different levels of self-management behaviors showed different patterns of AB toward either positive or negative stimuli. A sample of 195 patients completed questionnaires measuring DSM and a modified dot-probe task measuring AB. Patients with low levels of DSM had an avoidance bias for positive stimuli, the regression showed that negative orienting index significantly predicted lower DSM; patients with medium levels of DSM had difficulty in disengaging attention from negative stimuli, the regression showed that negative disengaging index significantly predicted lower DSM; while patients with high levels of DSM had an avoidance bias for negative stimuli and difficulty in disengaging from positive stimuli. An implication of this finding is that the understanding of information processing bias affects DSM and therefore suggests a novel target for prevention and treatment interventions.

The present study aimed to investigate the role of caprin-1 in liver cancer and its association with the clinicopathological features and prognosis of liver cancer, as well as the underlying mechanism of caprin-1 function. Caprin-1 expression levels in a tissue microarray containing 40 liver cancer tissues, 10 peritumoral tissues and 20 normal liver tissues were analyzed using immunohistochemistry. The clinical data of 154 patients with liver cancer were also collected from The Cancer Genome Atlas database. Kaplan-Meier analysis and a Cox proportional hazards regression model were used to assess the association between caprin-1 expression levels and survival in patients with liver cancer. The effects of caprin-1 knockdown on the mRNA levels of cyclin D1 and cyclin D2 as well as the proliferation, invasion and migration of HepG2 cells were also investigated. The expression level of caprin-1 in liver cancer tissues was significantly higher compared with normal liver tissues or cells (P

Background Long non-coding RNAs (lncRNAs) have been applied as biomarkers in many diseases. However, scarce biomarkers are available in single lncRNA differential expression associated with different clinical stages of liver cirrhosis (LC). The aim of the study is to identify some lncRNAs that can serve as non-invasive sensitive biomarkers for early diagnosis and grade of LC. Methods Blood lncRNA expression was evaluated in three independent cohorts with 305 participants including healthy controls, hepatitis B virus (HBV) carriers, and patients with chronic hepatitis B (CHB) or LC. First, candidate lncRNAs were screened by CapitalBiotech microarray to diagnose cirrhosis. Quantitative reverse-transcriptase polymerase chain reaction was then used to investigate the expression of selected lncRNAs in the whole group of cirrhosis and different Child–Pugh classes. Ultimately, the diagnostic accuracy of the promising biomarker was examined and validated via Mann–Whitney test and receiver-operating characteristics analysis. Results Lnc-TCL6 was identified as a sensitive biomarker for early diagnosis of LC (Child–Pugh A) compared with healthy controls (area under the ROC curve [AUC] = 0.636), HBV carriers (AUC = 0.671), and CHB patients (AUC = 0.672). Furthermore, lnc-TCL6 showed a favourable capacity in discriminating among different Child–Pugh classes (AUC: 0.711–0.837). Compared with healthy controls, HBV carriers, and CHB patients, the expression of lnc-TCL6 was obviously up-regulated in Child–Pugh A patients and, conversely, significantly down-regulated in Child–Pugh C patients. Conclusions Lnc-TCL6 is a novel potential biomarker for early diagnosis of LC and is a possible predictor of disease progression.

Introduction:FANCC is reported as a novel susceptibility gene for breast cancer, however, its mutation remains unclear in Chinese population. We aimed to identify the germline mutations of FANCC in high-risk breast cancer patients in China.Methods: 255 BRCA1/2-negative Chinese familial breast and/or ovarian cancer (FBOC) patients were recruited for FANCC germline mutations screen. For whom 90 patients were detected by PCR-sequencing assay, and another 165 patients were detected by a 98-gene panel sequencing assay. The 98-gene panel sequencing assay was also used to screen other possible gene mutations for the patients with FANCC mutations detected by PCR-sequencing assay. Two hundred and fifty sporadic breast cancer (SBC) patients and 248 female non-cancer controls (FNCCs) were recruited for the genotyping analysis. Immunohistochemistry (IHC) analysis was used to evaluate the FANCC expression in patients with FANCC mutation.Results: We found one rare FANCC deleterious mutation (c.339G>A, p.W113X, 0.4%) and two novel non-synonymous variants (c.51G>C, p.Q17H, 0.4% and c.758C>A, p.A253E, 0.4%) in FBOC patients, whereas none of above mutations was identified in SBC patients or FNCCs. We also found that one novel synonymous variant (c.903A>G, p.A301A) existed in one FBOC patient. Additionally, two non-synonymous SNPs rs201407189 (c.973G>A, p.A325T) and rs1800367 (c.1345G>A, p.V449M), and two synonymous SNPs rs55719336 (c.816C>T, p.I272I) and rs79722116 (c.1407G>A, p.T469T) were identified in FBOC patients.Conclusion:FANCC deleterious mutations exist in Chinese FBOC patients and investigations on the penetrance and spectrum of FANCC mutations need to be further conducted.

Summary: Objective: We evaluated the outcomes of laparoscopic repair of perforated peptic ulcers using simple closure only. Methods: This retrospective study included 79 patients who underwent laparoscopic repair of perforated peptic ulcers from January 2011 to February 2016. They were divided into two groups: repair with an omental patch and repair with simple closure only. All of them underwent peritoneal cavity lavage with several litres of warm normal saline. A closed suction drain system was placed for drainage of intra-abdominal abscess. Patients’ age, sex, Boey score, perforation size, operation time, overall complications, and length of hospital stay were evaluated. Results: A total of 79 patients diagnosed with perforated peptic ulcers who underwent emergency laparoscopic operations were enrolled in this study. Thirty patients underwent simple closure without an omental patch (group A), and 49 patients underwent simple closure with an omental patch (group B). Between the two groups, there were no statistically significant differences in the patients’ age, size of perforation, and Boey score. However, the operation time was significantly different (p

Background Despite documented efficacy of surgical treatment in carefully selected patients, surgery is delayed and/or underutilized in both adult and children with focal onset epilepsy. The reasons for surgical delay are often assumed or theorized, and studies have predominantly targeted the adult population. To focus on a more targeted pediatric population and to determine identifiable reasons for intervention, this study aimed to investigate time to epilepsy surgery among pediatric patients with medically intractable epilepsy associated with focal cortical dysplasia and to identify sociodemographic and clinical associations in time to epilepsy surgery. Methods We reviewed 96 consecutive pediatric patients who underwent surgery for medically intractable epilepsy with a diagnosis of focal cortical dysplasia. Descriptive statistics, univariate and multivariate analyses were conducted to study the association of sociodemographic variables of patients with focal cortical dysplasia and time to epilepsy surgery and postoperative seizure control. Results We identified that non-white patients on average had a longer duration of epilepsy before surgery and traveled shorter distances for care. Non-white patients were more likely to have government-funded insurance. Patients who traveled the shortest distance to the surgical center underwent epilepsy surgery at an older age. Conclusions Sociodemographic factors of travel distance, insurance, and race influenced time to epilepsy surgery for children with focal cortical dysplasia. Further research is warranted to target barriers in access to subspecialty care and develop ways to identify earlier the patients who may benefit from evaluation and deployment of surgical intervention.