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To evaluate the recovery of early urinary continence in patients with prostate cancer using a suprapubic catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy. From January 2018 to January 2019, 223 patients diagnosed with prostate cancer who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy in Diakonie Klinikum Stuttgart were involved in our study. From January 2018 to June 2018, patients (112 cases) only had an indwelling urinary catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy, while from July 2018 to January 2019, patients (111 cases) were offered an extra suprapubic catheter during operation. The recovery of early urinary continence of patients was mainly investigated one month later. The overall early urinary continence rate was 81.61%. Patients with suprapubic catheter had better urinary control results, compared to patients with only indwelling urinary catheter (87.39% vs 75.89%, p = 0.027). In addition, International Prostate Symptom Score and irritative subscore in patients with good urinary control were significantly lower than that in patients with urinary incontinence. Suprapubic catheter insertion (OR 0.395; 95% CI 0.190–0.821) and advanced pathological tumor stage (T3a–T4) (OR 2.061; 95% CI 1.008–4.217) were two independent influencing factors for early urinary continence recovery in patients who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy through multivariate logistic regression analysis. Suprapubic catheter insertion may be helpful for early urinary continence recovery in patients with Retzius-sparing Robotic-assistant laparoscopic prostatectomy. Advanced pathological tumor stage (T3a–T4) before Retzius-sparing robotic-assistant laparoscopic prostatectomy might be associated with poor urinary control.

Summary Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia (MPP), quantitative polymerase chain reaction (qPCR) has become a useful diagnostic method. This study was performed to explore the relationship between the qPCR findings, clinical symptoms, and inflammatory markers in children with MPP. Four hundred children with MPP have been enrolled in this retrospective analysis. All clinical and analytical information, including mycoplasma pneumoniae (MP) PCR results, has been collected. Based on the PCR results, the patients were divided into groups with load values (copy number) < 105 (54 cases), ≥105 and 108 (49 cases). The clinical features (including symptoms and signs) and inflammatory indicators were compared among the groups. The incidence of high fever (above 39°C), thermal peak during the entire hospitalization period, fever duration, days of hospitalization, and plasma lactate dehydrogenase (LDH) levels were statistically correlated with the MP PCR load value in children with MPP. The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization > duration of fever > period of hospitalization > LDH value > C-reactive protein value. The host immune response was significantly greater in the complication group than in the non-complication group.

Recent researches have showed that patients with COVID-19 pneumonia were often accompanied by pulmonary edema. Pulmonary edema is a manifestation of acute lung injury (ALI), and may progress to hypoxemia and potentially acute respiratory distress syndrome (ARDS), which have higher mortality. Precise classification of the degree of pulmonary edema in patients is of great significance for choosing the treatment plan and further improving the survival chance. In this paper, we proposed a deep learning neural network named non-local channel attention ResNet (NCA-ResNet) to analyze the lung ultrasound images and automatically score the degree of pulmonary edema in patients with COVID-19. The proposed method was designed by combining the ResNet with non-local module and the channel attention mechanism. The non-local module was used to extract the information of characteristics of A-lines and B-lines based on which the degree of pulmonary edema could be defined. The channel attention mechanism was used to assign weights to decisive channels. The data set contains 2220 lung ultrasound images provided by Huoshenshan Hospital in Wuhan, China, of which 2062 effective images with accurate scores given by two experienced clinicians were used in the experiment. The experimental results have demonstrated that our method achieved a high accuracy of classifying the degree of pulmonary edema in patients with COVID-19 by comparing with the previous deep learning methods, indicating its good potential to monitor the patients with COVID-19.

Oxidative stress-induced injury and apoptosis of human lens epithelial cells (HLECs) are early events in the development of age-related cataracts (ARCs). Humanin (HN) is a mitochondrial-related peptide that serves a cytoprotective role in various cell types and animal models. Following HN knockdown or overexpression, the level of reactive oxygen species (ROS), mitochondrial membrane potential and mitochondrial DNA copy number, cell viability, LDH activity and apoptosis of HLECs under oxidative stress were detected, and apoptosis and autophagy were detected via transmission electron microscopy. The results suggested that HN may be involved in the response of HLECs to oxidative stress, and that HN expression was significantly upregulated under oxidative stress conditions. Furthermore, exogenous HN reduced intracellular ROS content and mitochondrial damage, and enhanced mitochondrial biosynthesis; however, this protection was lost in an endogenous HN knockdown cell model. In addition, to the best of our knowledge, the present study was the first to identify that HN increased mitochondrial autophagy, which was involved in reducing ROS production under oxidative stress. The present study indicated a potential mechanism underlying the anti-oxidative damage and apoptotic effects of HN under oxidative stress. In conclusion, HN may be a potential therapeutic target for ARCs as it has a significant cellular protective effect on HLECs under oxidative stress; therefore, further study is required to investigate its role in the occurrence and development of ARCs.

The present meta-analysis was conducted to investigate the association between circulating chemerin levels and polycystic ovary syndrome (PCOS) in women.Relevant studies published up to May 2020 were searched from PubMed, Ovid, the Cochrane Library, and Clinical Trial Database. A random effects model was used to measure the strength of association between PCOS and chemerin by using the standardized mean difference (SMD) and 95% confidence interval (CI). All data were analyzed using Stata 12.0 (version 12; Stata-Corp, College Station, TX).The final meta-analysis included eight studies with 15 results including a total of 897 participants (524 patients with PCOS and 373 controls). The circulating chemerin levels were higher in patients with PCOS (random effects SMD = 1.07; 95% CI: 0.55-1.59;Our meta-analysis indicated that women with PCOS have significantly higher circulating chemerin levels than in healthy women, indicating that chemerin may be involved in the pathogenesis of PCOS.

The methods ofTraditional Chinese Medicine(TCM)'s diagnosis and treatment have undergone several changes. It is crucial to build a proper model which is capable to modernize TCM into a both standardized and individualized treatment. Tong xiao-lin proposed the state-target strategy to build a bridge for the integration of Chinese and Western medicine. It is a model based on modern medical disease concepts and using the method of TCM to balance the pathological states and adopting the achievements of pharmacology of Chinese medicine to focus on the disease targets, symptom targets, and biochemical indicator targets. The reconstruction of TCM diagnosis and treatment system for diabetes is a good example to demonstrate this theory. It could improve the clinical efficacy, support the scientific research, and reinforce the standardization of TCM.

Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. Positive and negative syndrome scale (PANSS) scores were assessed for all patients. Structural and functional brain networks were constructed using gray matter volume (GMV) and resting-state magnetic resonance imaging (rs-fMRI) time series measurements. At the connectivity level, the CSZ patients showed significantly increased SC-FC coupling strength compared with the FeSZ patients. At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.

The TCM protocol in the Diagnosis and Treatment Protocol for corona virus disease 2019 (COVID-19) (Trial Version 7) has been updated from previous versions. The protocol was formulated under the direct leadership of the National Administration of Traditional Chinese Medicine, based on the experience of a panel of experts, supported by evidence from fever clinics and from the outcomes of emergency (EM) observation rooms and inpatients throughout China (especially in Wuhan, Hubei Province) in combination with the latest scientific research results and data. The present interpretation of the TCM protocol is based on an overall understanding of the revised content, and aims to guide and standardize its clinical application to provide a reference for clinicians.

Rationale: Optic Schwannoma is rarely observed clinically as optic nerve had anatomically impossibility for the location of Schwannoma. However, several reports described the established cases of optic Schwannoma, of which the locations were in orbit or within optic canal. The occurrence of optic Schwannoma intracranially has been not reported. Patient Concerns: A 60-year-old female complained of visual impairment in the right eye and the frequent headache and the dizziness over 2 years with unknown reasons. The result of magnetic resonance imaging (MRI) showed a round, well-circumscribed, heterogeneously enhancing signal with cystic change displayed on the right suprasellar cistern. Diagnoses: Intracranial optic Schwannomas. Interventions: The patient accepted microneurosurgery assisted by endoscopy. We observed a gray and yellow lesion located near the right anterior clinoid process with a mid-sized cyst. And there was a vague boundary between the tumor and the right optic nerve which was compressed by the tumor. Optic chiasm and left optic nerve were also compressed. Meanwhile, the tumor had also adhesion to the right anterior cerebral artery (ACA). Outcomes: After the tumor was totally resected, the patient had satisfactory recovery. Lessons: We reported an intracranial optic Schwannoma removal with the lateral supraorbital keyhole approach assisted by neuroendoscopy. Intracranial optic Schwannoma was rarely seen clinically. Neuroendoscopy imaging suggested the close relationship between the tumor and ACA, supporting vasculature-origin hypothesis for the optic Schwannoma.

Corneal neovascularization (CNV) is one of the leading risk factors for vision loss. Anti-angiogenic drugs can theoretically be extended to the treatment of CNV. However, the application of these drugs is often hindered by traditional administration methods, e.g., eye drops, which is ascribed to the unique structure of the cornea and tear film. In this study, cationic polypeptide nanoparticles with mucoadhesive ability that carry lipophilic cabozantinib (a tyrosine kinase inhibitor), called Cabo-NPs, were developed for sustained cabozantinib release and inhibition of CNV. The polypeptides were synthesized via N-carboxyanhydride ring-opening polymerization and could self-assemble into micelles with cabozantinib in aqueous solution. The Cabo-NPs possessed good biocompatibility both in corneal epithelial cells and mouse corneas. More importantly, in vitro angiogenesis assays demonstrated the strong inhibitory effect of Cabo-NPs on cell migration and tube formation. Furthermore, the Cabo-NPs exerted superior anti-angiogenic effects with remarkable reductions in the neovascular area, which were as effective as the clinical dexamethasone but without apparent side effects. The therapeutic mechanism of the Cabo-NPs is closely related to the significant decrease in proangiogenic and proinflammatory factors, suppressing neovascularization and inflammation. Overall, cationic Cabo-NPs offer a new prospect for safe and effective CNV treatment via enhancing the bioavailability of lipophilic cabozantinib.

Human small intestinal crypts are the source of intestinal stem cells (ISCs) that are capable of undergoing self-renewal and differentiation to an epithelial layer. The development of methods to expand the ISCs has provided opportunities to model human intestinal epithelial disorders. Human crypt samples are usually obtained from either endoscopic or discarded surgical samples, and are thereby exposed to warm ischemia, which may impair their in vitro growth as three-dimensional culture as spheroids or enteroids. In this study we compared duodenal samples obtained from discarded surgical samples to those isolated from whole-body preserved cadaveric donors to generate in vitro cultures. We also examined the effect of storage solution (phosphate-buffered saline or University of Wisconsin [UW] solution) as well as multiple storage times on crypt isolation and growth in culture. We found that intestinal crypts were successfully isolated from cadaveric tissue stored for up to 144 h post-procurement and also were able to generate enteroids and spheroids in certain media conditions. Surgical samples stored in UW after procurement were sufficiently viable up to 24 h and also allowed the generation of enteroids and spheroids. We conclude that surgical samples stored for up to 24 h post-procurement in UW solution allowed for delayed crypt isolation and viable in vitro cultures. Furthermore, in situ, hypothermic preservation in cadaveric duodenal samples permitted crypt/ISC isolation, and successful culture of spheroids and enteroids from tissues held for up to 6 days post-procurement.

Oriented smooth muscle layers in the intestine contract rhythmically due to the action of interstitial cells of Cajal (ICC) that serve as pacemakers of the intestine. Disruption of ICC networks has been reported in various intestinal motility disorders, which limit the quality and expectancy of life. A significant challenge in intestinal smooth muscle engineering is the rapid loss of function in cultured ICC and smooth muscle cells (SMC). Here we demonstrate a novel approach to maintain the function of both ICC and SMC in vitro. Primary intestinal SMC mixtures cultured on feeder cells seeded electrospun poly(3-caprolactone) scaffolds exhibited rhythmic contractions with directionality for over 10 weeks in vitro. The simplicity of this system should allow for wide usage in research on intestinal motility disorders and tissue engineering, and may prove to be a versatile platform for generating other types of functional SMC in vitro.

Background: Opinion regarding whether Helicobacter pylori infection can promote the occurrence and development of nonalcoholic fatty liver (NAFLD) is divided. Therefore, we aimed to assess the exact relationship between H pylori infection and NAFLD by integrating all available data. Methods: The articles about H pylori infection and NAFLD were collected by searching the databases of PubMed, Embase, Web of Science, Scopus, China National Knowledge Infrastructure, and WanFang. The random-effects model was used for data analysis, followed by subgroup analysis and meta-regression to explore sources of heterogeneity. Results: Twenty-one articles were included in the study. Pooled analysis showed that H pylori infection indeed promoted NAFLD. Subgroup analysis and regression analysis showed that case-control ratio may be one of the sources of heterogeneity. Conclusions: H pylori infection is indeed one of the factors that promotes the progression of NAFLD for the Asian population. This provides new approaches for clinical prevention and treatment for NAFLD.

PCR amplification of the rrs2 gene indicated that 50% (62/124) of insectivorous bats from eastern China were infected with Leptospira borgpetersenii, L. kirschneri, and several potentially new Leptospira species. Multilocus sequence typing defined 3 novel sequence types in L. kirschneri, suggesting that bats are major carriers of Leptospira.

Purpose The aim of the study is to investigate the effects of ABCB1 , ABCC2 , UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. Methods We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. Results The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. Conclusion These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required.

Neuronal necrosis occurs during early phase of ischemic insult. However, our knowledge of neuronal necrosis is still inadequate. To study the mechanism of neuronal necrosis, we previously established a Drosophila genetic model of neuronal necrosis by calcium overloading through expression of a constitutively opened cation channel mutant. Here, we performed further genetic screens and identified a suppressor of neuronal necrosis, CG17259, which encodes a seryl-tRNA synthetase. We found that loss-of-function (LOF) CG17259 activated eIF2α phosphorylation and subsequent up-regulation of chaperons (Hsp26 and Hsp27) and autophagy. Genetically, down-regulation of eIF2α phosphorylation, Hsp26/Hsp27 or autophagy reduced the protective effect of LOF CG17259, indicating they function downstream of CG17259. The protective effect of these protein degradation pathways indicated activation of a toxic protein during neuronal necrosis. Our data indicated that p53 was likely one such protein, because p53 was accumulated in the necrotic neurons and down-regulation of p53 rescued necrosis. In the SH-SY5Y human cells, tunicamycin (TM), a PERK activator, promoted transcription of hsp27; and necrosis induced by glutamate could be rescued by TM, associated with reduced p53 accumulation. In an ischemic stroke model in rats, p53 protein was also increased, and TM treatment could reduce the p53 accumulation and brain damage.

The pharmacokinetics of Lamotrigine (LTG) varies widely among patients with epilepsy. In this study, we are aiming to investigate the effects of OCT1, ABCG2, ABCC2 and HNF4α genetic polymorphisms on plasma LTG concentrations and therapeutic efficacy in Chinese patients with epilepsy.The study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels were measured. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 were determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0.There were significant associations between OCT1 rs628031, ABCG2 rs2231142 polymorphisms and normalized LTG concentrations in patients with epilepsy (P0.05). On the other hand, polymorphisms of OCT1 rs2282143, ABCG2 rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 exhibited no correlation with LTG concentrations. Additionally, no significant association existed between all the studied genotypes and LTG treatment response.These results suggested that the polymorphisms of OCT1 rs628031 and ABCG2 rs2231142 may affect LTG metabolism in Chinese patients with epilepsy. However, future studies are necessary to be investigated in a larger cohort of epileptic patients.

Background Age-related Macular Degeneration (AMD) is the leading cause of blindness. This study aims to analyze regional differences on the global burden of AMD and help direct related policy making. Methods Disability-adjusted life years (DALY) data were collected from the Global Burden of Disease Study (GBD) 2017 to estimate the AMD burden. Mean education years, human development index (HDI) and Public Health Expenditure were extracted from the Human Development Report 2018, and latitude data were obtained from the Google Earth. These four factors were analyzed to see their importance in regional differences of AMD burden, using Kruskal-Wallis test, Dunn’s multiple comparisons test as well as regression analysis. Results Global age-standardized DALY rates have decreased since 2011. Based on the WHO region system, age-standardized DALY rates in African and Eastern Mediterranean region were significantly lower than those of other four regions. Linear regression analysis indicated that age-standardized DALY rates were inversely related to HDI and mean education years. Conclusions The age-standardized AMD burden had a decreasing tendency recently. Lower socioeconomic status and fewer education years were associated with higher AMD burden. The finding of this study may highlight the importance of national development and education on relieving AMD burden.

This study investigated the lifetime prevalence of suicide attempts (SA) and independent demographic and clinical correlates in stabilized schizophrenia inpatients. A cross-sectional study was conducted in three psychiatric hospitals in Anhui province, an agricultural province located in east China. Psychopathology and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Rating Scale (HAMD), respectively. A total of 315 stable schizophrenia inpatients were interviewed prior to discharge. The lifetime prevalence of SA was 22.2%. Multiple logistic regression analysis revealed that female gender (P

Role of surgery in the management of de novo stage IV breast cancer (BC) remains controversial. We aimed to determine the survival benefit of primary surgery on the basis of metastatic pattern.A retrospective cohort study based on the SEER database was conducted to identify patients with de novo stage IV BC diagnosed between 2010 and 2015. Patients were divided into surgery and non-surgery group, and propensity score weighting was used to balance clinicopathologic factors between groups.Of 8142 de novo stage IV BC patients, 1891 (23%) cases were managed with surgery and 6251 (77%) cases were managed without surgery. There were 3821 all-cause deaths and 3291 BC specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 54.5%, compared to 47.7% (P 0.001) for the non-surgery group. The magnitude of the survival difference with surgery was significantly correlated with metastatic patterns (PThe survival benefit offered by surgery for de novo stage IV BC varies by metastatic patterns. Decisions for primary surgery of de novo stage IV BC patients should be tailored according to metastatic pattern.

The aim of the study was to compare the oncological and functional outcomes in localized prostate cancer patients who received non-whole-gland high-intensity focused ultrasound (HIFU) with those in patients who received whole-gland HIFU therapy.Eighty-six patients from September 2012 to January 2017 in our center were retrospectively analyzed. Oncological outcomes included histological absence of prostate cancer, biochemical disease-free survival (BDFS) as well as the absence of lesions suspected for harboring prostate cancer in multiparametric magnetic resonance imaging (mpMRI). Regarding functional outcomes, we determined international prostate symptom score (IPSS), pad-free rate, pad-free and leakage-free rates as well as international index of erectile function-5 (IIEF-5).Of the 86 patients, 25 patients who underwent non-whole-gland HIFU and 61 patients who underwent whole-gland HIFU were enrolled in our 1-year follow-up study. There were no significant differences in histological absence of prostate cancer (p = 0.655), BDFS (p = 0.820), prostate-specific antigen (PSA) nadir (p = 0.453), and absence of suspicious lesions in mpMRI (p = 0.633) between non-whole-gland HIFU group and whole-gland HIFU group. However, compared with the whole-gland HIFU, the non-whole-gland HIFU group had fewer IPSS at 1 month (8.64 ± 3.63 vs 10.85 ± 6.10), a longer time to PSA nadir (5.04 ± 2.07 vs 3.83 ± 1.65), less temporary urine retention rate (20.0% vs 44.3%), less complication rate especially urinary tract strictures (4% vs 26.2%), whereas pad-free rate, pad-free and leakage-free rates, and IIEF scores were comparable.Non-whole-gland HIFU is a promising type of treatment for localized prostate cancer with satisfactory oncological results with less impairment of functional outcomes and complications compared with whole-gland HIFU, but it requires longer follow-up and larger samples of randomized control trials.

Background Objections have been raised to performing risk-reducing salpingo-oophorectomy (RRSO) to reduce disease incidence and mortality of women with BRCA mutations. We aimed to examine the relationship between RRSO and breast cancer (BC) risk and mortality with a meta-analysis. Materials and Methods We conducted a comprehensive literature search using the PubMed and Embase databases for literature published from these databases' creation to September 2017. Hazard ratio (HR) estimates were identified directly from the original articles. Pooled results were calculated on the basis of nonoverlapping studies by fixed-effect meta-analysis. Results RRSO was associated with a significant reduction in the incidence of BC in women with BRCA1/2 mutations who had no history of BC (HR = 0.58; 95% confidence interval [CI], 0.37 to 0.78). Even in women with a history of BC, RRSO could reduce the risk of recurrence (HR = 0.50; 95% CI, 0.31 to 0.69). We further found that publication year was a critical interaction factor from a corresponding subgroup analyses in BC risk (Pheterogeneity = .024). In addition, we found that RRSO could improve the survival of women with BC (HR = 0.33; 95% CI, 0.28 to 0.38). Conclusion Summary estimates presented here indicate that RRSO was closely related to the reduced risk of BC caused by BRCA mutations, but publication year was a critical interaction factor and it should be noted that more recent studies have failed to find a significant reduction in BC risk associated with RRSO.

The gap junction protein alpha 8 (GJA8) gene has been widely studied in human congenital cataracts. However, little is known about its relationship with age-related cataract (ARC). In this study, three GJA8-tagged single nucleotide polymorphisms related to an increased ARC risk were identified: rs2132397 for general ARC under both dominant and additive models; rs7541950 for general ARC under both recessive and additive models; and rs6657114 for cortical cataract under the recessive model. To uncover the underlying mechanisms, this study also sought to explore whether GJA8 is involved in the autophagy process in human lens epithelial cells. The results showed that GJA8 may participate in autophagy to maintain the intracellular environment, which may be a novel mechanism for cataract formation induced by GJA8. In conclusion, this study identified the genetic susceptibility of GJA8 polymorphisms on ARC and provides new clues for fully understanding the pathological mechanism of GJA8 variants in affecting lens opacity. Electronic supplementary material The online version of this article (10.1007/s00439-018-1945-5) contains supplementary material, which is available to authorized users.

Converging evidence has shown the link between benign epilepsy with centrotemporal spikes (BECTS) and abnormal functional connectivity among distant brain regions. However, prior research in BECTS has not examined the dynamic changes in functional connectivity as networks form. We combined functional connectivity density (FCD) mapping and sliding windows correlation analyses, to fully capture the functional dynamics in patients with respect to the presence of interictal epileptic discharges (IEDs). Resting-state fMRI was performed in 43 BECTS patients and 28 healthy controls (HC). Patients were further classified into two subgroups, namely, IED (n = 20) and non-IED (n = 23) depending on the simultaneous EEG–fMRI recordings. The global dynamic FCD (dFCD) was measured using sliding window correlation. Then we quantified dFCD variability using their standard deviation. Compared with HC, patients with and without IEDs both showed invariable dFCD (decreased) among the orbital fontal cortex, anterior cingulate cortex and striatum, as well as variable dFCD (increased) in the posterior default mode network (P

Familial cortical myoclonic tremor with epilepsy is an autosomal dominant neurodegenerative disease, characterized by cortical tremor and epileptic seizures. Although four subtypes (types 1-4) mapped on different chromosomes (8q24, 2p11.1-q12.2, 5p15.31-p15.1 and 3q26.32-3q28) have been reported, the causative gene has not yet been identified. Here, we report the genetic study in a cohort of 20 Chinese pedigrees with familial cortical myoclonic tremor with epilepsy. Linkage and haplotype analysis in 11 pedigrees revealed maximum two-point logarithm of the odds (LOD) scores from 1.64 to 3.77 (LOD scores in five pedigrees were >3.0) in chromosomal region 8q24 and narrowed the candidate region to an interval of 4.9 Mb. Using whole-genome sequencing, long-range polymerase chain reaction and repeat-primed polymerase chain reaction, we identified an intronic pentanucleotide (TTTCA)n insertion in the SAMD12 gene as the cause, which co-segregated with the disease among the 11 pedigrees mapped on 8q24 and additional seven unmapped pedigrees. Only two pedigrees did not contain the (TTTCA)n insertion. Repeat-primed polymerase chain reaction revealed that the sizes of (TTTCA)n insertion in all affected members were larger than 105 repeats. The same pentanucleotide insertion (ATTTCATTTC)58 has been reported to form RNA foci resulting in neurotoxicity in spinocerebellar ataxia type 37, which suggests the similar pathogenic process in familial cortical myoclonic tremor with epilepsy type 1.

The aim of this study was to investigate the association of depression and anxiety with adherence to antiepileptic drugs (AEDs) in Chinese patients with epilepsy.A total of 184 Chinese patients with epilepsy, and without cognitive impairment, underwent psychometric tests: the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Adherence to antiepileptic drugs was measured by the eight-item Morisky Medication Adherence Scale (MMAS-8). Data on patients' demographic characteristics, disease characteristics, and treatment characteristics were also collected.The MMAS-8 indicated that 39.7% of the patients had low adherence, 34.2% had moderate adherence, and 26.1% had high adherence. Demographic, disease, and treatment characteristics were not significantly different between the low adherence group and the moderate-to-high adherence group. Thirty-six (19.6%) patients had moderate-to-severe depression according to the BDI, and 47 (25.5%) patients were considered anxious according to the BAI. A significant difference in depression scores was found between the low adherence group and the moderate-to-high adherence group (χ(2)=13.625, P0.001). We also found a significant difference in anxiety scores between the two groups (χ(2)=8.331, P=0.004). Pearson's correlations indicated that depression scores (r=-0.281, P0.001) and anxiety scores (r=-0.255, P0.001) were negatively correlated with adherence. Negative correlations were found between BDI scores and items 2, 7, and 8 of the MMAS-8 (P0.05); negative correlations were also found between BAI scores and items 3 and 6-8 (P0.05).Depression and anxiety were associated with reduced antiepileptic drug adherence in Chinese patients. Addressing depression and anxiety among patients with epilepsy may help improve adherence to AEDs.

Objective The SELF Trial examined the effect of adding individual, self-efficacy (SE) enhancement sessions to standard behavioral weight loss treatment (SBT). Methods Participants were randomly assigned to SBT or SBT plus SE sessions (SBT+SE). Outcome measures were weight loss maintenance, quality of life, intervention adherence and self-efficacy at 12 and 18 months. Results The sample (N=130) was female (83.08%) with a mean (SD) body mass index of 33.15 (4.11) kg/m2. There was a significant time effect for percent weight change (p=.002), yet no significant group or group-by-time effects. The weight loss for the SBT+SE group was 8.38% (7.48) at 12 months and 8.00% (7.87) at 18 months, with no significant difference between the two time points (p=.06). However, weight loss for the SBT group was 6.95% (6.67) at 12 months and 5.96% (7.35) at 18 months, which was significantly different between the two time points (p=.005) indicating that the SBT group had significant weight regain. Conclusions Both groups achieved clinically significant weight loss. The group receiving an intervention targeting enhanced self-efficacy had greater weight loss maintenance whereas the SBT group demonstrated significant weight regain possibly related to the greater attention provided to the SBT+SE group.

Objective The aim of this study was to evaluate the clinical reliability and validity of the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E). Methods A total of 248 Chinese patients with epilepsy underwent psychometric tests, including the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI), the Chinese version of the Beck Depression Inventory — II (C-BDI-II), and the C-NDDI-E. Results None of the patients had difficulties understanding or completing the C-NDDI-E. Cronbach's α coefficient was 0.824. At a cutoff score of ≥ 14, the C-NDDI-E had a sensitivity of 0.854, a specificity of 0.899, a positive predictive value of 0.625, and a negative predictive value of 0.969. The scores for the C-NDDI-E were positively correlated with those for the C-BDI-II (P Conclusion The C-NDDI-E is a reliable and valid screening tool for the detection of major depression in Chinese patients with epilepsy.

To evaluate the efficacy and safety of self-retaining barbed suture (SRBS) application during laparoscopic partial nephrectomy (LPN), by assessing perioperative outcomes.Data from consecutive patients who underwent retroperitoneal LPN from January 2008 to December 2013 were retrospectively collected. Patients were divided into two groups according to suture techniques for renorrhaphy: the sliding clip technique and SRBS. The SRBS cases (Group 2 [G2]) were 1:1 matched with cases in the sliding clip group (Group 1 [G1]) for the PADUA score. Patient characteristics, perioperative outcomes, and renal function changes were compared between the groups.In total, 41 patients in G1 and 41 patients in G2 successfully underwent LPN. Patient characteristics, operative time, and complication rate were similar for both groups. Mean warm ischemia time was significantly shorter for the SRBS group (G1 versus G2, 27.5 versus 20.7 minutes; P.05). The estimated blood loss was similar in both groups. An improved early affected renal function recovery was observed in the SRBS group (percentage of glomerular filtration rate reduction for G1 versus G2, 29% versus 20.8%; P.05).The SRBS application offers an effective and safe renal parenchyma repair. In addition, SRBS appears to significantly minimize the warm ischemia injury and results in superior short-term renal function preservation.

OBJECTIVES Previous studies have reported that civilian transport is a mortality risk factor in low-resource communities. Few studies have analyzed the chief complaints associated with mortality involving civilian transport after an earthquake.Therefore, the present study was conducted to determine whether mortality resulting from medical professional transport differs from that involving civilian transport, and if so, the chief complaints associated with mortality involving civilian transport after the Wen-chuan earthquake. METHODS A hospital-based case-control study was conducted. Cases included all victims transported by civilians to West China Hospital from the disaster area (n=473). Controls included all victims transported by medical professionals to West China Hospital (n=1452). We further analyze six potential chief complaints of death to clarify the specific contributing chief complaints associated with mortality involving civilian transport. RESULTS Civilian transport is associated with significantly greater mortality compared with medical professional transport (Pearson's χ-test: P

Background Chemotherapeutic insensitivity and tumor cell invasiveness are major obstacles to effectively treating muscle-invasive bladder cancer (MIBC). Recent reports show that microRNAs (miRNAs) play an important role in the chemotherapeutic response and disease progression of MIBC. Therefore, here we investigated the role of miR-150 in MIBC cells in vitro. Material and methods miR-150 expression was quantified by qRT-PCR in two MIBC cell lines (5637 and T24). After successful miR-150 inhibition by transfection, MTS and transwell assays were used to assess the MIBC's cisplatin sensitivity and cell invasiveness, respectively. The TargetScan database and a luciferase reporter system were used to identify whether the programmed cell death 4 protein (PDCD4) is a direct target of miR-150 in MIBC cells. Results miR-150 expression was found to be significantly increased in both MIBC cell lines, and treatment with a miR-150 inhibitor significantly sensitized MIBC cells to cisplatin and inhibited MIBC cell invasiveness. PDCD4 was identified as a direct target of miR-150 in MIBC cells, and increased PDCD4 expression via transfection with the pLEX-PDCD4 plasmid efficiently sensitized MIBC cells to cisplatin chemotherapy and inhibited MIBC cell invasiveness. Conclusions This study provides novel evidence that miR-150 functions as a tumor promoter in reducing chemosensitivity and promoting invasiveness of MIBC cells via targeting PDCD4. Thus, modulation of the miR-150-PDCD4 axis shows promise as a therapeutic strategy for MIBC.

Benign epilepsy with centrotemporal spikes (BECTS) is characterized by abnormal (static) functional interactions among cortical and subcortical regions, regardless of the active or chronic epileptic state. However, human brain connectivity is dynamic and associated with ongoing rhythmic activity. The dynamic functional connectivity (dFC) of the distinct striato-cortical circuitry associated with or without interictal epileptiform discharges (IEDs) are poorly understood in BECTS. Herein, we captured the pattern of dFC using sliding window correlation of putamen subregions in the BECTS (without IEDs, n = 23; with IEDs, n = 20) and sex- and age-matched healthy controls (HCs, n = 28) during rest. Furthermore, we quantified dFC variability using their standard deviation. Compared with HCs and patients without IEDs, patients with IEDs exhibited excessive variability in the dorsal striatal-sensorimotor circuitry related to typical seizure semiology. By contrast, excessive stability (decreased dFC variability) was found in the ventral striatal-cognitive circuitry (p

The aim of this study was to determine the clinical importance and predictors of SCSs in a large population of patients with temporal epilepsy (TLE) undergoing video electroencephalographic (VEEG) monitoring. We reviewed the VEEG data of 327 consecutive patients with TLE admitted to our epilepsy center between August 2012 and January 2017. Demographic, electro-clinical, and neuroimaging data were recorded and re-analyzed. To our knowledge, this is the first study assessing SCSs recorded by long-term VEEG monitoring in patients with TLE. Twenty-seven of 327 (8.3%) patients exhibited SCSs during VEEG monitoring. Of these patients, 24 had both SCSs and clinical seizures. The mean duration of the SCSs was 23.18s (range: 5-1307s). Of the 27 patients with SCSs, 24 (88.9%) showed localizing value during the diagnostic process. Seventeen patients exhibited colocalization with clinical seizures, 4 showed useless localization related to clinical seizures, and 3 did not have clinical seizures. Sixteen patients (59.3%) experienced their first SCSs within the first 24h of monitoring and one had the first SCSs within 20min. Multivariate logistic regression analysis showed that age

The main roles of equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs) are to transfer single nucleosides and analogues for the nucleic acid salvage pathway. Oligodeoxyribonucleotides (ODNs) can be transported into the cytoplasm or nucleus of cells under certain conditions. Among ODNs composed of a single type of nucleotide, the transport efficiency differs with the length and nucleotide composition of the ODNs and varies in different types of leukaemia cells; among the 5 tested random sequence ODNs and 3 aptamers with varying sequences, the data showed that some sequences were associated with significantly higher transport efficiency than others. The transport of ODNs was sodium, energy, and pH-independent, membrane protein-dependent, substrate nonspecific for ODNs and 4-nitrobenzylthioinosine (NBMPR)-insensitive, but it showed a low sensitivity to dipyridamole (IC50 = 35.44 µmol/L), distinguishing it from ENT1-4 and CNTs. The delivery efficiency of ODNs was superior to that of Lipofection and Nucleofection, demonstrating its potential applications in research or therapeutics. Moreover, this process was associated with p38 mitogen activated protein kinase (p38MAPK) instead of c-Jun N-terminal kinase (JNK) signalling pathways. We have denoted ODN transmembrane transport as equilibrative nucleic acid transport (ENAT). Overall, these findings indicate a new approach and mechanism for transmembrane transport of ODNs.

Video-electroencephalographic monitoring (VEEG) is useful in the diagnosis of seizure disorders; however, its diagnostic yield in developing countries is not well known. The current study retrospectively reviewed the charts of 484 consecutive patients who were admitted to our center between July 2012 and September 2013. Of these patients, 298 (61.6%) were admitted for diagnostic clarification and underwent VEEG for a mean duration of 1.3days (range=1-9days). The patients were divided into two groups: those whose diagnosis was changed and those whose diagnosis was not changed as a result of VEEG. A patient with a preadmission diagnosis of epilepsy who was discharged with a diagnosis of nonepileptic events (NEEs) or who was further classified as focal/generalized epilepsy on discharge was included in the "change in diagnosis" group. A patient admitted with an uncertain diagnosis and discharged with a diagnosis of NEEs or epilepsy (including focal epilepsy and generalized epilepsy) was also included in the "change in diagnosis" group. Video-electroencephalographic monitoring recorded typical ictal events (epileptic events or nonepileptic events) in 147 (49.3%) of the patients admitted for diagnostic clarification. In total, 181 (60.7%) patients had a change in diagnosis after VEEG. Among them, 103 (56.9%) patients had a preadmission diagnosis of epilepsy, which was further classified as focal epilepsy (88 patients) or generalized epilepsy (15 patients); the diagnosis of NEEs and epilepsy was clarified in 78 (43.1%) patients. The number of patients diagnosed with NEEs increased from 31 (10.4%) on admission to 88 (29.5%) on discharge. Among all the patients admitted for diagnostic clarification, therapeutic plans were changed for 104 (57.5%) patients. In 117 (39.3%) patients with no diagnostic change, VEEG evaluation provided confirmative diagnostic information in 47 (15.8%) patients and no additional diagnostic information in 70 (23.5%) patients. The study indicates that VEEG is useful in terms of clarifying seizure diagnoses and evaluating seizure frequency. In our cohort study, VEEG of a relatively short mean duration produced a comparable diagnostic yield as that reported in other studies.

To evaluate the safety, efficacy, and potential advantages of off-clamp partial nephrectomy (OFF-PN) compared with on-clamp partial nephrectomy (ON-PN).Relevant studies comparing the safety and efficacy of OFF-PN to ON-PN were identified through a literature search using MEDLINE, EMBASE, and the Cochrane Library. The outcome measures included baseline characteristics, primary outcomes, and secondary outcomes.Ten retrospective studies (728 cases and 1267 controls) were included. No significant differences between the two groups were detected in any of the baseline variables (age: p=0.19; sex: p=0.49; BMI: p=0.29; tumor size: p=0.44, pre-eGFR: p=0.78) except for tumor location (p0.001). The OFF-PN group had a higher blood transfusion rate (odds ratio [OR] 1.54, 95% confidence interval [CI] 10.7-2.21, p=0.02), a lower postoperative complication rate (OR 0.61, 95% CI 0.44-0.83, p=0.002), and a lower positive margin rate (OR 0.49, 95% CI 0.26-0.90, p=0.02) than ON-PN. OFF-PN offered a better preservation of renal function than ON-PN (p=0.005). No significant differences were detected between the two groups in other outcomes of interest. In sensitivity analysis, there was no change in the significance of any of the outcomes except for postoperative complication rate (OR 0.91, 95% CI 0.53-1.5, p=0.73) and positive margin rate (OR 0.55, 95% CI 0.25-1.23, p=0.15).This meta-analysis suggests that with appropriate patient selection, OFF-PN offer comparable perioperative safety, equivalent oncologic outcomes, and superior long-term renal function preservation when compared with ON-PN for renal cell carcinoma. Given the inherent limitations of the included studies, future well-designed randomized controlled trials are required to confirm our findings.

As fundamental processes in mitochondrial dynamics, mitochondrial fusion, fission and transport are regulated by several core components, including Miro. As an atypical Rho-like small GTPase with high molecular mass, the exchange of GDP/GTP in Miro may require assistance from a guanine nucleotide exchange factor (GEF). However, the GEF for Miro has not been identified. While studying mitochondrial morphology in Drosophila, we incidentally observed that the loss of vimar, a gene encoding an atypical GEF, enhanced mitochondrial fission under normal physiological conditions. Because Vimar could co-immunoprecipitate with Miro in vitro, we speculated that Vimar might be the GEF of Miro. In support of this hypothesis, a loss-of-function (LOF) vimar mutant rescued mitochondrial enlargement induced by a gain-of-function (GOF) Miro transgene; whereas a GOF vimar transgene enhanced Miro function. In addition, vimar lost its effect under the expression of a constitutively GTP-bound or GDP-bound Miro mutant background. These results indicate a genetic dependence of vimar on Miro. Moreover, we found that mitochondrial fission played a functional role in high-calcium induced necrosis, and a LOF vimar mutant rescued the mitochondrial fission defect and cell death. This result can also be explained by vimar's function through Miro, because Miro’s effect on mitochondrial morphology is altered upon binding with calcium. In addition, a PINK1 mutant, which induced mitochondrial enlargement and had been considered as a Drosophila model of Parkinson’s disease (PD), caused fly muscle defects, and the loss of vimar could rescue these defects. Furthermore, we found that the mammalian homolog of Vimar, RAP1GDS1, played a similar role in regulating mitochondrial morphology, suggesting a functional conservation of this GEF member. The Miro/Vimar complex may be a promising drug target for diseases in which mitochondrial fission and fusion are dysfunctional., Author Summary Mitochondrial dynamics including fusion, fission and transport are essential for energy supply in eukaryotic cells; and defects in mitochondrial dynamics often result in premature aging and diseases such as Parkinson's disease (PD). In mitochondrial transport machinery, the Miro/Milton complex loads mitochondria onto microtubule through kinesin motor proteins; and regulates mitochondrial fusion and fission through unknown mechanisms. As a small GTPase, the exchange of GTP/GDP in Miro requires a specific guanine nucleotide exchange factor (GEF). However, the GEF for Miro has not been identified. In this study, we identified Vimar as a new regulator of mitochondrial dynamics in Drosophila. We found that loss of vimar promoted mitochondrial shortening; and this function was mediated through Miro. As a GEF, Vimar partially localized on mitochondria and could physically interact with Miro. In the pathophysiological conditions, including a Pink1 mutant to model PD and a calcium-overload induced stress to model neuronal necrosis in Drosophila, loss of vimar suppressed both aberrant mitochondrial fusion and fragmentation in PD and necrosis, respectively. As the mammalian homolog of Vimar, RAP1GDS1 function was similar to Vimar. Therefore, Vimar/ RAP1GDS1 may be a great drug target to deal with diseases caused by defective mitochondrial dynamics.

Purpose To investigate the functional connectome alterations in benign epilepsy with centrotemporal spikes with respect to the occurrence of interictal epileptic discharges (IEDs) during functional magnetic resonance (MR) imaging. Materials and Methods This prospective study was approved by the local institutional review board and was HIPAA compliant. All participants were consecutively enrolled with written informed consent. Forty-three right-handed patients were classified into IED (n = 20, 13 girls and seven boys; mean age ± standard deviation, 9.00 years ± 1.95) and non-IED (n = 23, 11 girls and 12 boys; mean age, 10.22 years ± 2.13) groups on the basis of electroencephalographic data simultaneously recorded during resting-state functional MR imaging at 3.0 T. The functional connectome features (estimated with graph theoretical analysis) in patient groups and control subjects who were matched for sex, age, and education level (n = 28, all right-handed, 13 girls and 15 boys; mean age, 10.00 years ± 2.31) were compared by using one-way analysis of variance. Results Patients with IEDs and those without IEDs showed consistently abnormal global topology in their functional networks (ie, decreased global efficiency; P.05) relative to that of control subjects, with no differences between the two patient groups (P.05). Decreased regional efficiency and connectivity strength were observed in the patients with IEDs and those without (mainly in the perirolandic and frontal areas) relative to control subjects (P.05). Moreover, the altered functional features significantly correlated with clinical characteristics (ie, disease duration and age at symptom onset, P.05). Conclusion These findings suggest that decreased global and regional efficiency are prominent functional deficits in children with benign epilepsy with centrotemporal spikes and can be readily identified with resting-state functional MR imaging, irrespective of IEDs.

Purpose Glioneuronal tumors (GNTs) are the most common histological type of brain tumors in patients who received epilepsy surgery, and part of them presented with BRAF V600E mutation. We aimed to verify the presence of the BRAF V600E mutation in epilepsy-associated GNTs from Chinese population and evaluate the association with clinical features. Methods Data from 35 patients diagnosed with GNTs, including 24 gangliogliomas and 11 dysembryoplastic neuroepithelial tumors, were retrospectively collected. DNA was extracted from GNTs tissues and BRAF V600E mutation was examined by DNA sequencing. The correlations between BRAF V600E mutation and clinical features were analyzed. Results Totally, BRAF V600E mutations were detected in 11 patients with GNTs, the rate of mutation were 33.3% and 27.3% in GGs (8/24) and DNTs (3/11), respectively. The probability of BRAF V600E mutation in females (7/12, 58.3%) was significantly higher than that in males (4/23, 17.4%) (P=0.022). Moreover, patients with BRAF-mutated GNTs had a significantly wider variety of seizure types compared to GNTs with BRAF wild-type status (P=0.027). However, no significant correlation between the BRAF status and certain clinical features, such as age of seizure onset, duration of epilepsy, age at surgery, location of the tumor and postoperative seizure free, were observed. Conclusion We demonstrated the presence of BRAF V600E mutation in Chinese epileptic patients with GNTs, which was significantly correlated with gender and multiple seizure types. Large sample studies and long-term follow-up are required for further confirmation.

OBJECTIVE To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis. RESEARCH DESIGN AND METHODS We enrolled 28 patients with type 1 diabetes, aged 14–30 years, in a prospective AHSCT phase II clinical trial. HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin. Changes in the exogenous insulin requirement were observed and serum levels of HbA1c, C-peptide, and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT. RESULTS After transplantation, complete remission (CR), defined as insulin independence, was observed in 15 of 28 patients (53.6%) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months. The non-DKA patients achieved a greater CR rate than the DKA patients (70.6% in non-DKA vs. 27.3% in DKA, P = 0.051). In the non-DKA group, the levels of fasting C-peptide, peak value during oral glucose tolerance test (Cmax), and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up (all P < 0.05). In the DKA group, significant elevation of fasting C-peptide levels and Cmax levels was observed only at 18 and 6 months, respectively. There was no mortality. CONCLUSIONS We have performed AHSCT in 28 patients with type 1 diabetes. The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis.

Background & Aims Intestinal microfold (M) cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer’s patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs), and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting. Methods Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium. Results Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2) in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells. Conclusions Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an in vitro setting. We anticipate that this model can be used to generate large numbers of M cells for further functional studies of these key cells of intestinal immune induction and their impact on controlling enteric pathogens and the intestinal microbiome.

Upper urinary-tract urothelial carcinomas (UTUC) constitute 5% of urothelial malignancies. Prognostic biomarkers would allow lower risk surgical approaches for less aggressive UTUCs. One biomarker-Ki-67/mindbomb E3 ubiquitin protein ligase 1 (Ki-67/MIB-1)-shows promise in UTUC, but there have been conflicting findings regarding its prognostic role. The systematic review and meta-analysis aim to determine the prognostic value of Ki-67/MIB-1 in UTUC in terms of UTUC-specific mortality rate, 5-year disease-free survival, and 5-year overall survival (including disease-specific survival).A systematic review of the current literature produced 654 records. A total of 13 studies consisting of 1030 patients were finally included in the meta-analysis. Hazard ratios (HRs) with 95% confidence intervals (CI) were extracted or estimated. The individual HR estimates were combined into a pooled HR using a fixed-effects model that summed homogeneity of the individual true HRs.Patients with Ki-67/MIB-1 overexpression displayed significantly higher UTUC-specific mortality rate (pooled HR: 2.14, 95% CI: 1.73-2.64; p0.00001), significantly reduced 5-year disease-free survival (pooled HR: 2.27, 95% CI: 1.79-2.92; p0.00001), and significantly reduced 5-year overall survival (pooled HR=1.77; 95% CI: 1.39-2.23 p0.00001). There was significant heterogeneity detected in the UTUC-specific mortality rate meta-analysis (I(2)=63%) and the 5-year disease-free survival meta-analysis (I(2)=65%), but there was no significant heterogeneity detected in the 5-year overall survival meta-analysis (I(2)=0%). Egger's testing showed that none of the outcomes were influenced by publication bias (p0.05).Ki-67/MIB-1 overexpression shows promise as a prognostic biomarker for UTUC patients and requires further investigation.

Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting‐state functional magnetic resonance imaging (RS‐fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age‐matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS‐fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878–3889, 2015. © 2015 Wiley Periodicals, Inc.

To investigate the patients' characteristics and efficacy of prognosis evaluation by International Prognosis Scoring System (IPSS) and Revised International Prognosis Scoring System (IPSS-R) in patients with myelodysplastic syndrome (MDS).Prognostic value of IPSS and IPSS-R was evaluated on clinical data from 159 MDS patients, according to WHO classification.With a median age of 44 years (range:15-80 years), MDS patients had the frequency of 38.56% with abnormal karyotype, including the most common abnormality +8 (20/153, 12.6%). 34 of 142 patients transformed into leukemia. Age and the level of β2 micro-globulin were the prognostic factors by multivariate analysis and IPSS-R had a better prognostic significance. The differences in cumulative survival between IPSS subgroups were significant (P0.05) except that between low- and intermediate I-risk group (P0.05). There were statistical differences for IPSS-R low risk group vs high or very high risk group, and intermediate risk group vs high or very high risk group (P0.05). IPSS-R enables IPSS subgroups re-stratification and split IPSS intermediate I-risk group into two subgroups with different prognosis.There were significant differences in age of onset, distribution of prognosis scoring system subgroups and abnormal karyotype compared with those in Europe and America. The proportion of higher risk (worse than good karyotype) in IPSS-R was higher than that in Europe and America. Age and the level of β2 micro-globulin were prognostic factors. Both IPSS and IPSS-R were applicable in Chinese MDS patients and the latter performed better. Applying IPSS-R to re-stratify IPSS subgroups helps evaluate prognosis more accurately and improve treatment outcomes.

Benign epilepsy with centrotemporal spikes (BECTS) is a common childhood epilepsy syndrome associated with abnormalities in neurocognitive domains, particularly during interictal epileptiform discharges (IEDs). Here, we investigated the effects of IEDs on brain’s intrinsic connectivity networks in 43 BECTS patients and 28 matched healthy controls (HCs). Patients were further divided into IED and non-IED subgroups based on simultaneous EEG-fMRI recordings. Functional connectivity within and between five networks, corresponding to seizure origination and cognitive processes, were analyzed to measure IED effects. We found that patients exhibited increased connectivity within the auditory network (AN) and the somato-motor network (SMN), and decreased connectivity within the basal ganglia network and the dorsal attention network, suggesting that both transient and chronic seizure activity may disturb normal network organization. The IED group showed decreased functional connectivity within the default mode network (DMN) compared with the non-IED group and HCs, implying that the DMN was selectively impaired during epileptiform discharges associated with altered self-referential cognitive functions. Moreover, the IED group exhibited increased positive correlations between the AN and the SMN, which suggests a possible excessive influence of centrotemporal spiking on information processing in the auditory system. The association between epileptic activity and network dysfunctions highlights their importance in investigating the pathological mechanism underlying BECTS.

Children with rolandic epilepsy (RE) are often associated with cognitive deficits and behavioral problems. Findings from neurophysiological and neuroimaging studies in RE have now demonstrated dysfunction not only in rolandic focus, but also in distant neuronal circuits. Little is known, however, about whether there is distributed abnormal spontaneous brain activity in RE. Using resting-state functional magnetic resonance imaging (RS-fMRI), the present study aimed to determine whether children with RE show abnormal local synchronization during resting state and, if so, whether these changes could be associated with the behavioral/clinical characteristics of RE. Regional homogeneity (ReHo) in children with RE(n=30)and healthy children(n=20)was computed on resting-state functional MRI data. In comparison with healthy children, children with RE showed increased ReHo in the central, premotor, and prefrontal regions, while they showed decreased ReHo in bilateral orbitofrontal cortex and temporal pole. In addition, the ReHo value in the left orbitofrontal cortex negatively was corrected with performance intelligence quotient in the children with RE. The aberrant local synchronization, not strictly related to primary site of the typical rolandic focus, indicates the neuropathophysiological mechanism of RE. The study findings may shed new light on the understanding of neural correlation of neuropsychological deficiencies in the children with RE.

Objective: This study presents our initial experience with extraperitoneal and transperitoneal laparoscopic partial cystectomy (LPC) in the treatment of benign non-urothelial bladder tumors. Methods: Eleven patients with benign non-urothelial bladder tumors underwent extraperitoneal or transperitoneal LPC. The five cases with tumors located on the anterior/anterolateral bladder wall received the extraperitoneal approach. The six cases with tumors located around the bladder dome or over the posterior bladder wall received the transperitoneal approach. Key perioperative parameters were recorded. Results: All patients underwent laparoscopic resection smoothly without requiring a conversion to a traditional open procedure, and no patient displayed perioperative complications. Pathology showed benign non-urothelial bladder tumors with normal margins in all eleven patients, including five leiomyoma cases, three pheochromocytoma cases, two paraganglioma cases and one inflammatory fibrous histiocytoma case. Follow-up cystoscopy and imaging studies in all eleven patients (mean follow-up period 32 months) revealed neither residual nor local recurrence. Conclusions: LPC is safe and feasible in select patients with benign non-urothelial bladder tumors and yields satisfactory oncological and functional results. Extraperitoneal LPC should be preferred for lesions located on the anterior/anterolateral bladder wall, while transperitoneal LPC should be preferred for lesions around the bladder dome or over the posterior bladder wall.

Vitamin D receptor (VDR) plays a key role in calcium metabolism, and is closely related to urinary stone formation (urolithiasis). Previous studies have investigated the associations between VDR single nucleotide polymorphisms (SNPs) (polymorphisms at BsmI, ApaI, FokI, or TaqI cutting sites) and urolithiasis in different populations. However, the results remain inconsistent and controversial. Therefore, meta-analysis was performed to evaluate these associations. Twenty studies that investigated the associations between VDR SNPs and urolithiasis were retrieved. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated under the most appropriate genetic model. The TaqI polymorphism was associated with an increased risk of urolithiasis (tt + Tt vs. TT: OR = 1.253; 95 % CI = 1.033–1.520, p = 0.022, I2 = 0), whereas the ApaI, BsmI, and FokI polymorphisms were not. Stratifying for ethnicity, a slightly increased risk was found among Asians as compared to Whites (OR 1.263, 1.232, respectively, p < 0.01). Deviation from Hardy–Weinberg equilibrium (HWE) was the major source of heterogeneity. In summary, this updated meta-analysis suggests the TaqI polymorphism is associated with urolithiasis risk, whereas BsmI, ApaI, and FokI polymorphisms are not.