Co-occurrence of Erdheim-Chester disease and clonally evolving acute myeloid leukemia with FLT3-ITD and PTPN11 mutations.

Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring.

Treatment and outcome of pediatric intracranial ependymoma after first relapse.

INTRODUCTION: Almost 50% of children with intracranial ependymoma experience disease relapse, and their outcomes are extremely poor. The aim of this study was to investigate optimal salvage treatment for pediatric intracranial ependymoma after the first relapse and to identify prognostic factors affecting survival. METHODS: We conducted a retrospective analysis of 159 children who underwent initial treatment for intracranial ependymoma at Beijing Tiantan Hospital from 2013 to 2017. RESULTS: Relapse was observed in 73 patients (73/159; 45.9%), with a median age of 7.2 ± 3.5 years old. Molecular subgrouping analysis identified H3K27me3-negative PF-EPNs in 74% of patients, ST-RELA EPNs in 21% of patients, and H3K27me3-positive PF-EPNs in 5% of patients. The 5-year event-free survival (EFS) and overall survival (OS) rates after first relapse were 21.1% (95% CI 16.0-26.2) and 30.5% (95% CI 19.8-30.8), respectively. Patients with GTR at first relapse had higher 5-year EFS and 5-year OS than those with STR (P = 0.031 and P = 0.003) or no surgery (P = 0.007 and P = 0.001). Radiotherapy or re-radiotherapy at first relapse significantly prolonged 5-year EFS and OS (both P < 0.001). Patients with H3K27me3-negative PF-EPN had worse 5-year EFS and OS than those with ST-RELA EPN (P = 0.001 and P = 0.002). Multivariate analysis showed that both tumor resection and radiotherapy at first relapse had independent prognostic significance for survival (all P < 0.05). CONCLUSION: Children with recurrent intracranial EPN have poor outcomes, and surgery and radiotherapy at first relapse should be encouraged to improve their prognosis.

Identification of a novel m6A-related lncRNA pair signature for predicting the prognosis of gastric cancer patients.

BACKGROUND: Accumulating studies have demonstrated that lncRNAs play vital roles in the prognosis of gastric cancer (GC); however, the prognostic value of N6-methyladenosine-related lncRNAs has not been fully reported in GC. This study aimed to construct and validate an m6A-related lncRNA pair signature (m6A-LPS) for predicting the prognosis of GC patients. METHODS: GC cohort primary data were downloaded from The Cancer Genome Atlas. We analysed the coexpression of m6A regulators and lncRNAs to identify m6A-related lncRNAs. Based on cyclical single pairing along with a 0-or-1 matrix and least absolute shrinkage and selection operator-penalized regression analyses, we constructed a novel prognostic signature of m6A-related lncRNA pairs with no dependence upon specific lncRNA expression levels. All patients were divided into high-risk and low-risk group based on the median risk score. The predictive reliability was evaluated in the testing dataset and whole dataset with receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis was used to identify potential pathways. RESULTS: Fourteen m6A-related lncRNA pairs consisting of 25 unique lncRNAs were used to construct the m6A-LPS. Kaplan-Meier analysis showed that the high-risk group had poor prognosis. The area under the curve for 5-year overall survival was 0.906, 0.827, and 0.882 in the training dataset, testing dataset, and whole dataset, respectively, meaning that the m6A-LPS was highly accurate in predicting GC patient prognosis. The m6A-LPS served as an independent prognostic factor for GC patients after adjusting for other clinical factors (p < 0.05). The m6A-LPS had more accuracy and a higher ROC value than other prognostic models for GC. Functional analysis revealed that high-risk group samples mainly showed enrichment of extracellular matrix receptor interactions and focal adhesion. Moreover, N-cadherin and vimentin, known biomarkers of epithelial-mesenchymal transition, were highly expressed in high-risk group samples. The immune infiltration analysis showed that resting dendritic cells, monocytes, and resting memory CD4 T cells were significantly positively related to the risk score. Thus, m6A-LPS reflected the infiltration of several types of immune cells. CONCLUSIONS: The signature established by pairing m6A-related lncRNAs regardless of expression levels showed high and independent clinical prediction value in GC patients.

Treatment and prognostic factors of pituicytoma: a single-center experience and comprehensive literature review.

PURPOSE: Preoperative diagnosis of pituicytomas is difficult, and management and prognostic factors remain ambiguous. The purpose of this study was to elucidate the radiological characteristics of pituicytoma, to assess the risk factors affecting tumor progression, and to propose the optimal treatment regimen based on comprehensive analysis. METHODS: We reviewed the clinical data of 22 patients with pituicytoma confirmed pathologically in our institution. In addition, 93 cases of pituicytoma in the previous literature were recruited. The individual data of 115 patients were analyzed to evaluate the adverse factors affecting pituicytoma progression. RESULTS: In the combined cohort, 3 of 61 patients who underwent gross-total resection (GTR) developed recurrence (4.9%); of the 54 patients who received non-GTR, 19 progressed (35.2%). Univariate and multivariate Cox regression analysis verified male gender (HR 2.855, 95% CI 1.008-8.089; p = 0.048), TS (transsphenoidal surgery; HR 3.559, 95% CI 1.015-12.476; p = 0.047), and non-GTR (HR 4.388, 95%CI 1.240-15.521; p = 0.022) were independent unfavorable factors for pituicytoma progression. A multivariate logistic regression model verified that tumor diameter ≥ 1.85 cm (OR 4.859, 95% CI 1.335-17.691; p = 0.016) was independent adverse factors for GTR. Compared with TS, OT (open transcranial) is more likely to have postoperative complications (OR 3.185, 95% CI 1.020-9.944; p = 0.046), especially vision deterioration (OR 37.267, 95% CI 4.486-309.595; p = 0.001). CONCLUSION: Based on our findings, GTR was advocated as an optimal treatment for pituicytomas. However, in order to avoid damage to important structures, partial resection is acceptable. After that, adjuvant radiotherapy is recommended for male patients with high Ki-67 index, and the remaining patients can be followed up closely. When the tumor recurs or progresses, it is recommended to re-operate and remove the lesion completely as far as possible. If GTR is still not possible, postoperative radiotherapy for the residual tumor is recommended.

Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation.

With treatment benefits in both the central nervous system and the peripheral system, the medical use of cannabidiol (CBD) has gained increasing popularity. Given that the therapeutic mechanisms of CBD are still vague, the systematic identification of its potential targets, signaling pathways, and their associations with corresponding diseases is of great interest for researchers. In the present work, chemogenomics-knowledgebase systems pharmacology analysis was applied for systematic network studies to generate CBD-target, target-pathway, and target-disease networks by combining both the results from the in silico analysis and the reported experimental validations. Based on the network analysis, three human neuro-related rhodopsin-like GPCRs, i.e., 5-hydroxytryptamine receptor 1 A (5HT1A), delta-type opioid receptor (OPRD) and G protein-coupled receptor 55 (GPR55), were selected for close evaluation. Integrated computational methodologies, including homology modeling, molecular docking, and molecular dynamics simulation, were used to evaluate the protein-CBD binding modes. A CBD-preferred pocket consisting of a hydrophobic cavity and backbone hinges was proposed and tested for CBD-class A GPCR binding. Finally, the neurophysiological effects of CBD were illustrated at the molecular level, and dopamine receptor 3 (DRD3) was further predicted to be an active target for CBD.

Clinical, radiological, and pathological features of 16 papillary glioneuronal tumors.

BACKGROUND: Papillary glioneuronal tumors (PGNTs) are a novel distinct intracranial neoplastic entity. In this study, the authors aimed to analyze the clinical, radiological, and pathological features of PGNT. METHODS: Clinical charts and radiographs of 16 cases of PGNT surgically treated between 2006 and 2013 were retrospectively reviewed. Follow-up evaluations and a literature review were performed. RESULTS: The study included nine males and seven females with a mean age of 23.8 years. The most common preoperative symptom was headache (68.8 %, 11 of 16 patients). Radiological results showed that the frontal lobe (25.0 %) was the most common portion of the brain involved, and 13 lesions (81.3 %) presented with cystic appearance with or without solid elements. All patients were misdiagnosed as non-PGNT tumors. Complete resection was achieved in 12 patients (75.0 %). Ki67 staining was positive in <1 % of cells present in eight lesions and varied in the other eight lesions, with a range of 1 % to 13 %. The mean follow-up duration was 56.2 months, and no recurrence was observed. Seventy-seven PGNTs (40 males, 51.9 %) have been reported, and 49 patients stained positive for Ki67/MIB-1. Of these cases, 28 (57.1 %) had positive staining rates of ≥1 %. In 51 patients for whom outcome information was available, six (11.8 %) exhibited recurrence, and the recurrence rates for complete resection and incomplete resection were 5.1 % and 33.3 %, respectively. CONCLUSIONS: PGNTs displayed a wide spectrum of clinical and radiological phenotypes, and they were more frequently observed in the frontal lobe and in young patients without sex predilection. Fair outcomes could be achieved by complete resection. Although PGNT displayed indolent pathobiology, atypical appearances were observed. More patients and longer follow-up periods are needed to further elucidate the biological features of PGNTs.

Systemic and cerebrospinal fluid biomarkers for tuberculous meningitis identification and treatment monitoring.

IMPORTANCE: Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study's findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.

[Clinicopathologic features of papillary tumors of the pineal region].

OBJECTIVE: To study the clinicopathologic features of papillary tumor of the pineal region (PTPR). METHOD: Three hundred and eighty six cases of pineal region and posterior third ventricle tumors, two newborn and two adult pineal glands were analyzed by HE, PAS and immunohistochemistry of 16 antibodies (EnVision method). RESULTS: Five cases of PTPR were diagnosed with mixed papillary features and densely cellular areas, and included one recurrent case. In the papillary areas, the vessels were lined by one or several layers of cuboidal/columnar cells; the vessel wall was hyalinized. In the densely cellular areas, sheets or nests of tumor cells were seen. The tumor cells of these five cases were immunoreactive to CK, CK8/18, synaptophysin, MAP2, nestin, S-100, and vimentin. Four cases were immunoreactive to NSE and CgA; and 2 cases were immunoreactive to NF. All five cases were negative for EMA, CK5/6, CEA, and NeuN. Ki-67 labeling index ranged from 1% to 6%.Three patients were alive, and the recurrent one died. CONCLUSIONS: PTPR occurs in patients with over a wide age range, from children to adults, and is more commonly found in male than female. PTPR is composed of both papillary and solid areas, characterized by epithelial cytology, and needs to be differentiated from ependymoma. PTPR may originate from the specialized ependymocytes of the subcommissural organ. The prognostic factors are early diagnosis, complete surgical resection and radiotherapy.

Canagliflozin alleviates high glucose-induced peritoneal fibrosis via HIF-1α inhibition.

The cardioprotective effects of sodium-glucose cotransporter type 2 (SGLT2) inhibitors have been demonstrated in many studies. However, their benefits for end-stage kidney disease patients, particularly those on peritoneal dialysis, remain unclear. SGLT2 inhibition has shown peritoneal protective effects in some studies, but the mechanisms are still unknown. Herein, we investigated the peritoneal protective mechanisms of Canagliflozin in vitro by simulating hypoxia with CoCl2 in human peritoneal mesothelial cells (HPMCs) and rats by intraperitoneal injection of 4.25% peritoneal dialysate simulating chronic high glucose exposure. CoCl2 hypoxic intervention significantly increased HIF-1α abundance in HPMCs, activated TGF-ß/p-Smad3 signaling, and promoted the production of fibrotic proteins (Fibronectin, COL1A2, and α-SMA). Meanwhile, Canagliflozin significantly improved the hypoxia of HPMCs, decreased HIF-1α abundance, inhibited TGF-ß/p-Smad3 signaling, and decreased the expression of fibrotic proteins. Five-week intraperitoneal injection of 4.25% peritoneal dialysate remarkably increased peritoneal HIF-1α/TGF-ß/p-Smad3 signaling and promoted peritoneal fibrosis and peritoneal thickening. At the same time, Canagliflozin significantly inhibited the HIF-1α/TGF-ß/p-Smad3 signaling, prevented peritoneal fibrosis and peritoneal thickening, and improved peritoneal transportation and ultrafiltration. High glucose peritoneal dialysate increased the expression of peritoneal GLUT1, GLUT3 and SGLT2, all of which were inhibited by Canagliflozin. In conclusion, we showed that Canagliflozin could improve peritoneal fibrosis and function by ameliorating peritoneal hypoxia and inhibiting the HIF-1α/TGF-ß/p-Smad3 signaling pathway, providing theoretical support for the clinical use of SGLT2 inhibitors in patients on peritoneal dialysis.

Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder.

BACKGROUND: Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. METHODS: This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. RESULTS: The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. CONCLUSIONS: The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.

Analysis of differential transcriptional profiling in wheat infected by Blumeria graminis f. sp. tritici using GeneChip.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a devastating disease of wheat. The use of wheat cultivars resistant to powdery mildew provides an effective, economical, and environmentally friendly method to control the disease. Previously, we identified a dominant resistance gene, temporarily named Pmhym, from the wheat cultivar Hongyoumai. In order to screen differential transcripts related to Pmhym-mediated resistance, four F3 homozygous resistant and four susceptible progenies derived from the Hongyoumai/Yumai13 cross were selected to construct two different pools, respectively, representing an incompatible and compatible interaction with Bgt. Pre-inoculated control and the pathogen-inoculated treatments at 24 h post inoculation (hpi) were used. Three groups of differential genes were categorized from three comparisons as pre- and post-induced, respectively, in two interactions, and post-induced between incompatible and compatible interaction. It was found that salicylic acid (SA), jasmonate (JA), and ethylene (ET) signaling-related genes were differentially expressed, thus suggesting that they are involved in the defensive response against Bgt infection. In compatible interactions, the genes involved in the abscisic acid (ABA) signaling pathway might be inhibitory to the above-mentioned three pathways, resulting in a susceptible reaction. Genes involved in disease/defense, signal transduction, and reactive oxygen species (ROS) metabolism were up-regulated in incompatible interactions, implying a role in resistant response. The results of qRT-PCR analysis on several candidate genes were consistent in their expression patterns as revealed by microarray analysis. The differential expression analyses in the present study are good candidates for further elucidation of wheat defensive response to powdery mildew.

Undifferentiated-predominant mixed-type early gastric cancer is more aggressive than pure undifferentiated type: a systematic review and meta-analysis.

BACKGROUND: Studies have shown that differentiated-predominant mixed-type early gastric cancer (EGC) is more aggressive than pure differentiated-type EGC. However, the biological behaviour of undifferentiated-predominant mixed-type (MU) EGC and pure undifferentiated-type (PU) EGC are controversial. This study was conducted to compare the biological behaviour of MU EGC and PU EGC. METHODS: A systematic review and meta-analysis of observational studies was conducted using literature published through PubMed and Embase from inception to 9 November 2021. Inclusion criteria were: (1) a direct or indirect comparison of MU and PU; (2) patients with EGC; (3) a specified outcome of lymph node metastasis (LNM), lymphovascular invasion, submucosal invasion and/or ulcer findings; and (4) the primary lesion was obtained. The literature search, data extraction and quality assessment were performed by two independent reviewers. The meta-analysis was conducted with a random-effect model using the Mantel-Haenszel method. RESULTS: Twelve publications with 5644 patients were included. Patients with MU EGC had significantly higher risk of LNM (OR 2.28; 95% CI 1.72 to 3.03) and submucosal invasion (OR 2.19; 95% CI 1.90 to 2.52) compared with patients with PU EGC. No difference was found between patients with MU and PU EGC with respect to lymphovascular invasion risk (OR 1.81; 95% CI 0.84 to 3.87). After stratifying the data according to depth of tumour invasion, a significantly higher risk for LNM was associated with intramucosal MU EGC (OR 2.56; 95% CI 1.66 to 3.95) and submucosal MU EGC (OR 2.63; 95% CI 2.06 to 3.06). Submucosal MU EGC also had a significantly higher risk of lymphovascular invasion (OR 2.40; 95% CI 1.79 to 3.21) compared with submucosal PU EGC. DISCUSSION: Patients with MU EGC had an increased risk of submucosal invasion and LNM compared with patients with PU EGC . MU patients with submucosal EGC also had an increased lymphovascular invasion risk compared with PU patients. Therefore, attention should be focused on the clinical management of patients with MU EGC.

Epidemiological characteristics of central nervous system tumors in children: a 5-year review of 3180 cases from Beijing Tiantan Hospital.

BACKGROUND: To describe the epidemiological characteristics of central nervous system (CNS) tumors in children, based on the neurosurgery department of Beijing Tiantan Hospital. METHODS: From January 2015 to December 2019, 3180 children were histopathologically diagnosed with CNS tumors based on the 2016 World Health Organization (WHO) classification of tumors. Patients were 0 to 15 years old. We analyzed age-related gender preferences, tumor locations, and the histological grades of the tumors. In addition, the epidemiological characteristics of the five most common intracranial tumors were compared to the previous studies. RESULTS: In this study, intracranial and spinal tumors account for 96.4% (3066) and 3.6% (114) of all tumors, with a preponderance of supratentorial tumors (57.9%). Among all pediatric patients, low-grade tumors comprise 67.1% (2 135). The integral gender ratio of males to females is 1.47: 1 and the average age of patients is 7.59 years old. The five most common intracranial tumors are craniopharyngioma (15.4%), medulloblastoma (14.3%), pilocytic astrocytoma (11.8%), diffuse astrocytoma (9.8%), and anaplastic ependymoma (4.8%). CONCLUSIONS: Due to the lack of national data on childhood brain tumors, we used a large nationally representative population sample based on the largest pediatric neurosurgery center in China. We analyzed the data of the past 5 years, reflecting the incidence of CNS tumors in Chinese children to a certain extent, and laying a data foundation for subsequent clinical studies.

[Clinicopathologic features of endolymphatic sac tumor at cerebellopontine angle].

OBJECTIVE: To study the clinicopathologic features and immunophenotype of endolymphatic sac tumor (ELST) and normal endolymphatic sac. METHODS: The clinical and histologic features were evaluated in 5 cases of ELST. Eight cases of choroid plexus papilloma at cerebellopontine angle and 2 cases of normal endolymphatic sac were used as controls. Immunohistochemical study for vimentin, AE1/AE3, CK8/18, CK5/6, EMA, GFAP, synaptophysin, S-100 protein, CEA, TTF-1, VEGF, D2-40, calponin, calretinin and Ki-67 was carried out. RESULTS: The age of onset of ELST ranged from 23 to 35 years (median = 24 years). The male-to-female ratio was 2:3. The clinical presentation was tinnitus, otalgia, hearing loss, otorrhagia with effusion and headache. The duration of symptoms ranged from 6 months to 10 years. Local recurrences were noted in 3 cases. Radiologically, the tumors were located at cerebellopontine angle and demonstrated petrous bone destruction. Histologic examination showed that the tumors had a papillary-glandular pattern. The papillae were covered by a single layer of low cuboidal cells. The tumor cells had distinct cell borders and contained eosinophilic to clear cytoplasm. The nuclei were slightly atypical and sometimes apically located. Focal dilated glandular structures with colloid-like material were also identified. The surrounding stroma was vascularized. All of the 5 cases had dural or petrous bone infiltration. Immunohistochemical study showed that all of the 5 cases were positive for AE1/AE3, CK8/18, CK5/6 and VEGF, 4 cases for EMA, 3 cases for calponin (focal), 2 cases for vimentin, 2 cases for S-100 protein, 1 case for GFAP and 1 case for synaptophysin (focal and weak). The Ki-67 index measured less than 1%. The staining for D2-40, calretinin, CEA and TTF-1 was negative. The 2 cases of the normal endolymphatic sac were positive for AE1/AE3 and CK8/18, and negative for CK5/6, EMA, S-100 protein, GFAP and synaptophysin. The 8 cases of choroid plexus papilloma were positive for synaptophysin. Seven cases were also positive for S-100 protein, 2 cases for GFAP and 1 case for D2-40. All of the 8 cases were negative for EMA, CK5/6 and calponin. CONCLUSIONS: ELST is a rare slow-growing and potentially malignant tumor with a tendency of bone invasion and local recurrence. Distant metastasis is not observed. It must be distinguished from choroid plexus papilloma occurring at cerebellopontine angle. Correlation with clinical, radiologic and immunohistochemical findings would also be helpful.

Incidence, predictors, and prognosis of thrombocytopenia among patients undergoing intra-aortic balloon pumping in the intensive care unit: a propensity score analysis.

OBJECTIVE: To explore the incidence, predictors, and prognosis of intra-aortic balloon pumping (IABP)-related thrombocytopenia in critically ill patients. METHODS: This multi-center study used the eICU Collaborative Research Database V1.2, comprising data on > 130,000 patients from multiple intensive care units (ICUs) in America between 2014 and 2015. A total of 710 patients undergoing IABP were included. Thrombocytopenia was defined as a drop in platelet count > 50% from baseline. From the cohort, 167 patients who developed thrombocytopenia were matched 1:1 with 167 patients who did not, after propensity score (PS) matching. The associations between IABP-related thrombocytopenia and clinical outcomes were examined by multivariable logistic regression. RESULTS: Among 710 patients undergoing IABP, 249 patients (35.07%) developed thrombocytopenia. The APACHE IVa score was a predictor of thrombocytopenia [adjusted odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.02-1.15]. After 1:1 PS matching, in-hospital mortality (adjusted OR = 0.76, 95% CI: 0.37-1.56) and in-ICU mortality (adjusted OR = 0.74, 95% CI: 0.34-1.63) were similar between the thrombocytopenia and non-thrombocytopenia groups. However, major bleeding occurred more frequently in the thrombocytopenia group (adjusted OR = 2.54, 95% CI: 1.54-4.17). In-hospital length of stay (LOS) and in-ICU LOS were significantly longer in patients who developed thrombocytopenia than in those who did not (9.71vs. 7.36, P < 0.001; 5.13 vs. 2.83, P < 0.001). CONCLUSIONS: Among patients undergoing IABP in the ICUs, thrombocytopenia was not associated with a difference in in-hospital mortality or in-ICU mortality; however, thrombocytopenia was significantly associated with a greater risk of major bleeding and increased in-ICU and in-hospital LOS.

Glycated albumin as a biomarker for diagnosis of diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Glycated albumin (GA), the non-enzymatic glycation product of albumin in plasma, became a glycemic marker in the beginning of the 21st century. The assay is not affected by hemoglobin levels and reflects the glycemic status over a shorter period as compared to HbA1c measurements. Thus, GA may contributes as an intermediate glucose index in the current diabetes mellitus (DM) diagnostic system. AIM: To search and summarize the available data on glycated albumin measurements required for the diagnosis of diabetes mellitus. METHODS: Databases, including PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL), among others, were systematically searched. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was applied for the assessment of quality, and the bivariate model was used to pool the sensitivity and specificity. The hierarchical summary receiver operator characteristic curves (HSROC) model was utilized to estimate the summary receiver operating characteristics curve (SROC). Sensitivity analysis was performed to investigate the association of the study design and patient characteristics with the test accuracy and meta-regression to find the source of heterogeneity. RESULTS: Three studies regarding gestational diabetes mellitus (GDM) and a meta-analysis of 16 non-GDM studies, comprising a total sample size of 12876, were included in the work. Results reveal that the average cut-off values of GA reported for the diagnosis of GDM diagnosis was much lower than those for non-GDM. For non-GDM cases, diagnosing DM with a circulating GA cut-off of 14.0% had a sensitivity of 0.766 (95%CI: 0.539, 0.901), specificity of 0.687 (95%CI: 0.364, 0.894), and area under the curve of 0.80 (95%CI: 0.76, 0.83) for the SROC. The estimated SROC at different GA cut-off values for non-GDM exhibited that the average location parameter lambda of 16 non-GDM studies was 2.354 (95%CI: 2.002, 2.707), and the scale parameter beta was -0.163 (95%CI: -0.614, 0.288). These non-GDM studies with various thresholds had substantial heterogeneity, which may be attributed to the type of DM, age, and body mass index as possible sources. CONCLUSION: Glycated albumin in non-DM exhibits a moderate diagnostic accuracy. Further research on the diagnostic accuracy of GA for GDM and combinational measurements of GA and other assays is suggested.

Therapeutic Strategies and Prognostic Factors Based on 121 Spinal Neurenteric Cysts.

BACKGROUND: Limited data existed to guide the management of intraspinal neurenteric cysts (ISNECs). OBJECTIVE: To evaluate the risk factors for progression-free survival (PFS), elucidate the radiological features of ISNECs, and propose a treatment protocol. METHODS: From 2003 to 2015, 121 patients with pathologically confirmed ISNECs treated at our institute were included in this study. Pertinent risk factors were evaluated. RESULTS: Gross total resection (GTR) was achieved in 55 (44.6%) patients; 106 (87.6%), 12 (9.9%), and 3 (2.5%) ISNECs were classified as Wilkins A, B, and C, respectively. After a median follow-up duration of 64.2 mo, recurrence occurred in 25 (22.7%) patients, with a median PFS time of 43.1 mo. The actuarial PFS rates at 5 and 10 yr were 73.2% and 66.2%, respectively. The actuarial overall survival rates at 5 and 10 yr were 100% and 97.6%, respectively. Non-GTR (hazard ratio [HR], 5.836; 95% confidence interval [CI], 1.698-20.058; P = .005), Wilkins B/C (HR, 3.129; 95% CI, 1.009-9.702; P = .048), and a history of surgical resection (HR, 3.690; 95% CI, 1.536-8.864; P = .004) were adverse factors. CONCLUSION: GTR and Wilkins A were favorable factors for PFS. If tolerable, GTR alone was advocated as an optimal treatment. Because of the benign nature and favorable prognosis, non-GTR was an alternative if GTR failed. Close follow-up was needed because of the recurrent tendency of ISNEC. Future study with a large cohort is necessary to verify our findings.

A transmembrane motif governs the surface trafficking of nicotinic acetylcholine receptors.

Surface expression of the nicotinic acetylcholine receptor (AChR) requires the assembly of multiple subunits in the endoplasmic reticulum (ER). Little is known, however, about the mechanism by which assembled receptor pentamers are transported to the cell membrane while unassembled subunits are retained in the ER. Here we report that a motif conserved in the transmembrane domain of AChR subunits is critically involved in this process. In COS cells, mutation within this signal allowed surface expression of unassembled subunits. Conversely, insertion of the sequence to unrelated proteins that are normally transported to the surface resulted in ER retention. The signal is buried in AChR pentamers, but is exposed on unassembled subunits in the ER, where it promotes protein degradation. We therefore conclude that this signal ensures surface trafficking of only functional AChRs.

Activation of PI3K/AKT is involved in TINAG-mediated promotion of proliferation, invasion and migration of hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy that has a poor prognosis. Through the literatures, TINAG significantly participated in the processes of the renal-associated diseases, but there were no studies about the roles of TINAG in the HCC development. Hence, we attempted to use the HCC samples collected by ourselves to reveal the clinical significance and prognostic impact of TINAG in HCC. METHODS: We first measured the expression level of TINAG in HCC on the basis of TCGA database. Then, real time quantitative reverse transcription PCR (RT-qPCR) was used to examine the expression level of TINAG in 100 pairs of HCC tissues and corresponding adjacent non-tumor tissues, as well as HCC cell lines (HepG2, HB611, HHCC, and Hep3B). Moreover, Kaplan-Meier method and COX's proportional hazards model were utilized to perform the survival and prognosis analyses using the clinical data collected by ourselves. After knockdown of TINAG, the cell proliferation, invasion and migration capacities of HepG2 and Hep3B cells were evaluate by counting kit-8 (CCK-8) assay (24 h, 48 h, 72 h, and 96 h post-cultivation), clone formation experiment, would-healing, and invasion as well as migration assays. To further explore whether the dys-regulated TINAG expression regulates the HCC progression and prognosis, protein biomarkers of PI3K signaling pathway, including AKT, p-AKT, PI3K, p-PI3K, p70S6K, and p-p70S6K were measured based on western blotting analysis. RESULTS: According to the data of TCGA database, clinical patients, and HCC cell lines, TINAG was highly expressed in HCC compared with normal. Relationship of TINAG expression level with the clinicopathological factors implicated that the high expression of TINAG was significantly associated with pathologic stage, pathologic-node, and pathologic-metastasis. Univariate as well as multivariate COX analysis indicated that TINAG expression and pathologic metastasis can serve as the independent prognostic factor for overall survival of HCC. After TINAG knockdown in HepG2 and Hep3B cells, cell proliferation rate, the colony numbers, and the invasive and migratory capacity were found to be suppressed. Remarkably, western blot results showed that reduction of TINAG remarkably decreased p-AKT, p-PI3K, and p-p70S6K expression level in HepG2 and Hep3B cells. CONCLUSION: Collectively, our results underscore the significance of TINAG in HCC progression and prognosis, and TINAG might be a novel candidate oncogene in HCC. These results propose that targeting TINAG might offer future clinical utility in HCC.

Clinicoradiological features and surgical outcomes of primary intracranial medulloepitheliomas: a single-center experience and pooled analysis of individual patient data.

OBJECTIVEMedulloepithelioma (MEPL) is a rare, malignant primitive neuroectodermal tumor with dismal survival rates. The authors aimed to define independent risk factors for progression-free survival (PFS) and overall survival (OS) and to propose an optimal treatment protocol for MEPL.METHODSThe authors reviewed the clinicoradiological data obtained in 12 patients with MEPL who underwent surgical treatment at their institution between January 2008 and June 2016. In addition, they reviewed 55 cases of MEPL published in the literature from January 1957 to July 2017. A pooled analysis of individual patient data of these 67 patients was performed to evaluate risk factors.RESULTSThe authors' cohort included 5 males and 7 females with a mean age of 15.7 years. Gross-total resection (GTR) was achieved in 10 (83.3%) patients. Radiotherapy (mean total dose 42.8 Gy) and chemotherapy were administered to 7 and 4 patients, respectively. After a median follow-up of 21.7 months, 6 (50%) patients suffered recurrence and subsequently died, with median PFS and OS times of 5.5 and 13.9 months, respectively. Among the 55 patients in the literature, 13 (23.6%) patients received GTR, and 25 (49.0%) and 15 (29.4%) received radiotherapy (median total dose 53.2 Gy) and chemotherapy, respectively. After a median follow-up of 10.0 months, the recurrence and mortality rates were 69.7% (23/33) and 70.8% (34/48), respectively, and the median PFS was 6.0 months. Of the pooled cohort, the actuarial 5-year PFS and OS were 36.3% and 29.2%, respectively, and the estimated median survival time for PFS and OS were 12.8 and 15.2 months, respectively. A multivariate Cox model verified non-GTR (HR 5.537, p < 0.001) and no radiotherapy (HR 3.553, p = 0.008) as independent adverse factors for PFS. The 5-year PFS in patients with or without GTR was 63.8% and 6.3%, respectively, and in patients with or without radiotherapy was 42.7% and 23.1%, respectively. A multivariate model demonstrated non-GTR (HR 9.089, p < 0.001), no radiotherapy (HR 3.126, p = 0.004), and no chemotherapy (HR 3.621, p = 0.004) as independent adverse factors for poor OS. The 5-year OS in patients with GTR, radiotherapy, or chemotherapy was 72.1%, 44.0%, and 58.0%, respectively. In contrast, in patients without GTR, radiotherapy, or chemotherapy, the 5-year OS was 5.8%, 14.3%, and 15.8%, respectively. Overall, in patients receiving GTR plus chemoradiotherapy, the actuarial 5-year PFS and OS were both 87.5%.CONCLUSIONSMEPL is a rare neoplastic entity with a poor prognosis. There are no distinguishing radiological features apart from cystic degeneration. Via the pooled analysis, the authors identified independent adjustable factors associated with PFS and OS, from which they advocate for GTR plus chemoradiotherapy with a sufficient dose if tolerable as an optimal treatment to improve outcomes. Future studies with large cohorts will be necessary to verify our findings.