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Bromadiolone, a widely-used rodent control drug, could act as a long-acting anticoagulant. Patients of bromadiolone poisoning often present with multiorgan hemorrhage. However, neurological symptoms of bromadiolone poisoning are seldom reported. We report a rare case with convulsive status epilepticus as the initial presentation of bromadiolone poisoning. A previously healthy 18-year-old man presented with persistent unconsciousness and repeated convulsive seizures. Magnetic resonance imaging revealed lesions in the corpus callosum. Laboratory test revealed the microscopic hematuria, prolonged prothrombin time, prolonged activated partial thromboplastin time and the presence of bromadiolone. The patient was diagnosed as the bromadiolone poisoning and treated with hemofiltration, vitamin K and prothrombin complex. Consciousness of the patient was regained and all neurological symptoms diminished after 7 days. Coagulopathy was totally corrected after 3 weeks, and a 2-month regimen of vitamin K supplementation was prescribed after discharge. Our case suggests that bromadiolone poisoning may involve the central nervous system. The atypical and initial symptoms of neurological disorders might lead to misdiagnosis of bromadiolone poisoning. Poisoning should be considered when acute neurological symptoms are combined with bleeding tendency. The vitamin K treatment is effective for both coagulopathy and central nervous system disorders in bromadiolone poisoning.

The search for therapeutic targets for Parkinson’s disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.

Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

Axonal variants of Guillain-Barre syndrome (GBS) mainly include acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and pharyngeal-cervical-brachial weakness. Molecular mimicry of human gangliosides by a pathogen's lipooligosaccharides is a well-established mechanism for Campylobacter jejuni-associated GBS. New triggers of the axonal variants of GBS (axonal GBS), such as Zika virus, hepatitis viruses, intravenous administration of ganglioside, vaccination, and surgery, are being identified. However, the pathogenetic mechanisms of axonal GBS related to antecedent bacterial or viral infections other than Campylobacter jejuni remain unknown. Currently, autoantibody classification and serial electrophysiology are cardinal approaches to differentiate axonal GBS from the prototype of GBS, acute inflammatory demyelinating polyneuropathy. Newly developed technologies, including metabolite analysis, peripheral nerve ultrasound, and feature selection via artificial intelligence are facilitating more accurate diagnosis of axonal GBS. Nevertheless, some key issues, such as genetic susceptibilities, remain unanswered and moreover, current therapies bear limitations. Although several therapies have shown considerable benefits to experimental animals, randomized controlled trials are still needed to validate their efficacy.

The prognostic significance of d-dimer level in patients with coronary artery disease (CAD) is not fully established. This meta-analysis aimed to examine the association between elevated d-dimer level at baseline and adverse outcomes in patients with CAD. Two independent authors comprehensively searched PubMed and Embase databases from their inception to December 31, 2020. All observational studies reporting the values of baseline d-dimer level in predicting the major adverse cardiovascular events (MACEs) or survival outcomes in patients with CAD were included. The prognostic values were calculated by pooling adjusted RR with 95% CI for the highest versus the lowest d-dimer level. Thirteen studies consisting of 25 600 patients with CAD were identified. Comparison between the highest and lowest d-dimer level showed that the pooled multivariable adjusted RR was 1.69 (95% CI, 1.53-1.86) for all-cause mortality, 2.37 (95% CI, 1.52-3.69) for cardiovascular mortality, and 1.44 (95% CI, 1.19-1.74) for MACEs, respectively. Elevated blood level of d-dimer at baseline was independently associated with higher risk of MACEs, cardiovascular death, and all-cause mortality in patients with CAD. The baseline d-dimer level may have important prognostic value in patients with CAD.

The COVID-19 pandemic, caused by SARS-CoV-2 infection, remains a dramatic threat to human life and economic well-being worldwide. Significant heterogeneity in the severity of disease was observed for patients infected with SARS-CoV-2 ranging from asymptomatic to severe cases. Moreover, male patients had a higher probability of suffering from high mortality and severe symptoms linked to cytokine storm and excessive inflammation. The NLRP3 inflammasome is presumably critical to this process. Sex differences may directly affect the activation of NLRP3 inflammasome, impacting the severity of observed COVID-19 symptoms. To elucidate the potential mechanisms underlying sex based differences in NLRP3 activation during SARS-CoV-2 infection, this review summarizes the reported mechanisms and identifies potential therapeutic targets.

To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307–0.567)]. A longer duration of CM therapy (6–12 months, 12–18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I–IIIA (HR=0.50, 95% CI: 0.37–0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33–0.71), DFS was even longer among CM treatment group patients. Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398)

INTRODUCTION In recent years, everolimus-eluting bioresorbable vascular scaffold stents (EE-BRS) were developed as alternative to everolimus-eluting metallic stents (EES) for coronary artery disease (CAD) treatments. Areas covered: Searches were conducted in MEDLINE, EMBASE, EBSCO, Springer, Ovid, TCTMD, Cardiosource, Clinical Trial Results and the Cochrane Library with combined key words such as bioresorbable vascular scaffold (BVS), everolimus-eluting metallic stents, EES, coronary artery disease, CAD and randomized-Controlled Trials.Finally, 5,474 patients were enrolled for comparison of device-induced thrombosis, ischemia-driven target lesion revascularization (ID-TLR), device-oriented composite endpoints (DOCE), patient-oriented composite endpoints (POCE), and target vessel failure (TVF) between EE-BRS and EES treatments. The primary literature search retrieved 200 records. Expert Opinion: There was no difference regarding DOCEs, POCEs and ID-TLRs for 1 or 2 years, whereas there were significant differences regarding thrombosis between EE-BRS and EES interventions in the 1-year (pooled HR, 2.15, 95%CI: 1.11, 4.18) and 2-year follow-ups (pooled HR, 2.02, 95%CI: 1.08, 3.78), but not in the 3-year follow-up (pooled HR, 1.57, 95%CI: 0.66, 3.75) anymore. The results of this study showed no inferiority of EE-BRS regarding TVF, DOCE, POCE and ID-TLR 1-year and 2-years after interventions, but enhanced risk of thrombosis in the EE-BRS patients, which disappeared in 3-year follow-ups.

Background Cyclin-dependent kinases (CDKs) are regarded as promising targets for cancer therapy. CDK2 and CDK4 are the core molecules in the G0 and G1 phases of the cell cycle. Exploring the molecular mechanism of CDK2 and CDK4 protein degradation will provide clues and solutions to control the G0 and G1 phases in tumor cells. Methods The expression levels of CDK2 and CDK4 were assessed by Western blotting and qRT-PCR. Cell viability, cell proliferation and growth were evaluated in CCK-8 and flow cytometric analysis. Protein interactions were analysed by immunoprecipitation and immunofluorescence methods. Results NVP-BEZ235 induced neuroblastoma cell arrest at the G0/G1 phase, and proliferation inhibition was associated with a significant reduction in the CDK2 and CDK4 proteins in a dose-dependent manner at nanomolar concentrations. Surprisingly, we found that the NVP-BEZ235-induced downregulation of CDK2 and CDK4 was dramatically rescued by autophagy-lysosome inhibitors. Additionally, the blockade of autophagy-related genes contributed to the remarkable rescue of CDK2 and CDK4, which thus strikingly improved NVP-BEZ235-induced G0/G1 arrest and growth inhibition of neuroblastoma cells. Subsequently, we observed the first evidence that NVP-BEZ235 induced the interaction of p62/SQSMT1 with CDK2 or CDK4 and the autophagic degradation of CDK2 and CDK4 in a cathepsin B-dependent manner. Analogous results regarding autophagy and the antiproliferative effects of NVP-BEZ235 were observed in a neuroblastoma xenograft mouse model in vivo. Conclusions These results not only established the pivotal role of the autophagy pathway in G0/G1 cell cycle-related protein turnover but also suggest the potential application of NVP-BEZ235 for cancer treatment by modulating elements of the autophagic machinery to promote degradation of G0/G1 cell cycle-related proteins.

Introduction: Up to 30% of patients with Guillain-Barre syndrome (GBS) develop respiratory failure requiring intensive care unit (ICU) admission and mechanical ventilation. Progressive weakness of the respiratory muscles is the leading cause of acute respiratory distress and respiratory failure with hypoxia and/or hypercarbia. Bulbar weakness may compromise airway patency and predispose patients to aspiration pneumonia. Areas covered: Clinical questions related to the use of mechanical ventilation include but are not limited to: When to start? Invasive or noninvasive? When to wean from mechanical ventilation? When to perform tracheostomy? How to manage complications of GBS in the ICU including nosocomial infection, ventilator-associated pneumonia, and ICU-acquired weakness? In this narrative review, the authors summarize the up-to-date knowledge of the incidence, pathophysiology, evaluation, and general management of respiratory failure in GBS. Expert opinion: Respiratory failure in GBS merits more attention from caregivers. Emergency intubation may lead to life-threatening complications. Appropriate methods and time point of intubation and weaning, an early tracheostomy, and predictive prophylaxis of complications benefit patients' long-term prognosis.

Guillain–Barré syndrome (GBS) is an acute polyneuropathy mostly characterized by acute flaccid paralysis with or without sensory/autonomous nerve dysfunction. Current immuno therapies including intravenous immunoglobulin (IVIg), plasma exchange (PE), and newly developed biological drugs benefit patients by alleviating hyperreactive immune responses. Up to 30% of patients develop respiratory failure during hospitalization and require mechanical ventilation and intensive care. Immunotherapies, mechanical ventilation, supportive care, and complication management during the intensive care unit (ICU) stay are equally emphasized. The most important aspect of intensive care and treatment of severe GBS, that is, mechanical ventilation, has been extensively reviewed elsewhere. In contrast to immunotherapies, care and treatment of GBS in the ICU setting are largely empirical. In this review, we intend to stress the importance of intensive care and treatment, other than mechanical ventilation in patients with severe GBS. We summarize the up-to-date knowledge of pharmacological therapies and ICU management of patients with severe GBS. We aim to answer some key clinical questions related to the management of severe GBS patients including but not limited to: Is IVIg better than PE or vice versa? Whether combinations of immune therapies benefit more? How about the emerging therapies promising for GBS? When to perform tracheal intubation or tracheostomy? How to provide multidisciplinary supportive care for severe cases? How to avert life-threatening complications in severe cases?

Several severity scales have been documented to predict the short-term mortality of septic patients. However, the predictive efficacies of different severity scales in the long-term mortality of the elderly have yet to be evaluated.In the retrospective study, a cohort of 4,370 elderly (≥65 years) septic patients admitted to the intensive care unit (ICU) were divided into three different age groups, i.e., the younger-old group (65 years ≤ age75 years), the older-old group (75 years ≤ age85 years) and the oldest-old group (age ≥85 years). Five scales, including the Simplified Acute Physiology Score II (SAPS II), the Oxford Acute Severity of Illness Score (OASIS), the Modified Logistic Organ Dysfunction System (MLODS), the Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA), were used for disease severity evaluations. The Kaplan-Meier survival curve, and the area under the receiver operating characteristic curve (AUC) were used to assess prognostic values of the long-term mortality of each severity scale.Compared with patients in the oldest-old group, those in the younger-old and the older-old groups had higher scores of SAPS II and OASIS, indicating more serious illness and worse prognosis. The survival time of patients was inversely related to age; the mean survival time was the longest in the youngerold group, followed by the older-old group and the oldest-old group. SAPS II had the best prognostic value (AUC: 0.648 for SAPS II, 0.579 for MLODS, 0.577 for SOFA, 0.612 for OASIS and 0.515 for SIRS, P0.01) for the 4-year all-cause mortality. Elderly patients with an SAPS II score43 had a lower survival rate regardless of age.The long-term mortality of elderly patients with sepsis is increased with age. SAPS II can better predict the long-term prognosis of elderly septic patients in ICU.

Hypertensive encephalopathy (HE) is a subset of posterior reversible encephalopathy syndrome. It typically involves the posterior supratentorial structures, but variations do occur. However, isolated brainstem involvement in HE is rare, with a few cases reported in the literature. Herein, we report a case of acute hypertensive brainstem encephalopathy in which the patient had mild symptoms with very high blood pressure and normal neurological examination. The computed tomography of the brain showed diffuse hypodensity at brainstem. The patient's symptoms improved drastically after hypertension had been controlled. Marked clinical-radiologic dissociation in this particular case was highly suggestive of hypertensive brainstem encephalopathy. Prompt recognition of the condition and aggressive treatment of hypertension in such patients is crucial to relieve oedema and to prevent life-threatening progression. Nevertheless, there is still a lack of awareness among physicians and radiologists regarding this rare clinical entity.

IntroductionThe aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN).Material and methodsWe selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 µg P0 peptide 180–199 emulsion in 25 µl of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 µl of Freund’s incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit.ResultsWe found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-γ, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts.ConclusionsBased on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.

The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P < 0.05). Group B patients had the lowest clinical pregnancy, implantation, and live birth rates of all groups (P < 0.05). No differences were found in the miscarriage rate or birth defects among the groups (P > 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.

Acute kidney injury (AKI) is a serious complication in the intensive care unit (ICU), which may increase the mortality of critically ill patients. The red blood cell distribution width (RDW) has proved useful as a predictor of short-term prognosis in critically ill patients with AKI. However, it remains unknown whether RDW has a prognostic value of long-term all-cause mortality in these patients. The data of 18279 critically ill patients with AKI at first-time hospital admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The tertiles of the RDW values were used to divide subjects into three groups, namely RDW

BACKGROUND: Renal anemia is a severe complication of chronic kidney disease (CKD) and may worsen its prognosis. Roxadustat is the only oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that has been proved effective to treat renal anemia. However, effects of roxadustat on non-dialysis-dependent CKD (NDD-CKD) have yet to be supported by evidence-based medicine. METHODS: Based on the databases of PubMed, EMBASE and Web of Science by 12 April 2019 (CRD42019133225), a meta-analysis of randomized controlled trials (RCTs) on roxadustat for treatment of NDD-CKD was conducted. Primary outcomes were parameters of hemoglobin (Hb) and Hb response. Secondary outcomes were hepcidin, ferritin, total iron binding capacity (TIBC), transferrin saturation (TAST), incidences of diarrhea, adverse events (AEs) and severe adverse events (SAEs). The risk of bias and the quality of evidence were assessed, respectively. Both continuous and binary variables were analyzed by the random effects models. Sensitivity analyses were performed when a significant heterogeneity was observed (P50%). RESULTS: Finally, three studies with a total of 214 subjects in the roxadustat group and 80 subjects in the placebo group were enrolled. An increase of Hb [weighted mean difference (WMD) =1.22, 95% CI: 0.95 to 1.49, P

Macrophage migration inhibitory factor (MIF) plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN), which may offer an opportunity for the development of the novel therapeutic strategies for GBS. Areas covered: 'macrophage migration inhibitory factor' and 'Guillain-Barré syndrome' were used as keywords to search for related publications on Pub-Med, National Center for Biotechnology Information (NCBI), USA. MIF is involved in the etiology of various inflammatory and autoimmune disorders. However, the roles of MIF in GBS and EAN have not been summarized in the publications we identified. Therefore, in this review, we described and analyzed the major roles of MIF in GBS/EAN. Primarily, this molecule aggravates the inflammatory responses in this disorder. However, multiple studies indicated a protective role of MIF in GBS. The potential of MIF as a therapeutic target in GBS has been recently demonstrated in experimental and clinical studies, although clinical trials have been unavailable to date. Expert opinion: MIF plays a critical role in the initiation and progression of GBS and EAN, and it may represent a potential therapeutic target for GBS.

To evaluate and compare left and right testicular tissue histopathology and Johnsen score, and to investigate the necessity for bilateral testicular biopsy. We recruited180 patients with non-obstructiveazoospermia (NOA) on testicular biopsy who had undergonetesticular sperm aspiration (TESA). Pathological sections of testicular tissue were diagnosed by specially-assigned doctors, who evaluated pathological findings, determined the Johnsen score and confirmed for the presence or absence of sperm. Sperm positive rates for left and right testicular histopathology were 55.0% and 51.7% respectively, and the proportion of Johnsen scores≥8 for left and right testes were 53.3% and 50.0%, respectively. Cohen kappa values revealed that the identification of sperm in bilateral testicular samples was not consistent and was related to random effects; Optimized cut-off value for bilateral testicular volume was 11ml (Johnsen score ≥8), and optimized cut-off values of E2 on left and right testes were 144.5pmol/L and 133.5 pmol/L (Johnsen score≤7). However, age, serum prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone (TT) levels were not accurate predictors for the existence of testicular sperm. There was nostatistical significance between left and right testicular histopathology in terms of sperm positive rates or Johnsen score; the Johnsen score were caused entirely by random effects and a score from one side could not represent the other side. Therefore, we recommend that both testes need to undergo surgery when NOA patients undergo testicular biopsy or sperm retrieval.

Background/Aims: Dysbiosis of the intestinal microbiota may accelerate the progression of chronic kidney disease (CKD) by increasing the levels of urea toxins. In recent years, probiotics have been recognized to maintain the physiological balance of the intestinal microbiota. In this study, we aim to assess the therapeutic effects of probiotics on CKD patients with and without dialysis via meta-analysis. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) by searching the databases of Pubmed, EMBASE and Cochrane Library (No. CRD42018093080). Studies on probiotics for treatment of CKD adults lasting for at least 4 weeks were selected. The primary outcomes were the levels of urea toxins, and the second outcomes were the levels of interleukin (IL)-6, C-reactive protein (CRP) and hemoglobin (Hb). The risk of bias was assessed by Cochrane Collaboration’ tool, and the quality of evidence was appraised with the Grading of Recommendation Assessment. Means and standard deviations were analyzed by random effects analysis. Stratified analysis was done and sensitivity analysis was performed when appropriate. Results: Totally, eight studies with 261 patients at CKD stage 3 to 5 with and without dialysis were included. We found a decrease of p-cresyl sulfate (PCS) of 3 studies with 125 subjects (P = 0.01, SMD -0.57, 95% CI, -0.99 to -0.14, I2 = 25%) and an increase of IL-6 in 3 studies with 134 subjects (P = 0.03, 95% CI, SMD 0.37, 0.03 to 0.72, I2 = 0%) in the probiotics groups. Analysis of serum creatinine (P = 0.47), blood urine nitrogen (P = 0.73), CRP (P = 0.55) and Hb (P = 0.49) yielded insignificant difference. Conclusion: Limited number of studies and small sample size are limitations of our study. Probiotics supplementation may reduce the levels of PCS and elevate the levels of IL-6 whereby protecting the intestinal epithelial barrier of patients with CKD.

Background It remains an urgent need for early recognition of disease severity, treatment option and outcome of Guillain-Barré syndrome (GBS). The chief complaint may be quickly obtained in clinic and is one of the candidates for early predictors. However, studies on the chief complaint are still lacking in GBS. The aim of the study is to describe the components of chief complaints of GBS patients, and to explore association between chief complaints and disease severity/treatment option/outcome of GBS, so as to aid the early prediction of the disease course and to assist the clinicians to prescribe an optimal early treatment. Methods A total of 523 GBS patients admitted to the First Hospital of Jilin University from 2003 to 2013 were enrolled for retrospective analysis. The data of chief complaints, clinical manifestations, and treatment options, etc. were collected. The clinical severity was evaluated by the Medical Research Council sum score and the Hughes Functional Grading Scale. The prognosis at 6 month after discharge was described by modified Erasmus GBS outcome score. The clinic GBS severity evaluation scale (CGSES), a newly established model in our study, was used to explore the role of chief complaints to predict intravenous immunoglobulin (IVIg). Results The major components of the chief complaints of GBS patients were weakness, numbness, pain, cranial nerve involvement, dyspnea, ataxia and autonomic dysfunction. Chief complaint of weakness was a predictor of severe disease course and poor short-term outcome, while chief complaint of numbness and cranial nerve involvement were promising predictors. Cranial nerve involvement was the predictor of ventilator dependence. The percentages of 366 GBS patients, who need IVIg treatment at nadir with CGSES ranging from 1 to 4, were 50.00, 67.34, 80.61, and 90.67%, respectively. Conclusions Chief complaints are clinic predictors of disease severity, ventilator dependence and short-term outcome. IVIg treatment during hospitalisation could be predicted in clinic using CGSES score.

// Ying Wang 1 , Wenjuan Lang 1 , Yaqian Zhang 1 , Xiaoyi Ma 2 , Chunkui Zhou 1 and Hong-Liang Zhang 1,3 1 Department of Neurology, The First Hospital of Jilin University, Changchun, China 2 Department of Neurology, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China 3 Department of Life Sciences, The National Natural Science Foundation of China, Beijing, China Correspondence to: Ying Wang, email: // Chunkui Zhou, email: // Hong-Liang Zhang, email: // Keywords : Guillain-Barre syndrome, long-term prognosis, predictors, self-limitation, intravenous immunoglobulin Received : July 12, 2017 Accepted : August 17, 2017 Published : September 01, 2017 Abstract Background: The long-term follow-up system for Guillain-Barre syndrome (GBS) is not well established worldwide. In our study, the preliminary data of the long-term prognosis of GBS are collected to explore the prognosis of GBS and the effect of intravenous immunoglobulin (IVIg) treatment. Methods: The follow-up data of 186 patients with GBS admitted from 2003 to 2013 were collected in 2015 via phone interview. The GBS disability scale score was ranked by clinician to evaluate the long-term prognosis. The clinical data during the acute phase were also collected. Results: The mortality rates were 2.15%, 5.45% and 7.89% at discharge, 2-5 years and 6-10 years after disease, respectively. The GBS disability scale score improved dramatically from discharge to 2-12 years after the acute phase. The self-limitation, the spontaneous recovery of disease, occurred both at acute phase and 2-5 years after discharge. Comparisons between IVIg-treated patients and GBS patients who only received supportive care revealed no significant difference of long-term prognosis. Conclusion: The long-term prognosis of GBS appears not to be influenced by treatment options. The long-term improvement of IVIg treated-patients might be due to the self-limitation of GBS per se instead of the IVIg treatment.

Objective: To present our treatment experiences and the follow-up data of patients with paradoxical embolism (PDE). Methods: The clinical characteristics, management, and follow-up data of all included patients who were diagnosed with PDE at Fuwai Hospital from January 1994 to October 2015 were recorded. Results: Twelve patients were included; all had a pulmonary embolism, and 8 had deep venous thrombosis. The artery embolisms involved the cerebral artery (7 patients), renal artery (2 patients), mesentery artery (2 patients), popliteal artery (1 patient), descending aorta thrombus (1 patient), and thrombus-straddled patent foramen ovale (PFO) (1 patient). PFO was found in 3 cases. One patient underwent thrombectomy and PFO closure; Six patients received thrombolysis; and 3 patients were implanted with a vena cava filter. Long-term anticoagulation with warfarin was recommended for each patient. One patient died from ventricular fibrillation despite cardiopulmonary resuscitation. Eleven patients were discharged with improvements. No late mortality occurred in 8 patients with a complete follow-up of 10.6â17.7 years. One had a recurrent deep venous thrombosis. No patient had a recurrent pulmonary or arterial embolism. Two patients changed their treatment from warfarin to aspirin; others remained on warfarin. Only 1 case had an occasional gum bleeding. Conclusions: PDE treatment including thrombolysis, anticoagulation, and embolectomy should be individualized. We recommend long-term anticoagulation therapy to prevent the recurrence of PDE, especially to those with an intracardiac communication or persistent risk factors for re-thrombosis. Keywords: Paradoxical embolism, Pulmonary embolism, Deep venous thrombosis, Patent foramen ovale

Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague‑Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14‑20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3β‑hydroxysteroid dehydrogenase (3β‑HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side‑chain cleavage enzyme and steroid 17 alpha‑hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3β‑HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4‑hydroxynonenalwere dose‑dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin‑like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3β‑HSD may be associated with impairment of the steroidogenic capacity.

Background Rheumatoid arthritis is an autoimmune disease characterized by symmetrical small arthritis. Anti-cyclic citrullinated peptide antibodies and rheumatoid factor are commonly used to diagnose RA[1]. However, the early diagnosis of RA is sometimes difficult, due to the heterogeneity and negative anti-CCP antibody or RF in some patients. Therefore, it is urgent to find autoantibodies with high sensitivity and specificity as diagnostic markers for RA. Objectives To screen autoantibodies of RA with high sensitivity and specificity using human proteome microarrays[2]. Methods Firstly, a case-control method was used to analyze the serum antibodies of RA patients using human proteome microarray which composed of 20,000 proteins, and identified RA-related antibodies. Then, expanded the sample size and analyzed the expression of these candidates between RA patients and healthy controls. Results The serum of five RA patients and five healthy controls were selected to detect the RA-related autoantibodies by microarray, and 25 candidates were screened. Then the IgG and IgM RA-focused microarrays composed of the 25 proteins were screened with additional cohorts of 72 RA patients and 106 healthy controls. The results of IgG protein microarray showed: (1) Expression of these 25 autoantibodies in RA patients was significantly higher than those in healthy controls (P 0.05). (3) ROC analysis showed that the combination of anti-RBPJ, anti-SH3BGR and anti-PAFAH1B3 autoantibody can be highly RA-specific biomarkers, with 66.7% sensitivity and 74.2% specificity, and the area under the curve is 0.734; meanwhile the sensitivity and specificity of the anti-CCP antibody and RF-negative RA patients diagnosis were 77.8% and 65.6%, and the area under the curve was 0.720. The results of IgM protein microarray showed: (1) Only 10 out of the 25 candidates’ expression was significantly higher in RA patients than healthy controls (P Conclusion The combination of IgG-type antibodies anti-RBPJ, anti-SH3BGR and anti-PAFAH1B3, the IgM-type antibody anti-PAFAH1B3 as well, has high sensitivity and specificity for the diagnosis of RA; especially the IgG-type autoantibody combination has great value for the diagnosis of anti-CCP and RF-negative RA patients. References [1] Silveira IG, et al. Anti-CCP antibodies have more diagnostic impact than rheumatoid factor (RF) in a population tested for RF. Clinical Rheumatology, 2007. 26(11): p.1883-1889. [2] Song Q, et al. Novel Autoimmune Hepatitis-Specific Autoantigens Identified Using Protein Microarray Technology. Journal of Proteome Research, 2010. 9(1): p.30-39. Acknowledgement This work was supported by grants from the National Natural Science Foundation of China (81771774) and the Anhui Provincial Natural Science Foundation (1708085MH191) Disclosure of Interests None declared

Background Gout is an inflammatory arthritis associated with hyperuricemia which is caused by purine metabolism disorders. General uric acid lowering treatment sometimes causes the onset of gout, but the specific cause is not clear. Our group has found that adenine nucleoside triphosphate (ATP) plays an important role in the pathogenesis of gout. It synergizes with MSU to stimulate the secretion of IL-1β, leading to the onset of gout.[1,2] The xanthine oxidase inhibitors promote the production of ATP, while the drugs that promotes the excretion of uric acid does not affect ATP production. Therefore, we speculate that gout attacks induced by allopurinol and febuxostat are related to the role that ATP plays in the pathogenesis of gout. Objectives To compare the effects of drugs that inhibit uric acid production and promote uric acid excretion on gout. Methods A case-control study was used to compare the changes in serum uric acid concentration and observe whether the patients would suffer gouty arthritis within one month. The gout patients complied with the standard that the number of gout attacks did not exceed three times, as well as more than one time within the past six months, were selected. And patients with other chronic inflammatory and infectious diseases were excluded. Results A total of 148 patients with gout in the Department of Rheumatology and Immunology of Anhui Provincial Hospital were collected, all of whom were male. According to the patients taking uric acid-lowering drugs, they were divided into four groups: group A: control group (no uric acid-lowering treatment, n=35); group B: febuxostat group (40 mg Qd, n=66); group C: allopurinol group (0.1 g Bid, n=11); group D: benzbromarone group (50mg Qd, n=36). The statistical results are as follows: (1) The levels of serum uric acid in group B, C and D were significantly decreased after uric acid-lowering treatment compared with those before treatment (B: 389.6±88.9 vs 547.5±93.0, C:363.3±28.6 vs 504.0±38.3, D: 376.2±108.5 vs 557.3±101.8) within one month, and there was no significant difference in the level of uric acid before uric acid-lowering treatment among the three groups. (2). Comparison of gouty arthritis recurrence rates: The recurrence rate of gout patients in group B was 33.3%, and was 18.2% in group C, which was significantly higher than that in group D (11.1%), the difference was statistically significant (P 0.05); the recurrence rate of gout patients treated by drugs that inhibited uric acid production (B+C group) was 31.2%, which was significantly higher than patients treated by drugs that promoted uric acid excretion (D group) 11.1%, the difference was statistically significant (P Conclusion Under the same uric acid-lowering intensity, the drugs that inhibit uric acid production can induce gout attacks during the process of uric acid lowering, while the drugs that promote uric acid excretion has less effect on the recurrence of gouty arthritis. References [1] Tao JH, et al. P2X7R: A potential key regulator of acute gouty arthritis. Semin Arthritis Rheum. 2013; 43(3): 376-380. [2] Tao JH, et al. Single nucleotide polymorphisms associated with P2X7R function regulate the onset of gouty arthritis. PLoS One. 2017Aug10;12(8):e0181685. Acknowledgement This work was supported by grants from the National Natural Science Foundation of China (81771774) and the Anhui Provincial Natural Science Foundation (1708085MH191) Disclosure of Interests None declared

Background: Gout is an inflammatory disease associated with hyperuricemia and characterized by recurrent arthritis. In previous study, MSU which generated by hyperuricemia was recognized by the toll-like receptor and NOD receptor of the intrinsic immune system, then activated the NALP3 inflammasome to induce the secretion of IL-1beta, causing gout. However, this mechanism cannot explain why most patients with hyperuricemia do not have gout attacks in clinical practice, suggesting that there may be other pathogenic signals in the flare of gout. Our team previously found that P2X7R might play a key regulatory role in the pathogenesis of gout [1].What’s more, single nucleotide polymorphisms associated with P2X7R function regulate the onset of gouty arthritis[2], suggesting that ATP, as the ligand of P2X7R, may be a second key signal in addition to MSU to stimulate gout attack. Objectives: To understand whether ATP act as a key factor in gout development besides MSU. Methods: The rat hyperuricemia model was prepared by intraperitoneal injection of the uratase inhibitor oxazinic acid. Followed by ATP injection into the tail vein to observe the incidence of arthritis and compared with the Coderre’s method-established gouty arthritis [3]. Results: Forty hyperuricemia rats were prepared and 0.5ml ATP (10mM) solution was injected into the tail vein of the rat respectively, about 95% (38 rats) developed spontaneous arthritis. This type of spontaneous arthritis is very different from the Coderre’s method in the following aspects: (1) The onset time of spontaneous arthritis is faster. The time of joint swelling in spontaneous arthritis peaked at 6.0±2.0 hours after ATP injection, while it took 2 to 3 days for arthritis caused by local injection of MSU to reach its peak. (2) The affected joints were different: The Coderre’s method joints swelling only at the MSU injection site. Spontaneous arthritis can involve multiple joints, in which 71% have one joint affected, 21% have two joints affected and 8% with three or more than three joints affected by redness and swelling. (3) Distinct histopathologic characteristic: In Coderre’s method, lymphocytes caused by local injection account for about 60%, with fewer neutrophils; In spontaneous arthritis, neutrophils account for more than 90% and lymphocytes are less. (4) Different sources of MSU: there is local MSU in spontaneous arthritis, which is associated with hyperuricemia; the local presence of MSU in Coderre’s arthritis was artificially injected. Conclusion: The spontaneous arthritis due to the synergistic effect of ATP and MSU is consistent with the characteristics of human gout arthritis, suggesting that ATP is the key second signal besides MSU to stimulate gout attack. References [1] Tao JH, Zhang Y, Li XP. P2X7R: A potential key regulator of acute gouty arthritis. Semin Arthritis Rheum. 2013; 43(3): 376-380. [2] Tao JH, Cheng M, Tang JP, et al. Single nucleotide polymorphisms associated with P2X7R function regulate the onset of gouty arthritis. PLoS One. 2017Aug10;12(8):e0181685. [3] CoderreTJ, Wall PD.Ankle joint urate arthritis (AJUA) in rats: An alternative animal model of arthritis to that produced by Freund’s adjuvant. Pain. 1987; 28(3):379-93. Acknowledgement: This work was supported by grants from the National Natural Science Foundation of China (81771774) and the Anhui Provincial Natural Science Foundation (1708085MH191) Disclosure of Interests: None declared

Background: Gout is an autoinflammatory disease characterized by hyperuricemia and recurrent arthritis. ATP and MSU synergistically activate NALP3 inflammasome to induce the secretion of IL-1β, leading to the onset of gouty arthritis, and P2X7R plays a key role in gout[1,2]. This mechanism above can explain the clinical phenomenon that some patients with hyperuricemia never suffer gouty arthritis, however, it cannot explain why the frequency of gout attacks increases as the course prolongs. Cholesterol or triglyceride can activate the innate immune and induce inflammatory response. It is speculated that Cholesterol and triglyceride levels can increase with the duration of gout, and they may reduce the threshold of gout attacks. Objectives: To demonstrate the effect of elevated cholesterol and triglyceride on the onset of gout. Methods: A cohort study was performed to observe the difference of arthritis episodes between the high cholesterol group and the normal, the high triglyceride group and the normal in gout patients. The frequency of gout attacks was compared using statistical methods of independent sample test and paired sample test between the two groups. Results: A cohort study was performed to observe the difference of arthritis episodes between the high cholesterol group and the normal, the high triglyceride group and the normal in gout patients. The frequency of gout attacks was compared using statistical methods of independent sample test and paired sample test between the two groups. RESULTS: A total of 68 patients with gout were observed. Among them, 21 were in normal cholesterol group, 13 in elevated group, 21 in normal triglyceride group and 13 in elevated group. The results of the independent sample test between the two groups are as follows: (1) The frequency of gout attacks between the normal cholesterol group and the elevated group is statistically significant within three months, six months and one year (0.81±0.60 vs 1.77±0.83, Z=-3.200, P=0.001; 1.14±0.73 vs 3.15±2.15, Z=-3.430, P=0.001; 1.43±0.81 vs 4.77±3.44, Z=-3.199, P=0.001). (2) The frequency of gout attacks between the normal triglyceride group and the elevated group is statistically significant within three months, six months and one year (0.81±0.60 vs 1.54±0.97, Z=-2.359, P=0.018; 1.14±0.73 vs 2.38±1.66, Z=-2.417, P=0.016; 1.43±0.81 vs 3.54±2.50, Z=-3.005, P=0.003). The results of the paired sample test between the two groups are as follows: (1) 6 pairs of normal cholesterol group and elevated group were screened according to age, course and uric acid level. There is significant difference in the frequency of gout attacks between the two groups within six months and one year (1.17±0.75 vs 2.83±2.23, Z=-2.060, P=0.039; 1.33±0.82 vs 4.17±3.43, Z=-2.032, P=0.042). (2) 11 pairs of normal triglyceride group and elevated group were screened as above. There is significant difference in the frequency of gout attacks between the two groups within one year (1.45±0.82 vs 3.45±2.58; Z=-2.328, P=0.020). Conclusion: Cholesterol and triglyceride levels can affect the frequency of gout attacks. The phenomenon mentioned in background can be explained by the increase of cholesterol and triglyceride levels as the course prolongs. Acknowledgement: This work was supported by grants from the National Natural Science Foundation of China (81771774) and the Anhui Provincial Natural Science Foundation (1708085MH191) References [1] Tao JH, et al. P2X7R: A potential key regulator of acute gouty arthritis. Semin Arthritis Rheum. 2013; 43(3): 376-380. [2] Tao JH, et al. Single nucleotide polymorphisms associated with P2X7R function regulate the onset of gouty arthritis. PLoS One. 2017Aug10;12(8):e0181685. Disclosure of Interests: None declared

Microglia are resident macrophage-like immune cells in the central nervous system (CNS) and play a vital role in both physiological and pathological conditions, including restoring the integrity of the CNS and promoting the progression of neurodegenerative disorders. Upon stimulation, microglia typically convert from a surveillant to an activated phenotype. The major function of microglia is to maintain homeostasis and normal function of the CNS, both during development and in response to CNS injury. Microglia regulate multiple aspects of inflammation, such as repair, cytotoxicity, regeneration, and immunosuppression due to their different kind of activation states or phenotypes. Although microglia are involved in almost all neurodegenerative disorders, the mechanisms for microglial activation and their potential contributions to neuronal degeneration remain a matter of intense debate. In inflammatory process of the CNS, polarized M1 microglia can produce proinflammatory cytokines, neurotoxic molecules, which contribute to dysfunction of neural network and promoting inflammation reaction, whereas polarized M2 microglia secrete antiinflammatory mediators and neurotrophic factors that are involved in restoring homeostasis. Modulation of microglial activation for therapeutic purposes might be realized via suppressing the deleterious effects of these cells, while simultaneously retaining their protective functions. Here, we summarize the functions of microglia and discuss dual role of microglia in neurodegenerative diseases as well as multiple sclerosis.

Background In the present study, we investigated the immuno-regulatory and therapeutic effects of Bowman–Birk inhibitor concentrate (BBIC) on experimental autoimmune neuritis (EAN), an animal model of Guillain–Barre syndrome (GBS) in human. Methods EAN in Lewis rats induced by inoculation with peripheral nerve myelin P0 protein peptide 180-199 (P0 peptide) was treated with BBIC at two different therapeutic regimens. Results Our data indicated that the administration of BBIC daily orally effectively inhibited and ameliorated the clinical and pathological signs of EAN. The suppression of EAN was associated with an insufficiency of autoreactive T cells, as reflected by inhibited P0 peptide-specific mononuclear cell proliferation and decreased in CD4 and CD8 T cells infiltrating into the peripheral nervous system (PNS). BBIC might mediate its therapeutic effects by shifting macrophages from M1 to M2 subtype as evidenced by increasing Arg-1, CD206 and IL-10 and inhibiting IFN-γ, TNF-α, IL-12, iNOS and CD40 expressions on macrophages as well as enhancing anti-inflammatory cytokines IL-4 and IL-10 and decreasing inflammatory cytokines, IFN-γ, TNF-α and IL-17 in the PNS. Conclusion Our results suggest that BBIC may have therapeutic potential in human GBS and other autoimmune diseases in the future.

Astrocytes, which are five-fold more numerous than neurons in the central nervous system (CNS), are traditionally viewed to provide simple structural and nutritional supports for neurons and to participate in the composition of the blood brain barrier (BBB). In recent years, the active roles of astrocytes in regulating cerebral blood flow (CBF) and in maintaining the homeostasis of the tripartite synapse have attracted increasing attention. More importantly, astrocytes have been associated with the pathogenesis of Alzheimer’s disease (AD), a major cause of dementia in the elderly. Although microglia-induced inflammation is considered important in the development and progression of AD, inflammation attributable to astrogliosis may also play crucial roles. A1 reactive astrocytes induced by inflammatory stimuli might be harmful by up-regulating several classical complement cascade genes thereby leading to chronic inflammation, while A2 induced by ischemia might be protective by up-regulating several neurotrophic factors. Here we provide a concise review of the emerging roles of astrocytes in the homeostasis maintenance of the neuro-vascular unit (NVU) and the tripartite synapse with emphasis on reactive astrogliosis in the context of AD, so as to pave the way for further research in this area, and to search for potential therapeutic targets of AD.

Severe pediatric traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Hypoperfusion of injured brain tissues after TBI is also associated with unfavorable outcomes. Therapeutic hypothermia is an investigational treatment strategy for use in patients with severe TBI that has shown differential effects on various cerebrospinal fluid (CSF) mediators in pediatric patients. Endothelin-1 (ET-1) is a powerful vasoconstrictor that exerts its effects on the cerebrovascular endothelium for sustained periods after TBI. The purpose of this study was to determine if CSF concentrations of ET-1 are increased after severe TBI in children, and if they are associated with demographics and outcomes that are affected by therapeutic hypothermia. This was an ancillary study to a prospective, randomized-controlled trial of early hypothermia in a tertiary care pediatric intensive care unit. Children (n = 34, age 3 months–15 years) suffering from severe TBI were randomized to hypothermia (n = 19) and normothermia (n = 15) as part of the efficacy study. Children undergoing diagnostic lumbar puncture (n = 11) to rule out infection were used as controls. Patients received either mild to moderate hypothermia (32–33°C) or normothermia as part of their treatment protocol. CSF was serially collected during the first 5 days after TBI. ET-1 concentrations were quantitated in patient and control CSF samples by a validated ELISA in duplicate with a limit of quantification of 0.195 pg/mL. CSF ET-1 concentrations were increased by two- to threefold in children after TBI compared to controls, and the increase was sustained for up to 5 days post-TBI. This relationship was not affected by hypothermia, and there were no differences in ET-1 response between children with inflicted and accidental TBI. Group-based trajectory analysis revealed two distinct groups with similar ET-1 levels over time. Univariate analysis showed a significant association between ET-1 levels and Glasgow Outcome Scale (GOS) scores, for which higher ET-1 levels over time were associated with unfavorable outcomes. ET-1 is increased in children with severe TBI and is associated with unfavorable outcomes. This increase in ET-1 may mediate the hypoperfusion or cerebrovascular dysfunction accompanying severe TBI in children. Importantly, hypothermia does not affect the brain's ET-1 response as measured in the CSF.

Background We describe a case of Guillain-Barre syndrome (GBS) associated with hemorrhagic fever with renal syndrome. To our knowledge, only five cases of GBS associated with Hantavirus infection have been reported so far. Case presentations A 62-year-old man presented intermittent fever, chill and oliguria. According to remarkable leukocytosis, atypical lymphocytes, thrombocytopenia and former dwelling in hemorrhagic fever-endemic area, he was suspected as hemorrhagic fever with renal syndromeand certified with positive Hantavirus IgG. Later, the patient had symmetrical flaccid paralysis of all extremities. Electromyography showed peripheral nerve injury (mainly in axon). The patient was diagnosed as having acute motor sensory axonal neuropathy (AMSAN). After immunoglobulin infusion, patient showed progressive recovery and was transferred 3 weeks after his first admission to a rehabilitation center. Conclusions Our case was the 6th reported case of GBS associated with hemorrhagic fever with renal syndrome. Moreover, we for the first time classified the subtype of GBS (AMSAN) based on the electrophysiology characteristics. GBS should be suspected in patients who are already diagnosed as hemorrhagic fever with renal syndrome when delayed symmetrical limb paralysis occurs. Until recent now, GBS was only reported in hemorrhagic fever patients in Europe and Asia, which termed as hemorrhagic fever with renal syndrome.

The aim of this study was to determine the associations between serum folate level and the clinical course and severity of Guillain-Barré syndrome (GBS). We retrospectively enrolled 112 pairs of GBS patients and age- and sex-matched healthy controls with measured serum folate levels. On admission, 21 (18.9%) GBS patients had folate deficiency, of which only two were female patients. Patients with normal folate levels had a shorter disease progression than those with folate deficiency (median progression duration: 6 versus 13 days, p < 0.001). Serum folate levels on admission were correlated with progression duration and Medical Research Council (MRC) sum score in the upper limbs at nadir (r = -0.261, p = 0.005; r = -0.208, p = 0.03) but not with the duration of hospital stay or GBS disability score (p > 0.05). Logistic regression analysis revealed that normal folate levels on admission were an independent predictor of faster GBS progression, along with younger age, intact deep sensation, and a lower MRC sum score on admission. These results show that serum folate levels are correlated with the progression duration and severity of GBS. Further studies are required to confirm the potential of folate level as a biomarker for GBS prognosis.

Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative disorder leading to deaf-blindness. USH is clinically subdivided into three subclasses, and 10 genes have been identified thus far. Clinical and genetic heterogeneities in USH make a precise diagnosis difficult. A dominant‑like USH family in successive generations was identified, and the present study aimed to determine the genetic predisposition of this family. Whole‑exome sequencing was performed in two affected patients and an unaffected relative. Systematic data were analyzed by bioinformatic analysis to remove the candidate mutations via step‑wise filtering. Direct Sanger sequencing and co‑segregation analysis were performed in the pedigree. One novel and two known mutations in the USH2A gene were identified, and were further confirmed by direct sequencing and co‑segregation analysis. The affected mother carried compound mutations in the USH2A gene, while the unaffected father carried a heterozygous mutation. The present study demonstrates that whole‑exome sequencing is a robust approach for the molecular diagnosis of disorders with high levels of genetic heterogeneity.

Sperm-specific sodium-hydrogen exchanger (sNHE) is essential to maintain sperm normal function in mice; however, its role in human sperm has not been clarified to date. The aim of this study is to investigate the expression pattern of sNHE in human spermatozoa and its relationship with sperm functional parameters. Semen samples from 68 asthenozoospermic and 61 normozoospermic men were analyzed for sperm concentration, motility, and acrosome reaction, and high motile spermatozoa were collected by swim-up method. The expression of sNHE in spermatozoa was detected by Western blot and immunofluorescence staining. The relationship between sNHE expression and sperm parameters was assessed. We identified sNHE is mainly localized to the principal piece of the human sperm tail. The expression of sNHE was positively correlated with sperm concentration, total number, and progressive motility. Moreover, sNHE expression was upregulated in swim-up sperm and associated with most of sperm motility parameters including straight line velocity and curvilinear velocity. Our results also showed that sNHE expression is decreased in sperm from patients with asthenozoospermia compared with that from normal controls. However, no correlation was found between sNHE expression and acrosome reaction in spermatozoa. The expression pattern of sNHE suggested that this protein may be involved in the regulation of sperm motility, and aberration of its expression in sperm may contribute to the pathogenesis of asthenozoospermia.

This article contains the clinical characteristics of the paradoxical embolized patients and the following up results. Data included are related to the article “Paradoxical embolism: Experiences from a single center” (Zhang Hong-liang, Liu Zhi-hong, Luo Qin, Wang Yong, Zhao Zhi-hui, Xiong Chang-ming, in press) [1]. The data are obtained from the hospital records and telephone interview.

Male infertility is considered a common health problem, and non-obstructive azoospermia with unclear pathogenesis is one of the most challenging tasks for clinicians. The objective of this study was to investigate the differential serum metabolic pattern in non-obstructive azoospermic men and to determine potential biomarkers related to spermatogenic dysfunction. Serum samples from patients with non-obstructive azoospermia (n = 22) and healthy controls (n = 31) were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Serum metabolomic profiling could differentiate non-obstructive azoospermic patients from healthy control subjects. A total of 24 metabolites were screened and identified as potential markers, many of which are involved in energy production, oxidative stress and cell apoptosis in spermatogenesis. Moreover, the results showed that various metabolic pathways, including d-glutamine and d-glutamate metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, the citrate cycle and alanine, aspartate and glutamate metabolism, were disrupted in patients with non-obstructive azoospermia. Our results indicated that the serum metabolic disorders may contribute to the etiology of non-obstructive azoospermia. This study suggested that serum metabolomics could identify unique metabolic patterns of non-obstructive azoospermia and provide novel insights into the pathogenesis underlying male infertility.

Rationale: Neuromyelitis optica spectrum disorders (NMOSD) is considered as an immune-mediated disorder in the central nervous system (CNS). Numerous autoimmune diseases are frequently complicated with NMOSD and distinct clinical characteristics are noted in NMOSD patients with other autoimmune diseases. However, to our best knowledge, co-occurrence of NMOSD and thrombopenic purpura is rarely identified. Patient concerns: We presented a rare case of a 72-year-old female with 6-year history of thrombopenic purpura, and 1-month history of blurred vision as well as chest zonethesia. Anti-aquaporin-4 (AQP4) antibodies was positive in the serum of the patient. Diagnoses: With the addition of laboratory findings, iconography findings and physical examination results, the diagnosis of NMOSD was established according to the most recent diagnostic criteria. Interventions and outcomes: With the treatment of intravenous immunoglobulin (IVIg), the patient felt better at discharge without changing of expanded disability status scale (EDSS) score. Lessons: The case indicates that NMOSD could co-occur with thrombopenic purpura. The disturbance of immune system balance may explain this overlap. Further studies are warranted to reveal the mechanism and to explore whether patients with NMOSD with and without thrombopenic purpura have distinct clinical feature, drug responsiveness or prognosis.

Guillain-Barre syndrome (GBS) is generally considered to be a post-infectious autoimmune disorder with incompletely clear pathogenesis. However, both infectious and noninfectious factors have been reported to trigger the onset of GBS. We report herein a 31-year-old man who developed acute motor axonal neuropathy after closed head injury hemorrhage in the right frontal lobe and subarachnoid hemorrhage. Whereas he was exempted from any neurological function deficits, intravenous ganglioside was prescribed for treating the head injury. Seven days later, however, tetraplegia and bilateral facial paralysis as well as respiratory failure requiring mechanical ventilation developed. Albumino-cytologic dissociation in the cerebrospinal fluid and electrophysiological findings indicative of axonal impairment supported a diagnosis of acute motor axonal neuropathy.

Guillain-Barré syndrome (GBS) is an immune-mediated acute inflammatory disorder of the PNS in humans characterized by inflammatory infiltration and damage to myelin and axon. Experimental autoimmune neuritis (EAN) is a useful animal model for studying the pathogenesis and treatment of GBS. Immunocompetent cells together with cytokines produced by various cells contribute to the inflammatory process of GBS and EAN by acting as mediators or effectors.Both GBS and EAN have long been attributed to T helper (Th) 1 cell-mediated autoimmune disorders. IFN-γ acts as a central mediator of Th1-mediated autoimmune disorders by deflecting the immune response toward a Th1 phenotype by inducing the differentiation of T cells to a Th1 phenotype and inhibiting the development of Th2 cells in autoimmune disorders such as GBS. In this review, we present an overview of current knowledge on the inflammatory and immunoregulatory role of IFN-γ in GBS and EAN, which is important for evaluating whether IFN-γ can become a potential therapeutic target in GBS.Analysis of immunopathogenesis of GBS and EAN revealed the significance of IFN-γ in both diseases, even though the complex mechanism of the delicate modulation of the cytokine is still under debate. More work needs to be done to rule out its potential in immunoregulatory function and pave the way for new therapeutic strategies for GBS.