Disturbance of serum lipid metabolites and potential biomarkers in the Bleomycin model of pulmonary fibrosis in young mice.

BACKGROUND: Altered metabolic pathways have recently been considered as potential drivers of idiopathic pulmonary fibrosis (IPF) for the study of drug therapeutic targets. However, our understanding of the metabolite profile during IPF formation is lacking. METHODS: To comprehensively characterize the metabolic disorders of IPF, a mouse IPF model was constructed by intratracheal injection of bleomycin into C57BL/6J male mice, and lung tissues from IPF mice at 7 days, 14 days, and controls were analyzed by pathology, immunohistochemistry, and Western Blots. Meanwhile, serum metabolite detections were conducted in IPF mice using LC-ESI-MS/MS, KEGG metabolic pathway analysis was applied to the differential metabolites, and biomarkers were screened using machine learning algorithms. RESULTS: We analyzed the levels of 1465 metabolites and found that more than one-third of the metabolites were altered during IPF formation. There were 504 and 565 metabolites that differed between M7 and M14 and controls, respectively, while 201 differential metabolites were found between M7 and M14. In IPF mouse sera, about 80% of differential metabolite expression was downregulated. Lipids accounted for more than 80% of the differential metabolite species with down-regulated expression. The KEGG pathway enrichment analysis of differential metabolites was mainly enriched to pathways such as the metabolism of glycerolipids and glycerophospholipids. Eight metabolites were screened by a machine learning random forest model, and receiver operating characteristic curves (ROC) assessed them as ideal diagnostic tools. CONCLUSIONS: In conclusion, we have identified disturbances in serum lipid metabolism associated with the formation of pulmonary fibrosis, contributing to the understanding of the pathogenesis of pulmonary fibrosis.

Predictors and mechanisms of epilepsy occurrence in cerebral gliomas: What to look for in clinicopathology.

Gliomas, especially low-grade gliomas, are highly epileptogenic brain tumors. Histopathological information is valuable in evaluating the diagnosis and/or biologic behavior of various gliomas. Here we explored the clinical data and histopathological predictors of the occurrence of epilepsy in patients with gliomas. A retrospective study examined 310 consecutive patients who had undergone surgical treatment for gliomas in our institution from January 2013 to January 2015. Clinical data and pathological examination results were analyzed. Literatures regarding the predictors and etiology of glioma associated epileptic seizures in the period of 1995-2015 were also reviewed. A total of 234 (75.5%) astrocytic tumors and 76 (24.5%) oligodendrial tumors were included. At diagnosis, 33.6% of patients had epileptic seizures. Multivariate analysis revealed cortex involvement (OR=7.991, 95%CI=1.599-39.926), lower World Health Organization grade (OR=3.584, 95%CI=1.032-12.346) and topoisomerase II (TopoII) positivity (OR=0.943, 95%CI=0.903-0.982) were strong predictors for preoperative epileptic seizures. Gender, disease course, tumor classification, location or volume did not significantly affect epileptic seizure occurrence. Forty-three publications involved glioma-associated epilepsy were found in PubMed online database and key data were extracted and summarized. The present studies on glioma-related epilepsy are relatively limited and inconsistent. Low-grade gliomas, cortex involvement and TopoII positivity were independent predictors of a history of epileptic seizures at diagnosis. Further studies to examine the underlying mechanism of topoisomerase II as well as other molecules in epilepsy occurrence in brain gliomas are needed in the future.

Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis: A systematic review of reported cases.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a recently recognized autoimmune disorder which is responsive to immunotherapy. However, the outcomes of different immunotherapies have not been defined and there have been few studies that carried out a comparison among them. To provide an overview of the clinical characteristics, treatments, and outcomes of anti-NMDAR encephalitis, we systematically reviewed the literature in the PubMed, Medline, Embase, Cochrane Library, BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang databases. Eighty-three studies with a total of 432 patients were included. The median age was 22years. Two hundred ninety-three (68%) patients were female, 87 (21%) of 412 patients had a tumor, including 68 (78%) patients with ovarian teratoma. Pediatric patients had a higher ratio of seizures to psychiatric symptoms as the initial manifestation (p=0.0012), a lower proportion with a tumor (p<0.0001) and CSF pleocytosis (p=0.0163), and a better outcome (p=0.0064) than adults. Patients who died had a higher proportion of CSF pleocytosis than the patients who survived (p=0.0021). There were no significant differences among three first-line immunotherapy used alone (p=0.9172) or among combinations of every two of them (p=0.3059). With regard to the use of corticosteroid and IVIG, there were no significant differences between the outcomes of early combined treatment and sequential treatment (p=0.7277), or between using corticosteroid first and IVIG first (p=0.5422). Our findings suggest that the clinical characteristics and outcomes for pediatric patients were different from adult patients, and no significant differences were found among different immunotherapies.

Assessment of Utilization and Cost-Effectiveness of Telemedicine Program in Western Regions of China: A 12-Year Study of 249 Hospitals Across 112 Cities.

BACKGROUND: The imbalance in healthcare between urban and rural areas is still a problem in China. In recent decades, China has aimed to develop telemedicine. We assessed the implementation, utilization, and cost-effectiveness of a large telemedicine program across western China. MATERIALS AND METHODS: In 2002-2013, a government-sponsored major telemedicine program was established by West China Hospital of Sichuan University (hub), covering 249 spoke hospitals in 112 cities throughout western China and in 40 medical expertise areas. We analyzed the cross-sectional data from 11,987 consultations conducted at West China Hospital using the telemedicine network over a 12-year period. The types of diseases as well as the diagnosis and treatment changes were assessed. We also performed a cost-savings analysis and a one-way sensitivity analysis. RESULTS: Of the 11,987 teleconsultations, we noted that neoplasms (19.4%), injuries (13.9%), and circulatory diseases (10.3%) were the three most common diagnoses. Teleconsultations resulted in a change of diagnosis in 4,772 (39.8%) patients, and 3,707 (77.7%) of them underwent major diagnosis changes. Moreover, it led to a change of treatment in 6,591 (55.0%) patients, including 3,677 (55.8%) changes not linked to diagnosis changes. The telemedicine network resulted in an estimated net saving of $2,364,525 (if the patients traveled to the hub) or $3,759,014 (if the specialists traveled to the spoke hospitals). CONCLUSIONS: The introduction of telemedicine in China, linking highly specialized major hospitals (hub) with hundreds of small rural hospitals (spoke), can greatly improve the quality, efficiency, and cost-effectiveness of healthcare delivery and utilization. This new Internet-based healthcare model should be utilized more widely in developing countries.

Association between RAD51 gene polymorphism (-135G/C) and susceptibility of myelodysplastic syndrome and acute leukemia: evidence based on a meta-analysis.

Study results on the association between RAD51 gene -135G/C polymorphism and risk of myelodysplastic syndrome (MDS) or acute leukemia are inconsistent. A meta-analysis was conducted to identify the association. A systematic search was performed in PubMed, Embase, CNKI, VIP, Wanfang databases to collect all relevant studies until January 2013. Meta-analysis was carried out using fixed/random model by Review Manager 5.1 and STATA10.0. A total of 10 eligible studies with 2,656 patients and 3,725 controls were included in meta-analysis. Significant association was detected between -135G/C polymorphism and increased MDS risk (CC + GC vs. GG: OR = 1.46, 95% CI = 1.11-1.92; CC vs. GC + GG: OR = 2.45, 95% CI = 1.23-4.89), while no association was observed for acute leukemia. Subgroup analysis by subtypes of acute leukemia and ethnicity showed no significant results either. Our meta-analysis indicated that the -135G/C polymorphism might be associated with increased susceptibility of MDS. However, lack of evidence supported association of this polymorphism with acute leukemia. Additional well-designed studies with larger samples are required to verify our results.

NBS1 Glu185Gln polymorphism and cancer risk: update on current evidence.

A number of studies have investigated the association between NBS1 Glu185Gln (rs1805794, E185Q) polymorphism and cancer risk, but the results remained controversial. Previous meta-analysis found a borderline significant impact of this polymorphism on cancer risk; however, the result might be relatively unreliable due to absence of numerous newly published studies. Thus, we conducted an updated meta-analysis. A systematic search was performed in PubMed and Embase databases until April 9, 2013. The odds ratios were pooled by the fixed-effects/random-effects model in STATA 12.0 software. As a result, a total of 48 case-control studies with 17,159 cases and 22,002 controls were included. No significant association was detected between the Glu185Gln polymorphism and overall cancer risk. As to subgroup analysis by cancer site, the results showed that this polymorphism could increase the risk for leukemia and nasopharyngeal cancer. Notably, the Glu185Gln polymorphism was found to be related to increased risk for urinary system cancer, but decreased risk for digestive system cancer. No significant associations were obtained for other subgroup analyses such as ethnicity, sample size and smoking status. In conclusion, current evidence did not suggest that the NBS1 Glu185Gln polymorphism was associated with overall cancer risk, but this polymorphism might contribute to the risk for some specific cancer sites due to potential different mechanisms. More well-designed studies are imperative to identify the exact function of this polymorphism in carcinogenesis.

Psychiatric Symptoms of Patients With Anti-NMDA Receptor Encephalitis.

Objective: We conducted this study to analyze the clinical characteristics of the psychiatric symptoms of patients with anti-NMDAR encephalitis. Methods: A retrospective study of anti-NMDAR encephalitis in China was performed. The clinical characteristics of the psychiatric symptoms, the relationship between the antibodies titers and clinical characteristics of patients with anti-NMDAR encephalitis were determined. Results: A total of 108 patients with a definitive diagnosis of anti-NMDAR encephalitis were included in this study. 103 patients (95%) developed one or several psychiatric symptoms. The comparison of the high titer group and the low titer group showed that more patients presented psychiatric symptoms as the initial symptom in the high titer group (P = 0.020), the prevalence of the symptoms such as depressive, catatonic, and central hypoventilation were also higher in the high titer group than the low titer group (P = 0.033, 0.031 and 0.006, respectively). Meanwhile, more patients received a combination treatment of IVIg and corticosteroids in the high titer group than the low titer group and patients in high titer group were prescript with anti-psychiatric drugs more often than the patients in low titer group (P = 0.026 and 0.003, respectively). Conclusions: Psychiatric symptoms are the most common clinical characteristics of patients with anti-NMDAR encephalitis. Patients with higher antibodies titers more often presented with psychiatric symptoms as the initial symptom, and showed a more severe clinical feature. Screening for the anti-NMDAR antibodies is essentially important in patients who present psychiatric symptoms with or without other neurological symptoms.

Brain magnetic resonance-imaging findings of anti-N-methyl-D-aspartate receptor encephalitis: a cohort follow-up study in Chinese patients.

The aim of this report was to assess routine clinical brain magnetic resonance imaging (MRI) and its relation to clinical characteristics and disease prognosis. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients were consecutively recruited from West China Hospital between October 1, 2011 and April 1, 2016. Brain MRI findings of 106 patients were analysed, and outcomes were assessed at 4, 8, and 12 months after discharge from the hospital using the modified Rankin scale (mRS). An MRI of the brain was normal in 52/106 (49.1%) patients and abnormal or atypical in 54/106 (50.9%) patients. The initial MRI was abnormal with T2 or fluid-attenuated inversion recovery (FLAIR) hyper-intensity signals in 20/106 (18.9%) patients. There were no statistically significant differences between the MRI findings and clinical presentations (seizure, hypoventilation, loss of consciousness, and tumour) (P > 0.05). Patients with normal MRIs were younger than patients with abnormal MRIs (P < 0.05). The mean mRS score at the 4-month follow-up was significantly higher in patients with abnormal MRIs than in patients with normal MRIs (P < 0.05). Brain MRI abnormalities are typically mild or unrelated to clinical symptoms, which is a clinico-radiological paradox of this type of immune encephalitis. Abnormal MRIs did not affect prognosis evaluated by mRS.

Inhibition of P2X7 Receptor Ameliorates Nuclear Factor-Kappa B Mediated Neuroinflammation Induced by Status Epilepticus in Rat Hippocampus.

P2X7 receptor (P2X7R) has been reported participating in neuroinflammation in multiple neurological diseases. We explored the role of P2X7R in a rat status epilepticus (SE) model induced by coriaria lactone (CL) and its association with neuroinflammation. Thirty minutes after intracerebroventricular infusion with P2X7R antagonists Brilliant blue G (BBG), A-438079, A-740003, or agonists 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), SE was induced by intramuscular injection of CL in Sprague-Dawley rats. Seizures severity was recorded according to the Racine scale and Morris water maze test was performed. P2X7R expression was measured by western blotting. Immunohistochemical staining was performed to assess pro-inflammation cytokines expression, neuronal loss, and astrocyte activation. The results showed P2X7R level began to increase at 1 day, peaked at 2 days, and gradually decreased to baseline by 2 weeks in rat hippocampus after SE. P2X7R activation induced NF-κB phosphorylation, along with increased IL-1ß and IL-6 expression. Pretreatment with P2X7R antagonists ameliorated SE-induced neuroinflammation, neuronal damage, and astroglial and microglial activation to variable extent. In addition, these antagonists ameliorated seizure severity and improved cognitive function. These findings suggest P2X7R activation plays a critical role in epileptogenesis via regulation of neuroinflammation and blocking P2X7R may be a novel therapeutic strategy for epilepsy.

Putting the new ILAE classification of focal cortical dysplasia into practice in western China.

PURPOSE: To re-examine drug-resistant epilepsy cases using the revised 2011 ILAE classification of focal cortical dysplasia (FCD). METHODS: Patients with drug-resistant epilepsy who have undergone epilepsy surgery in West China Hospital between July 2012 and Jun 2014 were included. Clinical histories, pathological diagnoses, and surgical outcomes were reviewed. A questionnaire was developed to investigate the clinical practice of the new classification. A short-term training program on FCD was carried out to improve pathological diagnosis accuracy. RESULTS: 260 consecutive cases (177 male and 83 female) were included. Pathological diagnosis was changed in 70 cases (26.9%) after re-examination. The five most common pathological types were hippocampal sclerosis (19.2%, 50/260), brain tumors (17.7%, 46/260), vascular malformations (16.2%, 42/260), glial scars (11.2%, 29/260) and FCD (10.0%, 26/260). The most common subtype of isolated FCD was FCD IIb (53.8%, 14/26), followed by FCD IIa (42.3%, 11/26) and FCD Ib (3.8%, 1/26). In addition, forty-five cases were diagnosed as associated FCD type III (17.3%, 45/260). Half of patients with FCD achieved Engel class I at two-year follow-up. Questionnaire investigation suggested most participant pathologists lack sufficient knowledge on the new classification. The diagnostic sensitivity for different FCD subtypes was significantly improved by two to six folds after short-term training. CONCLUSIONS: FCD is an important etiology of drug-resistant epilepsy in western China. It is essential to provide continuing trainings to improve diagnostic precision of FCD in developing countries.

Suicidality is a common and serious feature of anti-N-methyl-D-aspartate receptor encephalitis.

We aimed to assess suicidality risk amongst people who had had anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. All people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and February 2017 were identified and their notes were retrospectively reviewed. Demographic and clinical characteristics and risk predictors for suicidality were summarized; those with suicidality were compared to those without. 17 of 133 people (13%) presented with suicidality symptoms: 7 (5%) with suicidal ideation; 8 (6%) who attempted suicide; and 2 (1.5%) who completed suicide. Median age was 27 (16-78) years, most were female [13 (76%)]. Compared with those with no suicidality, psychiatric symptoms as the initial symptoms were more frequent in those who reported suicidality (p = 0.039); insomnia, aggression, mania, depression and delusion were also more common (p < 0.05). The use of antidepressants (p < 0.001) and recurrence of encephalitis (p = 0.020) were higher in people with suicidality than in those without. Other characteristics were not significantly different in those who had suicidality and those who did not. Suicidality is a common and potentially lethal risk for people with anti-NMDAR encephalitis. Those presenting with psychiatric symptoms as the initial symptom and with insomnia, aggression, mania, depression and delusion should be carefully screened for suicidality. Closely monitoring people who have been treated with antidepressants is necessary.

Clinical features and prognosis of epilepsy in the elderly in western China.

PURPOSE: To investigate the characteristics and prognosis of epilepsy amongst older people hospitalized in southwestern China with newly diagnosed epilepsy. METHODS: We prospectively enrolled people older than 65 years who were admitted to a tertiary epilepsy center in West China between January 2008 and January 2013. Participants were divided into early-onset group (those who had a first seizure before age of 65) and late-onset group (those in whom the first seizure occurred after age of 65). Clinical data were collected and all participants were followed for two years. RESULTS: Of 340 people enrolled, focal seizure (84%) was the most frequent seizure type. Status epilepticus (64.4% vs. 46.7%, p=0.022) and structural epilepsy (59.3% vs. 40.0%, p=0.015) were more prevalent in late-onset group than early-onset group. Ischemic stroke was the leading putative cause (22.6%) in elderly epilepsies. Around 80% were given anti-epileptic drugs (AEDs) for treatment. Forty-two people did not complete the study, of whom 26 were lost to follow-up and 16 died for causes other than epilepsy. Of the 298 who completed the follow-up, 240 (80.5%) achieved significant seizure reduction. Logistic regression analysis indicated that late-onset epilepsies and AEDs treatment were associated with more favorable seizure outcome at two-year follow-up (OR=4.029 and 92.007, respectively). The number of AEDs intake exerted no significant impact on seizure outcome. CONCLUSIONS: In older people, late-onset epilepsies differed in several aspects from early-onset epilepsies. The overall effectiveness of AEDs treatment in older people was satisfactory.