Search

The present study was undertaken to decipher the role of HOXC10 gene in regulating the growth and metastasis of prostate cancer. The results revealed significant (p

Objectives JDM is a rare autoimmune inflammatory muscle disease with a pronounced IFN signature. Treatment for children with JDM has improved over the years with the use of steroids and immunosuppressive agents. However, there remains a subset of children who have refractory disease. Janus kinase and type I IFN signalling production are suspected to contribute to the pathogenesis of JDM. Our pilot study investigated the use of tofacitinib, a Janus kinase inhibitor, in refractory JDM cases to provide new therapeutic options for better treatment. Methods Refractory JDM was defined as patients who failed two or more steroid sparing agents or high-dose steroids. Tofacitinib was given to three refractory JDM patients with a dose of 5 mg twice per day for at least 6 months. Core set measures defined by Pediatric Rheumatology International Trials Organization were evaluated at month 0, 3 and 6 along with other systemic evaluations. A literature review was conducted to identify all the cases using Janus kinase inhibitors in JDM. Results All three subjects tolerated and responded well to tofacitinib with significant improvement in Child Myositis Assessment Scale, manual muscle testing-8, physician global disease activity and inflammatory indices without occurrence of severe adverse events. Conclusion This pilot study showed improvement of muscle strength, resolution of cutaneous lesions, increased daily quality of life and successful tapering of steroids when tofacitinib used in selected cases. Tofacitinib can be considered with caution when treating refractory JDM cases. Further randomized controlled trials are warranted to assess its efficacy in JDM.

Background Systemic juvenile idiopathic arthritis (sJIA) has many clinical features overlapping with familial Mediterranean fever (FMF), which is caused by mutations in MEFV gene. And FMF patients were easily misdiagnosed as sJIA in China. So we speculate that MEFV is critical genetic background for sJIA and influences patients’ severity. In this study, we aim to figure out whether MEFV mutations are risk factor for the occurrence of sJIA and to study the association of MEFV mutations with disease severity of sJIA patients. Methods The present study includes 57 sJIA children and 2573 healthy controls. Odd ratio with 95% confidence interval based on allelic frequency of MEFV mutations or variants was used to evaluate their contribution to sJIA susceptibility. Meta-analysis was then performed to reach comprehensive conclusion. All included sJIA patients were grouped by presence and number of MEFV mutations. Clinical data and indicators of disease severity were compared among different groups. Multiple linear regression method was used to find out whether the number of MEFV variants is associated with the severity of sJIA. Kaplan-Meier curves and log rank test were used to estimate the probability of the first relapse. Results The MEFV mutations of our subjects predominantly existed in exons 2 and 3. No significant difference was found in allelic frequency between sJIA children and healthy controls. Meta-analysis demonstrated that p.M694V/I was a risk factor for sJIA (pooled OR: 7.13, 95% CI: 3.01–16.89). The relative period of activity was significantly lower in the one mutation group than those with more than one mutation (p = 0.0194). However, no relevance was found in multiple linear regression models. Conclusions The mutation p.M694V/I in MEFV might be a risk factor for sJIA. SJIA patients carrying more than one heterozygous mutation in MEFV tend to be more severe than those containing only one, but studies in other cohort of patients need to be performed to validate it.

Background The aim of this study was to evaluate the clinical performance of the BD Kiestra InoqulA automated specimen processing system with commonly encountered clinical microbiology specimens. Materials and methods Four types of clinical specimens (sputum, urine, normally sterile body fluids, and feces) were inoculated onto relevant agar plates using a manual method and the BD Kiestra automated system. The number of isolated pathogen species, number of isolated single colonies and uniformity of plate streaking were calculated and compared between two methods. Results Significantly more isolated colonies were observed on plates inoculated by InoqulA for all specimen types and media with the exception of sputum specimens inoculated onto chocolate agar with vancomycin (P =0.076) and urine onto China blue agar (P =0.856). The quality of plate streaking was also better with InoqulA for all specimen types and media with the exception of urine specimens (P =1.000) and sterile body fluids (P =0.56) inoculated onto China blue agar. Conclusion This is the first evaluation study of InoqulA with 4 types of clinical specimens in China. It focused on the effect of streaking plates automatically with the magnetic bead. Inoculation of clinical specimens with the BD Kiestra InoqulA system is superior to the manual method for recovery of single colonies and the overall quality of semi-quantitative plate streaking.

ROSAH syndrome was recently identified as an autosomal dominant systemic disorder due to mutations in ALPK1. It was characterized by retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. We collected and summarized the clinical data of two patients with juvenile onset splenomegaly and oculopathy. Whole exome sequencing (WES) was adapted for genetic analysis. Mutations in ALPK1 were confirmed by Sanger sequencing. Besides juvenile oculopathy and splenomegaly, both patients had intermittent fever and anhidrosis. Patient 2 also experienced recurrent upper respiratory infections in her infancy and developed dental and nail problems in childhood. Elevated TNF-α was their prominent laboratory features. Both patients were found to have a previously reported mutation, c.710C>T, p. T237M (NM_001102406) in ALPK1. Anti-TNF treatment of adalimumab was applied to patient 1, after which her optic disc edema in the left eye continued and the visual acuity deteriorated further. Patient 1 underwent elective splenectomy due to concern for spontaneous rupture of the spleen. Up to date, 18 patients of ROSAH syndrome have been reported. The clinical manifestations were relatively homogeneous, prominently presenting with juvenile onset oculopathy and splenomegaly. As it mainly involves ocular fundus, severe oculopathy deeply affects the quality of life and prognosis of ROSAH patients. Now little has been known about its treatment. As a newly recognized inherited systemic disorder, ROSAH syndrome needs to be paid more attention to, especially for those with juvenile onset splenomegaly and oculopathy.

The nucleotide-binding oligomerization domain-like receptor protein 12 (NLRP12)-autoinflammatory disorder (NLRP12-AD) is a rare autoinflammatory disease characterized by recurrent fever, rash as well as musculoskeletal symptoms, which is rarely reported in Asian populations. Three cases of NLRP12-AD presented to our hospital were studied after parental consents were obtained. Clinical presentations were recorded on a standardized case report form. Mutations of NLRP12 were detected by primary immunodeficiency disease panels and further examined by Sanger sequencing. PubMed literature search for relevant studies of systemic autoinflammatory disorders, especially NLRP12-AD between January, 2000 and January, 2019 was carried and the clinical data were summarized. Comparisons were made between groups in terms of onset age and of ethnicity. All our patients presented with fever, rash and arthritis/arthralgia, and sensorineural as well as sensorineural deafness (1/3), uveitis (1/3), abdominal pain (1/3), and myalgia (1/3). Two novel mutation variations, p.W581X and p.L558R, are reported here. In addition, we also found that two patients inherited the mutated alleles from their healthy parents, and this may be evidence of haploinsufficiency. Although the genotypes are similar, the clinical manifestations between Chinese patients and Western patients vary thus highlighting the possible influence of ethnic and environmental factors. On the other hand, some genetic mutations may lead to specific phenotype, as we have found a high prevalence of sensorineural hearing loss among p.R284X patients.

Cognitive deficits and psychiatric disorders have been regarded as the most common clinical symptoms of methamphetamine (MA) users. Accumulating evidence has shown that liver disease may be involved in cognitive deficits and psychiatric disorders. This study examines whether cognitive deficits and psychiatric symptoms are associated with serum levels of liver biomarkers in MA users. Cognition was assessed by the Repeatable Battery for the Assessment of neuropsychological Status (RBANS). Psychiatric symptoms were assessed by the Symptom Checklist-90 (SCL-90). Liver function was assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, Apolipoprotein B (ApoB), triglyceride, total cholesterol, and glucose concentrations in 106 MA addicts and 76 controls. Compared to control subjects, MA users had greater severity of psychotic symptoms on the dimension of somatization, depression, anxiety, psychoticism, addiction, and global severity index in SCL-90, and lower scores of cognition, including the total RBANS score and all five subscales. The globulin levels were increased, while the albumin, albumin/globulin, and ApoB levels were decreased. ApoB levels were positively correlated with immediate memory, attention, and total RBANS score. Furthermore, stepwise multivariate regression analysis indicated that ApoB levels were associated with immediate memory, attention, and total RBANS score. The findings of this study suggest that MA addicts might experience cognitive deficits, psychiatric disorders, and liver damage. Serum ApoB levels may be involved in cognitive deficits; thus, improving liver function may help to treat cognitive deficits and psychiatric disorders in MA addicts.

BACKGROUND Systemic-onset juvenile idiopathic arthritis (SoJIA) is one of most serious subtypes of juvenile idiopathic arthritis. Although the pathogenesis of SoJIA remains unclear, several studies have suggested a correlation between gut dysbiosis and JIA. Further understanding of the intestinal microbiome may help to establish alternative ways to treat, or even prevent, the disease. AIM To explore alterations in fecal microbiota profiles in SoJIA patients and to evaluate the correlations between microbiota and clinical parameters. METHODS We conducted an observational single-center study at the Pediatric Department of Peking Union Medical College Hospital. Children who were diagnosed with SoJIA at our institution and followed for a minimum period of six months after diagnosis were recruited for the study. Healthy children were recruited as a control group (HS group) during the same period. Clinical data and stool samples were collected from SoJIA patients when they visited the hospital. RESULTS The SoJIA group included 17 active and 15 inactive consecutively recruited children; the control group consisted of 32 children. Firmicutes and Bacteroidetes were the two most abundant phyla among the total sample of SoJIA children and controls. There was a significant difference among the three groups in observed species, which was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA group and then HS group (Active-SoJIA vs HS: P = 0.000; and Inactive-SoJIA vs HS: P = 0.005). We observed a lower Firmicutes/Bacteroidetes ratio in SoJIA patients (3.28 ± 4.47 in Active-SoJIA, 5.36 ± 8.39 in Inactive-SoJIA, and 5.67 ± 3.92 in HS). We also observed decreased abundances of Ruminococcaceae (14.9% in Active-SoJIA, 17.3% in Inactive-SoJIA, and 22.8% in HS; Active-SoJIA vs HS: P = 0.005) and Faecalibacterium (5.1% in Active-SoJIA, 9.9% in Inactive-SoJIA, and 13.0% in HS; Active-SoJIA vs HS: P = 0.000) in SoJIA compared with HS. By contrast, the abundance of Bacteroidaceae was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA and HS groups (16.5% in Active-SoJIA, 12.8% in Inactive-SoJIA, and 9.7% in HS; Active-SoJIA vs HS: P = 0.03). The Spearman correlation analysis revealed a negative correlation between Proteobacteria or Enterobacteriaceae and juvenile arthritis disease activity score on 27 joints (JADAS-27). CONCLUSION The composition of the intestinal microbiota is different in SoJIA patients compared with healthy children. The dysbiosis presents partial restoration in inactive status patients.

Objective This study aimed to investigate the prognostic value of the lateral spread response (LSR) for predicting surgical outcomes following microvascular decompression (MVD) in patients with hemifacial spasm. Methods Seventy-three patients with hemifacial spasm underwent MVD with intraoperative LSR monitoring. Surgical outcomes were evaluated 1 week and 1 year after MVD and correlations between LSR characteristics and surgical outcomes were analyzed. Results The LSR disappeared completely in 61 patients during surgery (Group A; prior to insertion of Teflon felt pledgets in 11, after insertion of pledgets in 50), disappeared partially in nine patients (Group B), and remained unchanged in three patients (Group C). Fifty-five patients showed short-term and 61 patients showed long-term clinical cures during the follow-up period. The short-term and long-term cure rates were significantly higher in Group A than in Group C. There was no correlation between the time of complete LSR disappearance and surgical outcomes. Conclusions Disappearance of the LSR during MVD is correlated with the surgical outcomes. Intraoperative LSR monitoring is a reliable approach for predicting the prognosis of hemifacial spasm following MVD, but the time at which LSR disappears is not a prognostic indicator.

Objective To report the clinical features of patients with systemic lupus erythematosus (SLE) associated with thrombotic thrombocytopenic purpura (TTP). Their diagnosis, treatment, and prognosis were also discussed. Methods A total of 25 TTP-SLE pediatric patients were included in this study. Their clinical symptoms, laboratory findings, disease activity, and renal biopsy were retrospectively reviewed. Results The median age of the patient cohort was 14 years old. Nine patients were first diagnosed with SLE, followed by the diagnosis of TTP-SLE, whereas 15 patients were diagnosed with TTP and SLE concurrently. All the 25 TTP-SLE patients had decreased platelet count and microangiopathic hemolytic anemia. Fever, rash, edema and neurological symptoms were the main clinical symptoms. Fragmentation of erythrocytes on blood smear and increased LDH were found in all patients. Nineteen patients (76%) had impaired renal function. Renal biopsy showed that most of the patients had lupus nephritis class IV (20%) and TMA (20%). 13 patients (52%) were treated with glucocorticoids in combination with immunosuppressive agent, and 10 patients (40%) were treated with plasma exchange combined with glucocorticoids plus immunosuppressive agent. One patient died due to lung infection; others had disease remission. Fifteen patients had follow-up regularly, and their conditions were stable. Conclusion Patients with TTP-SLE often had moderate to severe lupus disease activity. Testing of LDH level and blood smear should be performed when kidney and neurological symptoms arise in children with SLE. The use of combination therapy, glucocorticoids plus immunosuppressive agent, provided satisfactory clinical outcome. Patients with refractory TTP-SLE will also need plasma exchange therapy.

Background We analyze the clinical manifestations and 5 years of follow-up outcomes of children with lupus nephritis (LN) and provide a reference for clinicians. Methods The clinical data of children diagnosed with LN (n=62) from January 2012-2015 were collected and analyzed. Results The median age at the diagnosis was 12.0 years. The female to male ratio was 3.4:1. The most prevalent clinical features were mucocutaneous involvement and hematological involvement. Renal biopsy was performed on 38 patients. Class IV and class V were the most common findings. The lupus activity was improved markedly after 3 months treatment. The rate of survival was 98.3% in 5 years. The most common side effects of corticosteroid and other immunosuppressive agent drug treatment were corticosteroid-related hypertension and high intraocular pressure. The rate of cataracts, osteoporotic fracture, and visual field defects increased as the treatment progressed. Especially, the incidence of visual field defects in children is higher than adults. Conclusions The LN children showed a good prognosis. During the follow-up process, the adverse drug reactions, such as hormone-related hypertension and ocular hypertension, especially the visual field defects caused by hydroxychloroquine, cannot be excluded. However, multicenter long term follow-up studies are essential to substantiate the current data.

Background: Targeted urinalysis has been suggested to improve screening efficiency in adults. However, there is no well-defined target population in children yet, with limited information on the risk factors for urinalysis abnormalities.Methods: Children from infants to 17 years old were randomly selected. Dipstick urinalysis was initially performed. Among those who were abnormal, a repeat dipstick or dipstick with microscopic urinalysis was performed for confirmation.Results: In total, 70,822 children were included, with 37,866 boys and 32,956 girls. Prevalence of abnormal urinalysis was 4.3%. Age was significantly associated with abnormal urinalysis, with the highest prevalence among 12–14-year-olds. Girls were 2.0 times more likely to exhibit abnormalities. Compared with children whose guardians had a college degree or higher, those whose guardians had a high school degree or lower had a higher likelihood of abnormalities. Geographic location was also associated with abnormal results.Conclusion: Girls, children aged 12–14 years old, and children whose guardians had a low educational level and children in certain geographic locations were significantly associated with abnormal urinalysis. Identification of children at high risk would contribute to targeted urinalysis screening.

Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures (SRS) and comorbidities. Kindling through repetitive brief stimulation of a limbic structure is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling over a period up to a few months can induce SRS, which may simulate slowly evolving epileptogenesis of temporal lobe epilepsy. Currently, electroencephalographic (EEG) features of SRS in rodent models of extended kindling remain to be detailed. We explored this using a mouse model of extended hippocampal kindling. Intracranial EEG recordings were made from the kindled hippocampus and unstimulated hippocampal, neocortical, piriform, entorhinal, or thalamic area in individual mice. Spontaneous EEG discharges with concurrent low-voltage fast onsets were observed from the two corresponding areas in nearly all SRS detected, irrespective of associated motor seizures. Examined in brain slices, epileptiform discharges were induced by alkaline artificial cerebrospinal fluid in the hippocampal CA3, piriform and entorhinal cortical areas of extended kindled mice but not control mice. Together, these in vivo and in vitro observations suggest that the epileptic activity involving a macroscopic network may generate concurrent discharges in forebrain areas and initiate SRS in hippocampally kindled mice.

Background Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease caused by mutations in the ADA2 gene. Few Chinese cases have been reported. We describe and compare the clinical features, genotypes, and treatments of Chinese DADA2 patients and non-Chinese patients. Methods Primary immunodeficiency disease panel or whole-exome sequencing was performed for suspected cases, and assays for adenosine deaminase 2 (ADA2) enzyme activity were also carried out for the patients and their parents. Case reports of Chinese and non-Chinese patients with DADA2 were searched in PubMed and Chinese national databases. Results Seven unrelated children from China with DADA2 were included in our study. Five were identified at Peking Union Medical College Hospital, and two had been reported previously (1 on PubMed and 1 in Chinese literature). Fourteen mutations in ADA2 were identified, 7 of which have not previously been reported in non-Chinese patients. Four children who underwent enzymatic analysis had lower ADA2 activity compared with their parents. Phenotypic manifestations included fever, skin symptoms, vasculitis, and neurologic involvement. Treatments varying from steroids, immunosuppressants, and tocilizumab, anti-TNF therapy and hematopoietic stem cell transplantation (HSCT) were effective depending on phenotype and severity. Conclusion This study includes the largest number of Chinese DADA2 patients to date. We recommend the combination of enzymatic analysis with gene screening to confirm the diagnosis. Different genotypes were observed among Chinese DADA2 patients; most phenotypes were similar to those of non-Chinese DADA2 patients, except for growth retardation. Disease remission might not be achieved with anti-IL-6 therapy.

Background The aim of this study was to assess the characteristics of hip fracture during the novel coronavirus (COVID-19) epidemic.Method Hip-facture patients undergoing surgery from January 26 to March 31, 2020 (group A) and from January 26 to March 31, 2019 (group B) were retrospectively included. The durations from injury onset to hospital discharge, hospitalization cost, comorbidity, and complications of patients in the two groups were collected. The daily activity and light exposure time, and medical treatment interruption of patients in group A before and during their self-quarantine were also collected. In addition, the reasons for those with hospital admission delay were inquired.Results During the COVID-19 epidemic, patients with hip fracture was increased by 9 cases (69.23%). Patients in group A underwent an over 20-hour longer duration from the injury onset to hospital, an over 3-day longer hospitalization stay, and more hospitalization cost of over 4-thousand yuan compared with those for patients in group B (P < 0.05). The self-quarantine led to reduced daily activities (P Conclusion During the COVID-19 epidemic period, the prevention and management of hip-fracture for the elderly require more attention for the public and medical care personnel.

Objective: We designed and performed a network meta-analysis to compare the clinical outcomes among the 5 surgeries—anterior cervical corpectomy and fusion (ACCF), anterior controllable antedisplacement fusion (ACAF), laminoplasty (LP), laminectomy (LC), and posterior decompression with instrumented fusion (PDF)—for patients with cervical spondylosis related to the ossification of the posterior longitudinal ligament (OPLL). Methods: Databases, including PubMed, EMBASE, Cochrane Library, Google Scholar, and Web of Science (firstly available-2019) were selected for literature search. We performed a network meta-analysis with the included studies. A Newcastle-Ottawa scale was employed to assess the study quality of the included studies. Results: Total 23 studies with 1516 patients were included in our analysis. We found that ACCF achieved the most improvement in the Japanese Orthopaedic Association Scores and excellent and good recovery rate, ACAF achieved the best improvement of the improvement rate and lordosis. LP got the best operative time and blood loss. Conclusions: Our results suggested that both anterior (ACCF and ACAF) and posterior (LP, LC, and PDF) procedures have their strengths and weaknesses. Clinicians need to select the most appropriate surgery with a comprehensive consideration of the clinical condition of each patient with OPLL-related cervical spondylosis.

Objective: Monogenic autoinflammatory diseases (AIDs) are inborn disorders caused by innate immunity dysregulation and characterized by robust autoinflammation. We aimed to present the phenotypes and genotypes of Chinese pediatric monogenic AID patients. Methods: A total of 288 pediatric patients clinically suspected to have monogenic AIDs at the Department of Pediatrics of Peking Union Medical College Hospital between November 2008 and May 2019 were genotyped by Sanger sequencing, and/or gene panel sequencing and/or whole exome sequencing. Final definite diagnoses were made when the phenotypes and genotypes were mutually verified. Results: Of the 288 patients, 79 (27.4%) were diagnosed with 18 kinds of monogenic AIDs, including 33 patients with inflammasomopathies, 38 patients with non-inflammasome related conditions, and eight patients with type 1 interferonopathies. Main clinical features were skin disorders (76%), musculoskeletal problems (66%), fever (62%), growth retardation (33%), gastrointestinal tract abnormalities (25%), central nervous system abnormalities (15%), eye disorders (16%), ear problems (9%), and cardiopulmonary disorders (8%). The causative genes were ACP5, ADA2, ADAR1, IFIH1, LPIN2, MEFV, MVK, NLRC4, NLRP3, NLRP12, NOD2, PLCG2, PSMB8, PSTPIP1, TMEM173, TNFAIP3, TNFRSF1A, and TREX1. Conclusions: The present study summarized both clinical and genetic characteristics of 18 kinds of monogenic AIDs found in the largest pediatric AID center over the past decade, with fever, skin problems, and musculoskeletal system disorders being the most prevalent clinical features. Many of the mutations were newly discovered. This is by far the first and largest monogenic AID report in Chinese pediatric population and also a catalog of the phenotypic and genotypic features among these patients.

Background Several complications like calcinosis, interstitial lung disease (ILD) or malignancy, are primary causes leading to poor outcomes in idiopathic inflammatory myopathies (IIM) patients. Specific antibodies might help to indicate the occurrence or absence of these complications. Objective The aim of this study was to evaluate the association of anti-nuclear matrix protein 2 antibody (anti-NXP2) with calcinosis, ILD and malignancy in IIM patients. Methods Two investigators independently searched literature about the relation of anti-NXP2 with calcinosis, ILD, malignancy in IIM patients in PubMed, EMBASE, Web of Science databases, then selected eligible articles and extracted data from the included studies. The association between anti-NXP2 and these complications was assessed by odds ratios (OR) and 95% confidence intervals (95% CI). Further quantitative meta-analysis, subgroup analysis, sensitivity analysis and publication bias analysis were conducted with STATA 14.0 software (Stata Corp.; College Station, Texas, USA). A fixed-effects model (the Mantel-Haenszel method) was employed when I2 Results Twenty cohorts with 3064 IIM patients were included in this meta-analysis, among which 9 were about calcinosis in adults, 6 about calcinosis in juvenile patients, 9 about ILD in adults, 3 about ILD in juvenile patients, while 13 about malignancy in adult patients. Anti-NXP2 was more common in patients with calcinosis than those without calcinosis (pooled OR = 4.00, 95% CI: 2.65–6.06 in adults; pooled OR = 1.62, 95% CI: 1.14–2.30 in juvenile patients). On the contrary, this antibody was less common in adult patients with ILD than those without ILD (pooled OR: 0.33, 95% CI: 0.19–0.56). No significant difference concerning the incidence of anti-NXP2 antibody was found in IIM patients between those with and without cancer (pooled OR = 1.42, 95% CI: 0.69–2.91). Conclusion The present study indicates that anti-NXP2 autoantibody is a risk factor for development into calcinosis both in adult and juvenile patients, while a protective factor for ILD in adult patients. Anti-NXP2 had no relation with malignancy in adult patients.

In teleost fishes, miR-430 has several paralogs and is widely required for mesoderm formation and gonad development. However, the functions of miR-430 in skin pigmentation have not been completely elucidated. To understand the functions of miR-430 in color formation, we analyzed the conserved characteristics of miR-430 family in teleost, detected miR-430 family spatial and temporal expression patterns, verified the target differences between miR-430a and miR-430b, identified the phenotypic changes by overexpressing miR-430b in vivo and assessed the roles of miR-430b in coloration by analyzing the genes associated with pteridine and carotenoid pigment metabolism. The results showed that miR-430a and miR-430b were highly conserved in teleosts and that miR-430b was intensively expressed in skin, fins and scales comparing with miR-430a. Target verification analysis showed that miR-430b displayed significant repressive effects on scarb1 compared with miR-430a. In addition, overexpression of miR-430b led to diminished red intensity by decreasing skin carotenoid content and xanthophores/erythrophores density in scales. Accompanying the color dilution, the mRNA and protein levels of scarb1 were markedly inhibited by increased miR-430b, and several genes correlated with carotenoid metabolism also underwent corresponding modification. However, the contents of pteridine pigments and related genes experienced only limited changes. These findings suggest that miR-430b can improve skin pigmentation by blocking the expression of scarb1, resulting in carotenoid metabolism dysregulation and chromatophores density reduction.

Introduction. Epilepsy is a disease characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition. Temporal lobe epilepsy (TLE) is the most common and often drug-resistant type of epilepsies in the adult and aging populations and has greatly diverse in etiologies and electro-clinical manifestations. Kindling through repeated brief stimulation of limbic structures has long been used as a model of TLE. While classic kindling in a few weeks does not induce spontaneous recurrent seizures (SRS), extended kindling is able to induce SRS in several animal species. The SRS induction by extended kindling is generally not associated with gross brain injury, but rather a loss of subgroups of GABAergic interneurons in the hippocampal hilar region. The lack of observed gross brain injury in extended kindled animals is different from post status epilepticus models in which SRS emergence is accompanied with pronounced brain damage. As such the extended kindling model may help explore epileptogenesis in the absence of major brain pathology as is seen in many patients with TLE. To data, there is limited insight about EEG characteristics of SRS in rodent models of extended kindling. We therefore attempted to provide more information in this area using a mouse model of extended hippocampal kindling (Song et al., 2018; Liu et al., 2019; Frontier Pharmacology). Methods. Male C57 black mice ages 11–13 months were operated to implant intracranial electrodes. Each mouse was implanted with two pairs of bipolar electrodes, one in the hippocampal CA3 for kindling stimulation and local recordings and another in contralateral/ipsilateral hippocampal CA3, dorsomedial thalamus, parietal cortex or entorhinal cortex. Hippocampal kindling (60 Hz for 2 sec) was applied twice daily, and SRS were detected by 24-hour EEG-video monitoring. Age-match mice that received similar electrode implantation and twice daily handling manipulation but not kindling were used as controls. Brain histological examinations were performed in a subset of mice to verify the location of implanted electrodes and to examine potential gross brain lesion. Results. (1) SRS were observed from 47 mice following 80–140 kindling stimulation; no spontaneous seizure was detected in 12 control mice. (2) SRS remained detectable in individual mice up to 4 months after termination of the kindling stimulation. SRS incidences varied in a range of 2–14 events per day but inter-SRS intervals were ≤2 hours for about 65% of SRS events. (3) Most of SRS were featured with EEG ictal discharges and concurrent motor seizures at the Racine scale 3–5. SRS that presented EEG ictal discharges without or with concurrent motor behaviors at the Racine scale 1–2 were also noticeable, particularly in mice with implanted electrode in the dorsomedial thalamus. (4) In ≥1500 SRS events examined, nearly all EEG ictal discharges presented low-voltage signals at onset and such ictal onset appeared to concur in the kindled CA3 and unkindled site despite the latter targeted to different brain structures. (5) CA3 and cortical EEG ictal discharges were not substantially affected by intra-peritoneal injection of lorazepam (a benzodiazepine positive GABAa receptor modulator) but concurrent severe motor seizures were greatly suppressed. Summary. We suggest that epileptogenic network activity encompassing multiple forebrain areas may be responsible for SRS initiation in the mouse model of extended hippocampal kindling. Subcortical structures involving the dorsomedial thalamic circuitry may play an important role in manifestation and/or control of severe motor seizures in this model. Support. EpLink – The Epilepsy Research Program of the Ontario Brain Institute and Natural Sciences and Engineering Research Council of Canada.

// Mingxu Luo 1, * , Hongmei Song 2, * , Gang Liu 1, * , Yikai Lin 3 , Lintao Luo 1 , Xin Zhou 1 and Bo Chen 1, 4 1 Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China 2 Department of Oncology, Renmin Hospital of Shiyan, Hubei University of Medicine, Shiyan, China 3 Department of Radiology, The First Affiliated Hospital of Xiamen University, Xiamen, China 4 Teaching and Research Section of Surgery, The First Clinical College of Fujian Medical University, Fuzhou, China * Co-first authors Correspondence to: Bo Chen, email: chenbo7892@xmu.edu.cn Keywords: lymph node staging, gastric cancer, diffusion weighted imaging, positron emission tomography/computed tomography Received: June 02, 2017 Accepted: September 08, 2017 Published: September 19, 2017 ABSTRACT The diagnostic values of diffusion weighted imaging (DWI) and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for N-staging of gastric cancer (GC) were identified and compared. After a systematic search to identify relevant articles, meta-analysis was used to summarize the sensitivities, specificities, and areas under curves (AUCs) for DWI and PET/CT. To better understand the diagnostic utility of DWI and PET/CT for N-staging, the performance of multi-detector computed tomography (MDCT) was used as a reference. Fifteen studies were analyzed. The pooled sensitivity, specificity, and AUC with 95% confidence intervals of DWI were 0.79 (0.73–0.85), 0.69 (0.61–0.77), and 0.81 (0.77–0.84), respectively. For PET/CT, the corresponding values were 0.52 (0.39–0.64), 0.88 (0.61–0.97), and 0.66 (0.62–0.70), respectively. Comparison of the two techniques revealed DWI had higher sensitivity and AUC, but no difference in specificity. DWI exhibited higher sensitivity but lower specificity than MDCT, and 18 F-FDG PET/CT had lower sensitivity and equivalent specificity. Overall, DWI performed better than 18 F-FDG PET/CT for preoperative N-staging in GC. When the efficacy of MDCT was taken as a reference, DWI represented a complementary imaging technique, while 18 F-FDG PET/CT had limited utility for preoperative N-staging.

To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC).Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively. Tumor growth and radioresistance were also evaluated using xenograft models created in nude mice.eEF2K expression was higher in ESCC tissues compared with matched non-tumor tissues (P0.05). Proliferation was increased in eEF2K overexpressing cells compared with controls (P0.05), while silencing eEF2K reduced cell proliferation (P0.05). Furthermore, lower levels of eEF2K expression correlated with slower migration and invasion rates (P0.05), while higher levels of eEF2K expression with faster migration and invasion rates (P0.05). eEF2K overexpression resulted in radioresistance and radiation-induced autophagy, and reduced radiation-induced apoptosis compared with controls, but silencing eEF2K promoted radiosensitivity and apoptosis, and reduced autophagy. In addition, eEF2K overexpression promoted the tumor growth in vivo (P0.01). Combined treatment of NH125 (a pharmacological inhibitor of eEF2K) and radiation was more effective at delaying xenograft tumor growth than NH125 and radiation alone (P0.05).eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity.

Purpose To evaluate the diagnostic accuracy of aneurysm detection and the fidelity of morphologic characterization of three-dimensional (3D) time-of-flight (TOF) magnetic resonance (MR) angiography at 3.0 T in patients with a Glasgow coma score of 15 and noncontrast material-enhanced computed tomography (CT) findings that showed acute nontraumatic subarachnoid hemorrhage. Materials and Methods The institutional review board approved this prospective study, and patients provided informed consent. A total of 277 patients who had not experienced trauma but in whom nonenhanced CT showed subarachnoid hemorrhage, who had a Glasgow coma score of 15, and who underwent both 3D TOF MR angiography and digital subtraction angiography (DSA) (the reference standard) were included. Three observers who were blinded to clinical and DSA results independently analyzed all 3D TOF MR angiographic data sets. The receiver operating characteristic curve was applied to analysis of the detection of aneurysms with 3D TOF MR angiography by using patient- and aneurysm-based evaluations. Multivariate logistic regression analysis was performed to identify aneurysm-specific variables, including size, shape (daughter sac/lobulation/margin), neck width (wide if > 4 mm or if fundus-to-neck ratio was < 2), and relation to adjacent artery, that significantly affected morphologic assessment with 3D TOF MR angiography. Results Aneurysms were depicted with DSA in 225 patients. In patient- and aneurysm-based evaluations, respectively, 3D TOF MR angiography yielded accuracies of 96.8% (268 of 277) and 96.6% (309 of 320), sensitivities of 98.2% (219 of 223) and 98.1% (260 of 265), specificities of 91% (49 of 54) and 89% (49 of 55), positive predictive values of 97.8% (219 of 224) and 97.7% (260 of 266), and negative predictive values of 92% (49 of 53) and 91% (49 of 54). Accuracy of display of morphologic features was 92.5% (236 of 255) for size, 86.3% (220 of 255) for neck width, 94.5% for shape (241 of 255), and 96.9% (247 of 255) for relationship to adjacent vessel. Width of aneurysm neck was the only variable that significantly affected the morphologic assessment of 3D TOF MR angiography (odds ratio, 0.378; 95% confidence interval: 0.337, 8.347; P = .004). Conclusion Three-dimensional TOF MR angiography can accurately depict cerebral aneurysms and accurately display their morphologic features in stable patients with subarachnoid hemorrhage and a Glasgow coma score of 15. © RSNA, 2017.

Background: Familial Mediterranean fever (FMF) is an inherited auto-inflammatory disorder and is extremely rare in Chinese. This study aimed to investigate the demographic, clinical, and genetic features of FMF in a series of Chinese pediatric patients. Methods: This was a retrospective case series of children with recurrent febrile or inflammatory episodes and referred to the Peking Union Medical College Hospital between 06/2013 and 06/2018. All suspected patients were genetically diagnosed and met the Tel-Hashomer criteria for FMF. Demographic, clinical, genetic, and treatment characteristics were collected. Descriptive statistics were used. Results: Eleven patients were included (seven boys and four girls). The median age at the time of disease onset was 7.1 (range, 3–12) years, while the median age at diagnosis was 10.9 (range, 6–15) years. The median delay in diagnosis was 2.1 years (range, 6 months to 6.7 years). Fever (100%, 11/11) was the most common symptom, followed by joint pain (63.6%, 7/11), rash (54.5%, 6/11), abdominal pain (36.4%, 4/11), and oral ulcers (18.2%, 2/11), without evidence of amyloidosis. C-reactive protein (81.8%, 9/11) and erythrocyte sedimentation (90.9%, 10/11) were increased during attacks. All patients harbored one to five different MEFV mutations, with E148Q and L110P being the most frequent. A novel non-synonymous mutation F636Y in exon 10 was discovered. Favorable responses to colchicine was observed in all six treated patients. Conclusion: The most common variants in our study were E148Q and L110P. F636Y may found for the first time. Colchicine led to favorable responses in all treated patients.

Background Primary immunodeficiency diseases (PIDs) patients may show systemic lupus erythematosus (SLE)-like autoimmunity disorders, such as cytopenias, as well as polyarthritis, which leads to concerns of misdiagnosis. We diagnosed three RALD cases between 2015 and 2018, who were suspected as SLE and summarized clinical characteristics. Methods We collected and analyzed the clinical data of the 3 cases. DNA was extracted from the patients’ and their parents’ peripheral blood as well as oral mucosa cells, hair follicles, and nails. Genes were detected with the application of gene trapping high-throughput sequencing using PIDs panel and suspicious gene or mutation was further verified by Sanger sequencing. Results 1. Clinical features: On the one hand, the patients presented with severe thrombocytopenia, facial erythema, arthritis, positive autoantibodies and other manifestations, supporting the diagnosis of SLE. On the other hand, symptoms including early onset ages, recurrent infections, lymphadenopathy, hepatosplenomegaly, monocytosis and hypergammaglobulinemia, were common observed in PIDs. 2. Gene analysis: NRAS mutations (c.38G > A, p.G13D or c.37G > T, p.G13C) were found in the blood of the patients. Besides, the same set of mutations was detected in buccal mucosa of patient 1 and nails of patient 3 while the frequency was much lower. However, no mutation was found in other tissues or in their parents’ blood. Consequently, they were NRAS somatic mutated RALD. Conclusions For those early-onset SLE-like patients with predominant hematologic disorders, monocytosis, recurrent infectious history, accompanied with hepatosplenomegaly and lymphadenopathy, a genetic screening of PIDs might be required.

Ubiquitinases are a select group of enzymes that modify target proteins through ubiquitination, which plays a crucial role in the regulation of protein degradation, location, and function. B lymphocytes that originated from bone marrow hematopoietic stem cells (HSC), exert humoral immune functions by differentiating into plasma cells and producing antibodies. Previous studies have shown that ubiquitination is involved in the regulation of the cell cycle and signal transduction important for B lymphocyte development and function. In this review, how ubiquitinases regulate B cell development, activation, apoptosis, and proliferation is discussed, which could help in understanding the physiological processes and diseases related to B cells and also provides potential new targets for further studies.

OBJECTIVES: Although it is widely believed that China is facing a major shortage of pediatricians, the real situation of the current national status of pediatric human resources and their working conditions has not been evaluated to date. METHODS: We administered a survey to 54 214 hospitals from all 31 provinces in mainland China from 2015 to 2016. Hospital directors of all secondary and tertiary hospitals with pediatric services and a random sample (10%) of primary hospitals provided information on number of pediatricians and their educational levels, specialties, workloads, dropout rates, and other hospital characteristics. A data set of medical resources and socioeconomic information regarding each region (1997–2016) was constructed from the Chinese National Statistics Bureau. The Gini coefficient was used to describe the geographical distributions of pediatricians and hospitals. RESULTS: There were 135 524 pediatricians in China or ∼4 pediatricians per 10 000 children. Pediatricians’ average educational level was low, with ∼32% having only 3 years of junior college training after high school. The distribution of pediatricians was extremely skewed (Gini coefficient 0.61), and the imbalance of highly educated pediatricians was even more skewed (Gini coefficient 0.68). The dropout rate of pediatricians was 12.6%. Despite an increase in the Chinese government’s financial investment in health over the last decade, physicians have been burdened with a greater workload. CONCLUSIONS: Uneven development of the pediatric care system, inadequately trained pediatricians, low job satisfaction, and unmet demand for pediatric care are the major challenges facing China’s pediatric health care system.

Background: Genetically susceptibility was essential in pathogenesis of systemic juvenile idiopathic arthritis (SJIA). Objectives: To find out whether MEFV mutations contributed to the occurrence of SJIA and study the association of MEFV mutations with systemic juvenile idiopathic arthritis (SJIA) patients’ disease severity. Methods: SJIA children diagnosed based on the ILAR criteria[1] and followed up for at least 6 months between January 2011 and July 2018 were enrolled. Meta-analysis was performed to evaluate the contribution of MEFV mutations to SJIA susceptibility. All included children were divided into three groups by presence and number of MEFV mutations, namely, those without MEFV mutation, the one mutation group, and those with more than one mutation. Demographic and clinical characteristics, as well as disease severity were compared among these groups. Disease severity was evaluated with the following three items, i.e., average duration of use of each drug, the proportion of disease activity duration and relative relapse rate. Kaplan-Meier curves and log rank test were used to estimate the probability of the first relapse. Results: Eighty-nine patients met the ILAR criteria, among which 55 patients were eligible for further analysis. The MEFV mutations of our subjects primarily existed in exons 2 and 3. No significant difference were found in frequency of each mutation between SJIA children and healthy controls. Meta-analysis demonstrated that M694V was a risk factor for SJIA (pooled OR: 7.13, 95% CI: 3.01-16.89). Comparing with the one mutation group, biologics were used more frequently in those without or with more than one mutation in MEFV (p=0.017). Moreover, the proportion of disease activity duration was significantly lower in the one mutation group than the other two groups (p=0.028 and 0.002 respectively). Conclusion: The mutation M694V in MEFV contributed to occurrence of SJIA. SJIA patients carrying one heterozygous mutation in MEFV tend to be less severe, which might be attributed to E148Q. References [1] Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis: Second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390-2. Disclosure of Interests: None declared

Background The prevalence of cytomegalovirus in China is high and the infection could result in disastrous consequences. Cellular immunity is the main mechanism for virus controlling. We explored the performance of cytomegalovirus antigen-specific enzyme-linked immunospot assay in patients with different infection states in endemic area. Methods Twenty-eight patients with reliable results were included in statistical analysis. Peripheral blood mononuclear cells were extracted and were stimulated by cytomegalovirus phosphoprotein 65 or immediate early protein-1 antigen respectively. Spot forming cells (SFCs) were counted to evaluate the cellular immune response elicited by antigens. Results Spots could be clearly displayed, and evenly dispersed with a clean background. The numbers of SFCs were 0 [0–0], 426 [210–601] and 230 [57–513] for uninfected individuals (n = 7), latently infected patients (n = 11) and actively infected patients (n = 10) respectively, which were statistically different. The number of SFCs stimulated by phosphoprotein 65 was significantly higher than that by immediate early protein-1. Conclusions The number of SFCs was significantly different among patients with different infection state. The stimulatory effect of phosphoprotein 65 was better than that of immediate early protein-1.

Background The clinical features, angiographic findings, and outcomes have not been compared between pediatric and adult patients with Takayasu arteritis (TA) with coronary involvement. Methods Of 1056 consecutive patients with TA hospitalized and followed from 1990 to 2018 in our hospital, 38 patients including 9 children and 29 adults (mean age at diagnosis of 14.3 ± 3.3 years and 38.6 ± 12.0 years, respectively) were diagnosed with coronary artery involvement by imaging. Clinical manifestations, coronary lesion characteristics, and outcomes were compared between the pediatric and adult patients. Results Compared with adults, pediatric patients with TA with coronary involvement had a significantly shorter disease duration (median, 2 months; interquartile range [IQR], 1-38 vs median, 48 months [IQR, 18-90], P = 0.019) and higher disease activity score (median, 3 [IQR, 2-4] vs median, 2 [IQR, 1-3], P = 0.013) on the first positive coronary assessment. Although all recruited patients except 1 child had coronary stenosis, coronary aneurysmal dilation was found in 6 patients and was more frequent in children than in adults (55.6% vs 3.4%, P = 0.001). Moreover, the children with coronary aneurysmal dilation had a higher incidence of dilation in large vessels than children without aneurysmal dilation (80.0% vs 0%, P = 0.048). Conclusion Pediatric patients with TA with coronary involvement had higher inflammation status and were more prone to coronary aneurysmal dilation on the first positive coronary assessment compared with adults. Dilation in the aorta and its major branches might be an indicator of coronary aneurysmal dilation in these pediatric patients.

Purpose: To identify pathogenic gene variants in the NOD2 gene and assess the clinical features of a cohort of Chinese patients affected with Blau syndrome.Methods: Eight patients from seven unrela...

As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer.

Mesial temporal lobe epilepsy is generally manifested as central nervous system disorder, emotional disturbances, and visceral discomfort. We present the case of an elderly male patient with mesial temporal lobe epilepsy presenting with rising epigastric sensation as the only manifestation. A 60-year-old male patient who had been regularly suffering from episodic epigastric sensations three to seven times every day was admitted to our hospital. 'Rising air' initiated from epigastria, ascending to his chest, and terminated in the throat. Brain MRI showed sclerosis of the right hippocampus and enlargement of the right temporal horn. Video electroencephalography showed that the seizure was associated with a high-amplitude spike and slow wave, originating from the right anterior temporal region and extending to the leads in the right hemisphere. Extensive gastrointestinal and cardiothoracic investigations showed no abnormality, and so an underlying seizure disorder was suspected. The patient was prescribed a low dose of carbamazepine of 200 mg daily and was discharged the next day. A repeat video electroencephalography confirmed the satisfactory efficacy of the treatment. During the follow-up period of 22 months, there was no reappearance of epilepsy. Primary physicians, especially gastroenterologists, should be acquainted with the manifestations of simple partial seizures to avoid any dispensable medical examinations, even maltreatments.

Background:Takayasu arteritis (TA) is the most prevalent large-vessel vasculitis in children. Patients with TA have a high mobidity and mortality.It remains a therapeutic challenge because corticosteroids monotherapy can rarely cure TAK and the relapse rate is high during GC tapering.Objectives:The aim of this study is to investigate the efficacy and safety of tocilizumab (TCZ)in Chinese children with Takayasu arteritis(TAK).Methods:We retrospectively studied 6 TAK children treated with TCZ in our hospital from July 2017 to October 2018. The demographic and clinical data, laboratory examination results and vascular imaging data were collected.Results:Six pediatric patients with critical or refractory TAK treated with TCZ were analyzed, including 3 males and 3 females.The diagnosis age was ranging in age from 2 to 13 years(median age:7 years).Three patients were initially treated with TCZ and Mycophenolate Mofetil(MMF) as the first-line regimen without corticosteroid or with a quite rapid GC taper duration,two of which had lifte-threatening coronary arteries involved and heart failure.The other three paitients were swcithed to TCZ from conventional disease modifying anti-rheumatic drugs (DMARDs) or other biologics due to being refractory to them and recurrent relapses.Four patients were given TCZ at 4 weeks regular intervals for 10 to 22 months,while two patients withdrew TCZ because of disease deterioration and unbearable abdominal or chest pain after the second dose.After 6 months follow-up,four patients experienced significant clinical and biological improvement with angiographically progression in one patient. A corticosteroid-sparing effect is obvious. Drug-related side effects occur in 1 patients manifesting as a mild elevated liver fuction. Neither neutropenia nor infection was observed.Conclusion:Our study shows a clinical, biological, and radiological response in patients with refractory TAK treated with TCZ.References :[1]Hellmich B, Agueda A, Monti S,et al.2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 2019;0:1–12. doi:10.1136/annrheumdis-2019-215672.[2]BravoMancheño B, Perin F, Guez Vázquez Del ReyMDMR, García Sánchez A, Alcázar Romero PP. Successful tocilizumab treatment in a child with refractory Takayasu arteritis.Pediatrics 2012;130(6):e1720-724.[3]Goel R, Danda D, Kumar S, Joseph G. Rapid control of disease activity by tocilizumab in 10 «difficult-to-treat» cases of Takayasu arteritis. Int J Rheum Dis 2013;16(6):754–61.[4]Cañas CA, Cañas F, Izquierdo JH, Echeverri A-F, Mejía M, Bonilla-Abadía F, et al. Efficacy and safety of anti-interleukin 6 receptor monoclonal antibody (tocilizumab) in Colombian patients with Takayasu arteritis. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis 2014;20(3):125–9.[5]Batu ED, Sönmez HE, Hazirolan T, Özaltin F, Bilginer Y, Özen S. Tocilizumab treatment in childhood Takayasu arteritis: case series of four patients and systematic review of the literature. Semin Arthritis Rheum 2017 Feb;46(4):529–35.Disclosure of Interests:None declared

Background:Familial cold autoinflammatory syndrome 3 (FCAS3) is an autoinflammatory disease (AID) caused by mutation of the PLCG2 gene, which has not been reported in China. We will report 2 cases of Chinese FCAS3 patients with no claimed family history, but we found the same mutations in a parent during their genetic analysis. After further inquiry of the parent’s medical history, we confirmed that actually, they were two FCAS3 families. Through a literature review, we found that the clinical features of Chinese patients are milder than foreign countries, and their symptoms are concealed and may be ignored, resulting in mistakes in family history collecting.Objectives:To summarize the genetic and clinical features of Chinese FCAS3 patients and to provide diagnostic recommendations for the disease.Methods:Two suspected AID children with recurrent fever and urticaria were enrolled in this study. Clinical data and family history were collected, and genetic analysis was performed by next-generation sequencing (PID panel or WES) and Sanger-based validation. Literature was reviewed from PubMed, CNKI, and Wanfang Database.Results:The two children were both diagnosed to be FCAS3 with PLCG2 mutation. The clinical manifestations of 2 children were recurrent fever, urticaria, and increased ESR and CRP. Case 1 has a paternal, and Case 2 has a maternal heterozygous mutation in the PLCG2 gene, while both had claimed without a family history. Further inquiry showed the two parents used to have a fever with urticaria. By comparing with foreign literature, we found our patients were milder than abroad patients. Large fragment deletions were relatively more common in foreign patients.Conclusion:We reported the case of FCAS3 in China for the first time. Their genotype and phenotype were different from foreign patients. Their symptoms are mild, and heterozygous mutations are more common than foreign patients, which are the main differences. The difference in mutation type may be the reason for different clinical manifestations. Besides, both two families showed a trend of more severe clinical features in the next generation. As the symptoms of the elders were not obvious and may be ignored, it caused trouble for the genetic diagnosis. Therefore, family history should be collected carefully. For rashes and fevers, which are not too severe in overall symptoms, care should be taken about the possibility of AIDs. Genetic testing can help to make a definite diagnosis.Table 1.Descriptive charecteristics of the patients with FMF, n=474VariableCompliant(n=230)Noncompliant (n=244)P valueGender of patient (F)142(61.7)147(60.2)0.73Age, years*35(28-42.5)34(27-44.2)0.88Being Married152(66.1)146(59.8)0.15Disease duration, years*22(14-31)22(15-31)0.71Number of index flare*within last 12-month6.7(1-10)5(3-10)Family historyof parents54(23.5)39(16.0)0.04Family historyof sibling73(32.9)102(43.4)0.02Comorbid disease presence73(31.7)55(22.5)0.02TreatmentColchicine230 (94.1)180(78.6)Anakinra&Canakinumab134(5.3)49(21.4)Colchicine response presence127(55.2)126(52.3)0.52Drug using except FMF74(32.2)44(18.0)Presence of 2 attacks except fever90 (39.1)68(27.9)0.009Chronic peripheral arthritis16(7.0)7(2.9)0.03Amyloidosis18(7.8)9(3.7)0.05Proteinuria23(10.8)8(3.6)0.004Adequate medical care161(70.0)132(54.8)ISSF severity score*3(2-4)3(2-4)0.02ADDI index*1(0-1)1(0-1)0.05References:[1]Pathak S, Mcdermott M F, Savic S. Autoinflammatory diseases: update on classification diagnosis and management[J]. Journal of Clinical Pathology, 2017, 70(1):1-8.[2]Broderick, L., Hereditary Autoinflammatory Disorders: Recognition and Treatment. Immunol Allergy Clin North Am, 2019. 39(1):13-29.[3]Milner, Joshua D. PLAID: A Syndrome of Complex Patterns of Disease and Unique Phenotypes[J]. Journal of Clinical Immunology, 2015, 35(6):527-530.[4]Picard C, Gaspar H B, Al-Herz W, et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity[J]. Journal of Clinical Immunology, 2017, 38(Suppl 1):96-128.[5]Ombrello M J, Remmers E F, Sun G, et al. Cold Urticaria, Immunodeficiency, and Autoimmunity Related to PLCG2 Deletions[J]. New England Journal of Medicine, 2012, 366(4):330-8.[6]Zhou Q, Lee GS, Brady J, et al. A Hypermorphic Missense Mutation in PLCG2, Encoding Phospholipase Cγ2, Causes a Dominantly Inherited Autoinflammatory Disease with Immunodeficiency[J]. American Journal of Human Genetics, 2012, 91(4).[7]Neves, J.F., et al., Novel PLCG2 Mutation in a Patient with APLAID and Cutis Laxa. Front Immunol, 2018. 9: 2863.[8]Mcdermott M F, Aksentijevich I, Galon J, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes[J]. Cell, 1999, 97(1):133-144.Disclosure of Interests:None declared

Background The coagulation status of patients with systemic lupus erythematosus (SLE) is quite complicated, and there are currently no simple efficient methods for its evaluation. We explored the feasibility of thromboelastography (TEG) for this purpose. Methods Paediatric SLE patients were divided into different groups based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. TEG parameters were compared between patients and healthy controls (HCs) and in patients by level of disease activity. Six patients treated with pulse methylprednisolone were also analysed before and after treatment. Results Thirty-nine children with SLE were enrolled, one of whom had bleeding and three of whom had thrombosis. The four TEG tracings of these four children were different. The TEG parameters of the patients (except the four children mentioned above) showed hypercoagulability, shortened R and K times, increased α-angle and maximum amplitude (MA), decreased LY30 and increased clot index (CI) compared with the parameters of the HCs ( P Conclusions Compared with the HCs, paediatric SLE patients showed hypercoagulability caused by increased coagulation and decreased fibrinolysis. These coagulation changes were associated with disease activity. TEG could be a potential tool for evaluating the coagulation status of children with SLE.

Objective: It has been established that reduced vitamin B12 serum levels are associated with cognitive decline and mental illness. The chronic use of methamphetamine (MA), which is a highly addictive drug, can induce cognitive impairment and psychopathological symptoms. There are few studies addressing the association of MA with vitamin B12 serum levels. This study examined whether the serum levels of B12 are associated with MA addiction.Methods: Serum vitamin B12, homocysteine (Hcy), glucose and triglyceride concentrations were measured in 123 MA addicts and 108 controls. In addition, data were collected on their age, marital status, level of education and Body Mass Index (BMI) for all participants. In the patient group, the data for each subject were collected using the Fagerstrom Test for Nicotine Dependence (FTND), the Alcohol Use Disorders Identification Test (AUDIT), and a drug use history, which included the age of onset, total duration of MA use, the number of relapses and addiction severity.Results: Our results showed that MA addicts had lower vitamin B12 levels (p < 0.05) than those of healthy controls, but Hcy levels were not significantly different between the two groups (p > 0.05). Serum B12 levels were negatively correlated with the number of relapses in the MA group. Furthermore, binary logistics regression analysis indicated that the B12 was an influencing factor contributing to addiction severity.Conclusion: The findings of this study suggest that some MA addicts might have vitamin B12 deficiency, and serum B12 levels may be involved in the prognosis of MA addiction.

Facial nerve paralysis is a common complication following cerebellopontine angle (CPA) surgery. This study investigated the prognostic value of facial nerve motor-evoked potentials (FNMEPs) elicited by transcranial electrical stimulation for facial nerve outcome after CPA tumorectomy. A total of 95 patients were enrolled in this study between January 2014 and January 2016. All these patients underwent CPA tumorectomy (unilateral, n = 95; bilateral, n = 1). Intraoperative FNMEP elicited by transcranial electrical stimulation was recorded. The short- and long-term postoperative facial nerve functions were evaluated according to the House–Brackmann (HB) scale. The correlation between perioperative changes in the FNMEP stimulus threshold (delta FNMEP = postoperative stimulus threshold level–preoperative stimulus threshold level) and postoperative facial nerve functions were analyzed. On the first day postoperatively, the facial nerve function was HB grade I in 67, grade II in 17, grade III in 7, and grade IV in 5 facial nerves. One year postoperatively, the facial nerve function was grade I in 80, grade II in 11, grade III in 3, and grade IV in 2 facial nerves. The delta FNMEP was significantly correlated with the short- and long-term facial nerve function; receiver operating characteristic (ROC) curves yielded a cut-off delta FNMEP value of 30 V (sensitivity, 91.3%; specificity, 98.6%) and 75 V (sensitivity, 100%; specificity, 98.8%) for predicting short- and long-term facial nerve function damage, respectively. FNMEP elicited by transcranial electrical stimulation is an effective and safe approach for predicting facial nerve function in CPA tumorectomy. A high delta FNMEP is a potential indicator for the prediction of postoperative facial nerve damage.

The hippocampal circuitry is widely recognized as susceptible to ischemic injury and seizure generation. However, hippocampal contribution to acute non-convulsive seizures (NCS) in models involving middle cerebral artery occlusion (MCAO) remains to be determined. To address this, we occluded the middle cerebral artery in adult C57 black mice and monitored electroencephalographic (EEG) discharges from hippocampal and neocortical areas. Electrographic discharges in the absence of convulsive motor behaviors were observed within 90 min following occlusion of the middle cerebral artery. Hippocampal discharges were more robust than corresponding cortical discharges in all seizure events examined, and hippocampal discharges alone or with minimal cortical involvement were also observed in some seizure events. Seizure development was associated with ipsilateral hippocampal injuries as determined by subsequent histological examinations. We also introduced hypoxia-hypoglycemia episodes in mouse brain slices and examined regional hyperexcitable responses ex vivo. Extracellular recordings showed that the hippocampal CA3 region had a greater propensity for exhibiting single/multiunit activities or epileptiform field potentials following hypoxic-hypoglycemic (HH) episodes compared to the CA1, dentate gyrus, entorhinal cortical (EC) or neocortical regions. Whole-cell recordings revealed that CA3 pyramidal neurons exhibited excessive excitatory postsynaptic currents, attenuated inhibitory postsynaptic currents and intermittent or repetitive spikes in response to HH challenge. Together, these observations suggest that hippocampal discharges, possibly as a result of CA3 circuitry hyperexcitability, are a major component of acute NCS in a mouse model of MCAO.

Background: The aim of this study was to evaluate the clinical performance of VersaTrek 528 compared to BACTEC FX 400 blood culture (BC) systems. Materials and Methods: Simulated and clinically obtained BCs were used in the study. Confirmed bacterial species (n = 78), including 43 Gram-positives, 30 Gram-negatives, and 5 Candida albicans strains, were each inoculated into BC bottles. Clinically obtained BCs were subdivided into two groups, A and B. In group A were 72 BC sets (pair: aerobic and anaerobic) in which a set inoculated with 5 ml blood was processed in the VersaTrek BC system, whilst the one inoculated with 10 ml blood was processed in the FX BC system. In group B, 76 BC sets (pairs) corresponding to 152 VersaTrek bottles and 152 FX bottles were inoculated with the same volume (10 ml) of blood, and processed in each system. Results: In the simulated BC study, 90% (63/70) of the VersaTrek aerobic bottles were positive, which was higher than that of FX 400 (59/70, 84%), but was not statistically significant (P = 0.423). In contrast, FX 400 anaerobic bottles had a higher positive rate than the other BC system (84 vs. 77%), although it was statistically insignificant (P = 0.267). Time to detection of organisms in the two BCs was comparable for both aerobic (P = 0.131) and anaerobic bottles (P = 0.104). In clinical BCs of group A, FX BC system had slightly higher positive rates for both aerobic (11.1 vs. 9.7%, P = 0.312) and anaerobic (8.3 vs. 6.9%, P = 0.375) bottles. However, the difference was not statistically significant. In group B, VersaTrek aerobic bottles had a higher positive rate compared to the other BC system (10.5 vs. 5.2%, P = 0.063). In terms of positive rates of sub-studies A and B, VersaTrek and FX BC systems were comparable. Conclusion: There was no significant difference between the two BC systems in the detection of bacteria and fungi in simulated BCs. In clinical BCs, the performance of the VersaTrek BC system, with inoculation of 5 or 10 ml patient’s blood, was comparable to the FX system with inoculation of 10 ml patient’s blood.

The aim of the meta-analysis was to evaluate the association between 10 widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and ankylosing spondylitis (AS).A comprehensive literature search, screening of eligible articles and data extraction was performed independently by two investigators. Further meta-analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX, USA). The association between IL-23R polymorphisms and AS was evaluated by odds ratio (OR) and 95% confidence intervals (95% CI).Twenty-five case-control studies with 8431 cases and 8972 controls were included in this meta-analysis. Quantitative meta-analysis revealed that minor allele frequency (MAF) of rs1004819, rs1495965, and rs2201841 was significantly higher in the AS group (p value .001, .001, = .010, respectively). MAF of rs10489629, rs11209026, rs11465804, and rs1343151was significantly lower in the AS group (p value = .002, .001, = .032, .001, respectively). However, there is no significant difference between these two groups in rs10889677, rs11209032, and rs7517847 frequency (p value = .128, .237, .131, respectively).The present study indicates that minor allele carriers of rs1004819, rs1495965, and rs2201841 are susceptible to AS. Conversely, minor alleles of rs10489629, rs11209026, rs11465804, and rs1343151 have protective effect on AS.

Epilepsy is a common neurological disorder characterized by naturally-occurring spontaneous recurrent seizures and comorbidities. Kindling has long been used to model epileptogenic mechanisms and to assess antiepileptic drugs. In particular, extended kindling can induce spontaneous recurrent seizures without gross brain lesions, as seen clinically. To date, the development of spontaneous recurrent seizures following extended kindling, and the effect of the antiepileptic drugs on these seizures are not well understood. In the present study we aim to develop a mouse model of extended hippocampal kindling for the first time. Once established, we plan to evaluate the effect of three different antiepileptic drugs on the development of the extended-hippocampal-kindled-induced spontaneous recurrent seizures. Male C57 black mice were used for chronic hippocampal stimulations or handling manipulations (twice daily for up to 70 days). Subsequently, animals underwent continuous video/EEG monitoring for seizure detection. Spontaneous recurrent seizures were consistently observed in extended kindled mice but no seizures were detected in the control animals. The aforementioned seizures were generalized events characterized by hippocampal ictal discharges and concurrent motor seizures. Incidence and severity of the seizures was relatively stable while monitored over a few months after termination of the hippocampal stimulation. Three antiepileptic drugs with distinct action mechanisms were tested: phenytoin, lorazepam and levetiracetam. They were applied via intra-peritoneal injections at anticonvulsive doses and their effects on the spontaneous recurrent seizures were analyzed 10–12 h post-injection. Phenytoin (25 mg/kg) and levetiracetam (400 mg/kg) abolished the spontaneous recurrent seizures. Lorazepam (1.5 mg/kg) decreased motor seizure severity but did not reduce the incidence and duration of corresponding hippocampal discharges, implicating its inhibitory effects on seizure spread. No gross brain lesions were observed in a set of extended hippocampal kindled mice submitted to histological evaluation. All these data suggests that our model could be considered as a novel mouse model of extended hippocampal kindling. Some limitations remain to be considered.