Search

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.

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.

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.

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: 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.

// 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.

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 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...

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.

The aim of the present study was to investigate the spontaneous development of growth and weight gain of patients with Prader-Willi syndrome (PWS) in Mainland China. We retrospectively analyzed 120 cases of PWS diagnosed from 1994 to 2014 in Mainland China. Scatter diagram of the growth data was compared to standardized growth curve. The length at birth was similar to the normal population and the mean birthweight is under the 50th centile of normal population. Heights in 43% (27/62) of patients had dropped off below the 3(rd) centile of their peers after 5 years of age. Weights in 65.9% (58/88) of patients had exceeded the 97(th) centile of their peers after 3 years of age. Early obesity is obvious in 92.9% (66/71) of patients with body mass index (BMI) up the 97(th) centile of their peers from 2-3 years of age. Final mean height is 149.3 ± 11.2 cm for females (n = 7) and 146.2 ± 9.8 cm for males (n = 6), showing 11.3 cm and 26.6 cm below the average height for normal Chinese girls and boys. The growth pattern of PWS in Mainland China is comparable to those in Caucasians. Early intervention with recombinant human growth hormone is warranted considering the early onset of growth retardation and obesity.

This study was aimed to investigate the effects of Wenyangbushen formula on the mRNA and protein expression of VEGF, OPG, RANK, and RANKL in the steroid- induced avascular necrosis of the rabbit femoral head (SANFH) and to further explore the potential mechanism of this formula on the treatment of SANFH. One hundred and thirty six New Zealand rabbits were randomly divided into 5 groups (n=24 rabbits in each group): normal group, model group, Traditional Chinese Medicine (TCM) Wenyangbushen decoction at low, moderate and high dose group. The normal group and positive control group were intragastrically (i.g.) administered with saline. The TCM group was treated with Wenyangbushen decoction at the indicated dosage. After treated for eight weeks, the mRNA and protein expression of VEGF, OPG, RANK, and RANKL in the femoral head tissues was determined by RT-PCR and Western blotting, respectively. Wenyangbushen decoction treatment can effectively promote bone cells, osteoblasts and chondrocytes growth, as well as prevent the cell apoptosis in SANFH. The mRNA and protein expression of OPG and VEGF was increased while the levels of RANK and RANKL were reduced in the necrotic tissue of model group compared with those in the normal rabbits. And Wenyangbushen treatment prevented those changes, as manifested by up-regulation of VEGF and OPG, while down-regulation of RANK and RANKL levels in a dose-dependent manner. Wenyangbushen Formula treatment can alleviate necrosis of femoral head induced by steroid. It can promote bone cells, osteoblasts and chondrocytes growth, as well as prevent the cell apoptosis. Meanwhile, it up-regulates OPG and VEGF while inhibits RANK and RANKL expression. This may be one of the mechanisms for the effective treatment of SANFH.

Patients suffer hemispatial neglect after stroke. However, whether the function of spatial attention is reorganized to the contralateral brain remains poorly understood. Here we present a case report of neonatal stroke to demonstrate the reorganization of spatial attention in the contralateral hemisphere using a series of tests including star cancellation task, line bisection test, the bells test, letter cancellation test, and drawing tests. The patient underwent right hemispherectomy for treatment of refractory epilepsy and did not have hemispatial neglect after surgery, supporting transfer of function prior to the operation. After analyzing the literature in this field, we proposed that the function of spatial attention may transfer to the contralateral side in childhood. Thus, this study sheds new light on the preserved function of spatial attention in neonatal stroke patients even when hemispherectomy is performed.

The study aims to analyse the clinical and immunological manifestations of paediatric antiphospholipid syndrome (APS) in patients, based on the 2006 revised classification criteria of definite APS. Fifty-eight paediatric patients with APS were enrolled and analysed retrospectively. A total of 37 female and 21 male patients with a mean age of 14 ± 3 years at disease onset were included. Fourteen (24%) cases were primary APS, and 40 (69%) cases were secondary to systemic lupus erythaematosus (SLE). Anti-nuclear antibody (ANA) positivity and hypocomplementemia were more common in secondary APS than in primary APS. The most common manifestations of thrombosis were deep vein thrombosis of the lower extremities (25 cases, 37%). Non-thrombotic manifestations were mainly immunologic thrombocytopenia, autoimmune haemolytic anaemia, skin lesions, arthritis, pulmonary hypertension, heart valve vegetations and spontaneous abortion. LA, ACL and anti-β2GPI were positive in 42 (95%), 28 (64%) and 34 (77%) cases, respectively. Over half (23 cases, 52%) of the patients were triple-positive for antiphospholipid (aPL) antibodies. Among patients with single-positive LA and anti-β2GPI, the proportion with venous thrombosis was 100% (5 cases) and 0% (0 cases), respectively. The arterial thrombosis proportions were 22% (5 cases), 21% (3 cases) and 14% (1 case) in the triple-, double- and single-aPL-positive groups, respectively (P > 0.05). Fifty-three (91%) cases were followed up for 3 to 140 months, with a median time of 32 months. Seven (13%) cases had recurrences or appearances of thrombosis during follow-up, all of which were double- or triple-aPL positive. APS in the paediatric patients is mostly secondary to SLE. ANA positivity and hypocomplementemia are more common in secondary APS, but there are no differences in the other clinical manifestations between the primary and secondary APS groups. Deep vein thrombosis is the most common thrombotic event. Positive LA may increase the risk of venous thrombosis. Multiple-aPL positivity does not increase the proportion of thrombosis. Long-term anticoagulant or antiplatelet therapy is needed to prevent thrombosis recurrence in double- or triple-positive aPL cases.

Background Glomerular filtration rate (GFR) is essential for renal function evaluation and classification of chronic kidney disease (CKD), while the reference method in children are cumbersome. In the Chinese children, there was no data about GFR measured through plasma or renal clearance of the exogenous markers, and therefore no validated GFR-estimating tools in this population. Methods We measured GFR with double-sample plasma clearance of 99mTc-DTPA (mGFR) in 87 hospitalized children with renal injury. Using mGFR as the golden standard, we evaluate the efficiency of four different GFR estimation equations (the original and update Schwartz equation, the Filler equation, the CKiD equation) by statistical parameters of correlation, precision and accuracy. Results In our population, mGFR was 97.0± 31.9 mL/min/1.73m2. The updated Schwartz equation, the Filler equation and the CKiD equation, produced eGFR with strong correlation with mGFR, strong explanation capacity of variance in mGFR, small bias, satisfactory performance in Bland-Altman analysis, high intra-class correlation coefficients, high ratio of eGFR within mGFR±10% and eGFR within mGFR±30%, good agreement in CKD staging between eGFR and mGFR. The original Schwartz equation produced eGFR with large bias, poor precision and accuracy. Conclusion The validated equations to estimate GFR in our patients are the updated Schwartz equation, which is simple for bedside use, the Filler equation and the CKiD equation, which provide more accurate eGFR. The original Schwartz equation should not be applied to estimate GFR in Chinese children with kidney injuries.

Introduction Benzodiazepine GABA enhancers and levetiracetam are known to be effective in suppression of kindling seizures, but the effects of these antiepileptic drugs on regional after discharges adjacent to the kindling sits are largely unknown. We explored this issue in a mouse model of hippocampal kindling and compared the effects of lorazepam and levetiracetam on hippocampal and piriform after discharges as the piriform cortex is thought to play a critical role in genesis of kindling seizures. Methods C57 black mice received electrode implantations in unilateral hippocampal CA3 and piriform cortical areas and then underwent twice daily hippocampal stimulation for a few weeks. The effects of antiepileptic drugs were tested in fully kindled mice. Lorazepam (1.5 mg/kg) or levetiracetam (100 mg/kg) was applied by an intra-peritoneal injection 15 or 60 min before hippocampal stimulation. The effects observed following similar saline injections were taken as baseline controls. Results Evoked motor seizures and associated piriform after discharges were abolished by lorazepam whereas the durations of corresponding hippocampal afterdischarges were unchanged from baseline controls (n = 6 mice). Evoked motor seizures and corresponding hippocampal and piriform afterdischarges were significantly decreased by levetiracetam, but shortened afterdischarges were more pronounced in the piriform than in the hippocampal area (n = 6 mice). Summary Lorazepam may suppress motor seizures by inhibiting seizure spread from the stimulated hippocampal focus to the piriform cortex and other brain areas, and levetiracetam may inhibit both focal/hippocampal seizures and seizure spread in our model.

Chronic subdural hematoma (CSDH) is an inflammatory and angiogenic disease. Vascular endothelial growth factor (VEGF) has an important effect on the pathological progression of CSDH. The matrix metalloproteinases (MMPs) and VEGF also play a significant role in pathological angiogenesis. Our research was to investigate the level of MMPs and VEGF in serum and hematoma fluid. Magnetic Resonance Imaging (MRI) shows the characteristics of different stages of CSDH. We also analyzed the relationship between the level of VEGF in subdural hematoma fluid and the appearances of the patients' MRI. We performed a study comparing serum and hematoma fluid in 37 consecutive patients with primary CSDHs using enzyme-linked immunosorbent assay (ELISA). MMP-2 and MMP-9 activity was assayed by the gelatin zymography method. The patients were divided into five groups according to the appearance of the hematomas on MRI: group 1 (T1-weighted low, T2-weighted low, n=4), group 2 (T1-weighted high, T2-weighted low, n=11), group 3 (T1-weighted mixed, T2-weighted mixed, n=9), group 4 (T1-weighted high, T2-weighted high, n=5), and group 5 (T1-weighted low, T2-weighted high, n=8). Neurological status was assessed by Markwalder score on admission and at follow-up. The mean age, sex, and Markwalder score were not significantly different among groups. The mean concentration of VEGF, MMP-2, and MMP-9 were significantly higher in hematoma fluid than in serum (p

UNLABELLED Fat hypertrophy, intravascular coagulation, and fat emboli are important risk factors of steroid-induced ischemic bone necrosis (SI-IBN) which may develop during the initial one year after commencing the use of steroids. This pathology is best studied by MRI, particularly for its staging. The cautious strategies such as low dose, oral route, short duration of steroid usage, use of steroid sparing agent, and alcohol avoidance should be followed as a traditional therapy. The objective of this review article was to recognize and evaluate various Treatment strategies for steroid-induced ischemic bone necrosis of femoral head. LITERATURE SEARCH Various electronic databases including PubMed, Google and Cochrane library were comprehensively searched for articles on steroid-induced ischemic bone necrosis of femoral head and its treatment strategies. Ninety four articles were reviewed, examined and importantly appraised and the most appropriate 32 papers were used to write this review article. CONCLUSION Bisphosphonates, alendronate, and hyperbaric oxygen (HBO) treatments have been reported to be effective against IBN. To recommend the regular use of bisphosphonate in IBN patients, more evidences with a larger number of patients are required to verify its therapeutic effectiveness. Core decompression, osteotomy, bone graft and tantalum rod are the surgical approaches for the management of IBN. Advance form of IBN (bone tissue collapse) is advised to be treated with arthroplasty which should be durable, particularly in young patients.

Objective The aim of the current study was to determine the contributions of several common mutations in the Mediterranean fever (MEFV) gene, namely, E148Q, M680I, M694V and V726A, to ankylosing spondylitis (AS) susceptibility. Methods Two investigators independently searched the literature regarding the association of MEFV with AS in the PubMed, EMBASE, Web of Science, and Scopus databases. They independently selected eligible articles and then extracted data from the included studies. The associations between MEFV mutations and AS risk were assessed with odds ratios (ORs) and 95% confidence intervals (95% CI). Further analyses were conducted with STATA 12.0 software (Stata Corp.; College Station, Texas, USA). Results Four mutations (E148Q, M680I, M694V and V726A) were genotyped in 869 AS cases and 879 controls from the 8 eligible studies. Of the four mutations, M694V (pooled OR: 3.330, 95% CI: 2.129–5.208) was found to be associated with AS through overall analysis. However, the other mutations demonstrated no relation with AS (pooled ORs: 1.295, 1.258, 1.778; 95% CI: 0.886–1.891, 0.688–2.298 and 0.938–3.371). No significant publication bias was discovered in the meta-analysis. Conclusions The present study indicates that the MEFV M694V mutation may contribute to the pathogenesis of AS. The associations between the other mutations and AS need to be validated with more relevant and well-designed studies.

Background:Multidetector computed tomography (MDCT) exhibited wide ranges of sensitivities and specificities for lymph node assessment of gastric cancer (GC) in several individual studies. This present meta-analysis was carried out to evaluate the value of MDCT in diagnosis of preoperative l

Elevated levels of acute-phase proteins, a systemic marker for inflammation, predict coronary events; Chlamydia pneumoniae (C. pneumoniae) infection is associated with coronary atherosclerosis. The present study investigated whether inflammation or infection is involved in the pathogenesis of acute coronary syndrome (ACS) and which one has the more important role. The study group comprised 49 patients with angiographically diagnosed ACS, 48 cases of chronic coronary heart disease (CCHD), and 44 subjects with a normal coronary profile. The levels of serum C-reactive protein (CRP), fibrinogen and anti-C. pneumoniae IgG antibody were measured. The IgG antibody against C. pneumoniae was higher in the ACS and CCHD groups compared with the control group after adjusting for age and gender. The levels of CRP and fibrinogen were significantly increased in patients with ACS compared with controls and CCHD patients. Multiple stepwise logistic regression analysis revealed that C. pneumoniae IgG antibody is an independent risk factor for both ACS and CCHD (odds ratio 2.3 and 2.1, respectively), but the CRP level is a risk factor only for ACS (odds ratio 6.9). The inflammatory response, as indicated by acute-phase proteins, especially CRP, rather than C. pneumoniae infection, may contribute more to the clinical course of ACS.

The present study was performed to determine quantitatively the effect of hypercholesterolemia induced by a lipid-rich diet on glomerulosclerosis in an animal model of nephrotic syndrome (NS) induced by Adriamycin (ADR). Twenty NS Wistar rats administered ADR with a single intravenous dose of 5 mg/kg body weight were divided into standard and lipid-rich chow groups. Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as controls. Quantitative analyses of renal histological changes were performed with determination of blood and urine biochemical parameters. It was found that serum cholesterol was markedly higher in rats with lipid-rich chow in both NS and non-NS rats. Urinary protein was significantly higher in rats on the lipid-rich diet in the NS group. The mesangial matrix and cell indices were significantly increased in rats with the lipid-rich diet and the most obvious changes were found in the NS group. Lipid deposits and foam cells were observed in mesangial areas, and some glomeruli had progressed to form focal and segmental glomerulosclerosis in the NS group. Findings indicated that diet-induced hyperlipidemia can lead to proliferation of mesangial cells and accumulation of mesangial matrices, and further aggravate glomerulosclerosis in Adriamycin-induced nephrosis.