Objective To investigate the clinical characteristics, imaging features and treatment strategies of pial arteriovenous fistula. Methods From January 2013 to December 2017,12 patients with pial arteriovenous fistula confirmed by cerebral angiography and received treatment at the Department of Neurosurgery,Xuanwu Hospital, Capital Medical University were retrospectively recruited. All patients underwent endovascular embolization with Glubran 2,coil + Glubran 2 or Onyx 18. Some patients underwent balloon-assisted embolization. The embolization effect (complete occlusion,subtotal occlusion,partial occlusion) and postoperative complications were observed. Patients were followed up to evaluate symptom relief and radiological outcomes (previous lesions not visualized by re-examination imaging). Results For the initial symptoms,there were 6 headaches, 3 seizures,2 intracranial hemorrhages, and 1 tinnitus. After embolization, 11 patients had complete occlusion of the fistula and One patient had subtotal occlusion. Six patients underwent balloon-assisted embolization. One patient developed a decrease in muscle strength in the left limb after embolization. There were no deaths. Eleven patients completed the followup. The median follow-up time was 13. 4 (5. 2,26. 7) months. Nine patients had symptoms disappeared. One patient still had headache and 1 patient received oral antiepileptic drugs to control seizures. The fistulas were not visualized by angiopathy in all 11 patients. One patient developed dural arteriovenous fistula and arteriovenous malformation in superior sagittal sinus, straight sinus and sinus confluence. The patient was cured by embolization. Conclusions Pial arteriovenous fistula is a rare clinical disease, which is often characterized by headache, seizure, etc. Endovascular therapy is a safe and effective treatment method.

Objective To investigate the clinical manifestations,radiographic presentations,histopathological features,treatment and clinical follow-up of IgG4 related disease (IgG4-RD).Methods Forty-nine cases in our hospital were enrolled from 2009 to 2012 and were followed up.Results Of the 49 patients with IgG4-RD,the male to female ratio was 2.1∶1,the mean age was (53±15) years,and the serum IgG4 ranged between 0.39 to 20.8 g/L.The most commonly affected organ was pancreas.Two or more organs were involved in 15 patients.Histopathological findings included tissue infiltration by lymphocytes,IgG+ plasma cells and IgG4+ plasma cells and diffuse fibrosis among 45 patients.The IgG4+ plasma cells were over 10/high power fields (HPF).Responses to glucocorticoid in combination with immunosuppressants were good except 3 patients suffered relapses.Conclusion IgG4-RD is an autoimmune disease affecting multiple organs,and the increased IgG4 positive plasma cells is characteristic.This disease can be effectively alleviated with prompt use of glucocorticoid.

Objective:To investigate the effect and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomal microRNA-1297 (miR-1297) on hippocampal neuron damage in depressed rats.Methods:BMSCs and BMSCs-derived exosomes were prepared and identified. Rats were first injected with corticosterone to establish the model of depression, and then injected with BMSCs-derived exosomes. Superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), TNF-α and IL-1β in rat serum samples, hippocampal tissues and neurons were detected. Expression of miR-1297 in hippocampal tissues and neurons was detected by RT-qPCR. A rat hippocampal neuron injury model was established to investigate the role of BMSC-derived exosomes and miR-1297 in neuronal apoptosis and proliferation. The targeting relationship between miR-1297 and connective tissue growth factor (CTGF) was analyzed using dual luciferase reporter genes.Results:In the hippocampus of depressed rats, the expression of miR-1297 was low, while the expression of CTGF was elevated. Exosomes derived from BMSCs can inhibit the expression of CTGF by up-regulating the level of miR-1297, thereby inhibiting neuronal cell apoptosis in the hippocampus of depressed rats, while increasing the level of SOD, and reducing inflammatory damage, and ultimately improving the behavioral function of depressed rats.Conclusions:Depressed rats showed decreased expression of miR-1297 and increased expression of CTGF. BMSC-derived exosomes inhibited CTGF expression through up-regulating miR-1297, thereby improving hippocampal neuron damage in rats with depression.

Objective:To summarize the characteristics and treatment outcomes of immunoglobulin G4-related disease (IgG4-RD) overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods:The clinical data of four patients with AAV overlaped with IgG4-RD from Zhongshan Hospital of Fudan University from August 2018 to July 2019 were collected and the related literature were reviewed.Results:Four patients were included, in which two were diagnosed with IgG-RD and granulomatosis with polyangiitis (GPA), one was probable IgG4-RD and microscopic polyangiitis (MPA), and one was probable IgG4-RD and GPA. All patients were female, with an average age of (42±12) (26-56) years, and disease duration was (7±4) (4-13) months. The manifestations were ocular inflammatory pseudotumor, sinusitis, otitis media, mastoiditis, parotitis, meningitis, lung and kidney involvement. After treatment with glucocorticoid and immunosuppressants (including cyclophosphamide, methotrexate, azathioprine, leflunomide), 2 patients failed to achieve remission, and 2 patients relapsed 8-15 months after treatment. One patient was treated withglucocorticoid pulse therapy combined with rituximab and one was treated with glucocorticoid combined with methotrexate and rituximab, and the patient was relieved.Conclusion:AAV and IgG4-RD may be a new overlap syndrome. Hypertrophic meningitis, orbital mass, chronic periaortic inflammation and interstitial glomerulonephritis are reported in the literature. The pathological changes of orbit, nasopharynx, parotid gland and lung are common. Glucocorticoids and immunosuppressive agents have poor treatment response, which indicates that AAV is refractory when combined with elevated IgG4. The induced remission rate is low, and easy to relapse. Glucocorticoid pulse therapy and rituximab treatment are effective.

Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.

Objective To evaluate the performance of Positron emision tomography (PET) in the assessment of disease activity of Takayasu arteritis (TA). Methods Information retrieval was based on database such as PubMed/Medline and CNKI, etc. The research before Dec 2016 involving Takayasu arteritis and PET were included.The quality of the research was evaluated by diagnostic accuracy studies-2Q(UADAS-2) and the data was analyzed by Meta-disc. Results Among the 70 research, nine studies were included in this study with a total of 126 patients and 254 controls. All patients were diagnosed according to the classification criteria of American College of Rheumatology. The disease activity was mostly assessed by the scoring system of National Institutes of Health and by clinical assessment in one study. The result of PET was evaluated by visual grade and semi-quantitative analysis. The pooled DOR of the 9 studies was 17.54, the pooled sensitivity and specificity was 84% and 73%,respectively.However,the heterogeneity of specificity was 81.4%. Two studies had included one patients repeatedly and suspected active patients were included in the in-active group in one study,which might impact the statistical result of the meta-analysis.After excluded these studies, the pooled DOR was 30.32. The pooled sensitivity and specificity was 86% and 85%, respectively, with better consistency. Conclusion PET shows stable sensitivity and variant specificity in the diagnosis and assess of disease activity of TA, which is a useful method in the clinically evaluation of disease activity of TA.

Objective:To analyze the characteristics of patients with Takayasu arteritis (TA) in the east China Takayasu arteritis (ECTA) cohort and their subgroups, and evaluate the disease characteristics.Methods:Patients diagnosed with TA in ECTA cohort from January 2009 to October 2019 were enrolled and their data were analyzed. The characteristics were analyzed and compared within subgroups using t-test or Wilcoxon rank sum test or Chi-square test. Results:A total of 454 patients were included, with the male to female ratio of 1∶4.75(79/375), and the main complaint were dizziness/headache, fatigue, and chest tightness/pain. The type Ⅴ and Ⅰ were the most common angiographic pattern, among which the subclavian artery and carotid artery were most vulnerable, manifested as vascular stenosis. Hypertension, tuberculosis and hepatitis B were common complications. In subgroup comparison, symptoms and inflammation index were much more evident in the active group, female group, <40 years old, and newly diagnosed group. C-reactive protein (CRP)[10(2, 33) mg/L vs 3(1, 14) mg/L, Z=-4.49, P<0.01), erythrocyte sedimentation rate (ESR) [(45±33) mm/1 h vs (25±23) mm/1 h, t=-5.82, P<0.01), in the active group were significantly higher than those in the inactive group, while the ESR in female patients was only higher than that in males, but without statistical significant difference. SAA in the young age group, ESR in the newly diagnosed group was significantly higher than that in the other subgroups [19(6, 95) mg/L vs 10(4, 39) mg/L, Z=2.06, P<0.05] [(44±34) mm/1 h vs (32±28) mm/1 h, t=3.77, P<0.01]. Conclusion:The TA patients are mainly young women, and are in active disease when first being diagnosed. The type Ⅴ and Ⅰ are the most common artery involve-ment pattern. Hypertension and tuberculosis are the most frequent complications.

Objective:To investigate the effect of lenalidomide (LEN) combined with temozolomide (TMZ) on proliferation, invasion, drug resistance and O6-methylguanine-DNA methyltransferase ( MGMT) gene epigenetic modification of TMZ-resistant human glioblastoma cell line U251/TR. Methods:A TMZ-resistant human glioma cell line, U251/TR, was successfully established by stepwise exposure of U251 parental cells to TMZ. U251/TR cells were divided into dimethyl sulfoxide (DMSO) group, LEN group, TMZ group and LEN+TMZ group (DMSO group: without any drug intervention; LEN group, TMZ group, and LEN+TMZ group were pretreated with 100 μmol/L LEN, 200 μmol/L TMZ, 100 μmol/L LEN+200 μmol/L TMZ, respectively; the drugs were administered once every 24 h). The proliferation rate of these cells in each group was detected by sulfonylrhodamine B colorimetric assay at different time points (24, 48, 72, and 96 h after treatment). At 96 h after treatment, the invasion and migration abilities of cells in each group were detected by Transwell assay; the proliferation cycle of cells in each group was detected by flow cytometry; Western blotting, immunohistochemical staining and immunofluorescence staining were used to detect the MGMT protein expression, and the MGMT mRNA expression in cells of each group was detected by reverse transcription-PCR; methylation specific PCR was used to detect the MGMT gene promoter methylation in each group of cells. Results:The cell proliferation rate of LEN+TMZ group was significantly decreased as compared with TMZ, LEN, and DMSO groups at 24, 48, 72 and 96 h after treatment ( P<0.05). At 96 h after treatment, LEN+TMZ group had significantly decreased number of transmembrane cells, and significantly increased ratio of cells at G0/G1 phase as compared with the other 3 groups ( P<0.05); the MGMT protein and mRNA expression levels in TMZ group and LEN+TMZ group were significantly lower than those in LEN group and DMSO group ( P<0.05); and the number of cells with strong or moderate MGMT expression in TMZ group and LEN+TMZ group was obviously less than that in LEN group and DMSO group, and the MGMT fluorescence intensity in TMZ group and LEN+TMZ group (+) was obviously lower than that in LEN group (+++) and DMSO group (+++). The MGMT gene promoter was unmethylated in all groups. Conclusion:LEN alone does not obviously inhibit the proliferation and invasion of U251/TR cells; but LEN combined with TMZ could inhibit the proliferation and invasion of U251/TR cells and co-reverse the drug resistance of U251/TR cells, whose mechanism is not related to the changes of MGMT gene promoter methylation.