Objective To study the effect of dimethyl fumarate (DMF) on Aβ-induced oxidative stress by regulating NF-E2-related factor 2 (Nrf2) expression and its mechanism.Methods Rat astrocytes were divided into Aβ group,DMF group,Nrf2 group and Nrf2 +DMF group.Expressions of Nrf2,Nqo1,Ho-1,Keap1 mRNA and HDAC were detected by RT-PCR and Western blot respectively.Results The expression levels of Nrf2,Nqo1 and HO-1 mRNA were significantly lower in Nrf2 group and Nrf2+DMF group than in Aβ group and DMF group (P＜0.05) and were significantly higher in DMF group than in Aβ group (P＜0.05) while the expression level of Keap1 mRNA was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (P＜0.05).The expression level of HDAC was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (6.41±0.43 vs 9.01±1.54,P＜0.05;6.72±0.30 vs 8.76± 0.74,P＜0.05).Conclusion DMF increases the Nrf2 expression by inhibiting the HDAC expression,thus reducing Aβ-induced oxidative stress in rat astrocytes.

Objective To explore the clinical features of patients with vertebrobasilar dolichoectasia (VBD).Methods Patients diagnosed with posterior circulation ischemia in our hospital from October 2008 to January 2012 were consecutively collected and were divided into the VBD group and the non-VBD (NVBD) group.Clinical manifestations,risk factors,hemodynamic parameters and neuroimaging features were collected.Results (1) Statistical difference was observed in dyslipidemia,hypertension and the history of diabetes in the two groups (P ＜ 0.05).(2) The cerebral hemodynamic features of the VBD patients were as the following:decreased peak systolic velocity of vertebral artery and basilar artery and decreased systolic/diastolic ratio.Statistical difference was showed in the average peak flow velocity(Vm),pulsatility index(PI) and resistance index(RI) (P =0.036,0.032,0.032,respectively).(3) The main clinical manifestations of VBD were ischemic cerebrovascular disease,hemorrhagic cerebrovascular disease,oppression,brain damage symptoms and hydrocephalus.(4) The diagnosis in most of the VBD patients was confirmed by neural imaging and MRI was the first choice.Conclusion The VBD patients have relative unique clinical features.MRI should be the first choice for neuroimaging.

Objective:To investigate the protective effect of rifampicin in a rat model of global cerebral ischemia /reperfusion ( GCIR) and discuss the influence of rifampicin on microglial activation.Methods:The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and systemic hypotension.Forty-two male SD (Sprague-Dawley) rats were randomly assigned to three groups:sham group ,I/R and I/R+FRP treated group.The rats in I/R+RFP group were treated with rifampicin 20 mg/kg by intra-peritoneal injection 30 min after reperfusion , while the other groups were treated with normal saline.Morris water maze test was performed for neurobehavioral test ,HE staining was detected for pathomorphology changes of neurons in CA 1 region.Microglia was im-munohistochemically stained in CA 1 region using ionized calcium adaptive molecular 1 ( IBA-1) as the marker.The protein levels of IL-1β,IL-6 and TNF-αin the hippocampal tissues of rats were also measured by enzyme-linked immunosorbent assay.Results:Rifampin improved the behavior ,shorten the escape latency of rats following GCIR obviously ( P<0.05 ) and reduced the neuron damage in hipp-ocampal CA1 region of rats after GCIR (P<0.05).Additionally,in I/R+FRP treated group the activation of microglia also showed a significantly inhibited compared with I/R group(P<0.05).Futhermore,we also found the expression of IL-1β,IL-6 and TNF-αin hipp-ocampal reduced obviously in I/R+FRP group ( P<0.05 ).Conclusion: Rifampin have obvious protective effect in the rat model of GCIR.The underlying mechanism may be associated with inhibition the activation of microglia ,reduction the expression of IL-1β,IL-6 and TNF-αand suppression the inflammatory response finally.

Aim To investigate the effects of baicalin on cognitive function in global cerebral ischemia reper-fusion rats, and the probable mechanism involved. Methods Sixty male Sprague-Dawley(SD) rats were randomly divided into Sham operation group ( S group) , global cerebral ischemia reperfusion group ( I/R group) , global cerebral ischemia reperfusion + ba-icalin treatment group ( I/RB group) , twenty in each. Model was induced via the bilateral occlusion of the
common carotid arteries plus hemorrhagic hypotension. 12 h after reperfusion, rats in I/RB group were given baicalin (100 mg·kg-1 ) saline solution by intragas-tric administration twice per day for 7 days. Rats in S group and I/R group were given the corresponding dose of saline infusion at the same time. Morris water maze test was employed to detect spatial learning and memo-ry. BrdU immunohistochemistry was used to detect the proliferation of neural precursor cells ( NPCs ) in the
brain. Expression of COX-2 in the brain tissue was measured by Western blot. Results Compared to I/R group, baicalin improved spatial learning and memory damage ( P <0. 05 ) , increased the number of BrdU-positive cells in the DG and SVZ ( P<0. 01 ) , and re-duced the expression of COX-2 in the brain ( P <0. 01 ) . Conclusions Baicalin could ameliorate cog-
nitive function in the rats with global cerebral ischemia reperfusion, which might be associated with its inhibi-tory effects on the expression of COX-2 , thereby in-creasing the proliferation of NPCs in the brain.

Objective:To study the curative efficacy of wenxin granule combined with propafenone in the treatment of arrhythmia and its effects on the serum levels ofhs-CRP,TNF-α,IL-6 and heart function.Methods:96 patients of arrhythmia who were treated from July 2014 to October 2016 in our hospital were selected and randomly divided into the observation group (n=48) and the control group (n=48).The control group was treated with propafenone,while the observation group was treated with wenxin granuleon.Then the serum levels of hs-CRP,TNF-α and IL-6,heart function,clinical efficacy and incidence of adverse reactions were observed and compared between the two groups before and after the treatment.Results:After treatment,the total effective rate of observation group was significantly higher than that of the control group (P＜0.05).The serum levels of hs-CRP,TNF-α and IL-6 of observation group were significantly lower than those of the control group (P＜0.05);the left ventricular end diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD) of observation group were significantly lower than those of the control group,and the left ventricular ejection fraction (LVEF) was significantly higher than that of control group(P＜0.05);the incidence of adverse reactions in the observation group was significantly lower than that of the control group (P＜0.05).Conclusion:Wenxin granule combined with propafenone was effective for arrhythmia,it could effectively improve the heart function and high safety,which might be related to the decrease of serum hs-CRP,TNF-and IL-6 levels.

Objective To investigate the neuroprotective effect of escitalopram on focal cerebral ischemia/reperfusion in rats and its possible mechanisms.Methods Seventy-five male Sprague-Dawley rats were randomly divided into three groups:sham operation,saline control and escitalopram intervention groups (n =25 in each group).A focal cerebral ischemia reperfusion model in rats was induced by the intraluminal suture method.The modified neurological severity scale was used to evaluate neurological deficit in rats (n =5 in each group).Laser confocal technology was used to observe the microvascular diameter,density,and total area in ischemic region (n =5 in each group).Enzyme-linked immunosorbent assay was used to detect the plasma concentration of vascular endothelial growth factor (VEGF) (n =5 in each group).Immunohistochemical staining (n =5 in each group) and Western blotting (n =5 in each group) were used to detect the expression of VEGF in the ischemic brain tissue.Results At day 14 after modeling,the neurological deficit improved more significantly in the escitalopram intervention group than that in the saline control group (4.39 ±0.92 vs.6.57 ± 1.13; P =0.015).The 3D confocal vascular imaging showed that capillary diameter in the escitalopram intervention group was significantly smaller than that in the saline control group (2.93 ± 0.19 μm vs.3.56 ± 0.22 μm; P ＜0.01); the vascular density was significantly higher than that in the saline control group (232.68 ±12.54/0.002 mm3 vs.176.26 ± 10.87/0.002 mm3; P=0.000); the total microvascular area was significantly greater than that in the saline control group (89 154± 3 298 μm2/0.002 mm3 vs.75 368.14± 3 519 μm2/0.002 mm3; P=0.000).Enzyme-linked immunosorbent assay showed that the plasma VEGF concentration in the escitalopram intervention group was significantly higher than that in the saline control group (50.35 ± 5.44 pg/ml vs.13.75 ± 4.12 pg/ml; P =0.000).Immunohistochemical analysis showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was significantly higher than that in the saline control group (P =0.000).Western blotting showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was significantly higher than that in the saline control group (0.94 ±0.18 vs.0.62 ±0.22; P =0.006).Conclusions Escitalopram may reduce neurological deficit in cerebral ischemia/reperfusion in rats.Its mechanisms may be associated with VEGF-mediated angiogenesis.

Objective:To analyze the clinical features and genetic factors of neonatal 17β-hydroxysteroid dehydrogenase type10 (HSD10) deficiency.Methods:The clinical characteristics and genetic test results of a child with HSD10 deficiency coming from Children′s Hospital of Nanjing Medical University in April 2019 were retrospectively analyzed.The keywords" 17β-hydroxysteroid dehydrogenase type 10 deficiency" or " 2-Methyl3-Hydroxybutyryl-CoA dehydrogenase deficiency" or " HSD10" , etc.were searched in various databases, including CNKI, Wanfang, Weipu, Embase and PubMed to review the cases collected from all published data until May 31, 2020.Results:The patient was a newborn male who developed symptoms on the first day after birth.The main signs were metabolic acidosis, increased blood ammonia and lactate, and hypotonia.Trio whole exom sequencing in the patient and his parents identified hemizygous NM001037811: c.650G>A, p.R217Q in the HSD17B10 gene that is inherited from the mother.Since the child died on the third day after birth, no further central nervous system examination was performed.The mother of the child has intellectual disability, the sibling sister is normal and the HSD17B10 locus is wild type.By lite-rature reviewing, 5 newborn cases with clear medical records and genetic test results were listed.All patients were male, and had onset of HSD10 deficiency within 1 week after birth.The main phenotypes include metabolic acidosis (increased blood ammonia and lactate), hypoglycemia, hypotonia, and convulsions.All 6 children died in early infancy.The corresponsive HSD17B10 variants were c. 740A>G/p.N247S, c.677G>A/p.R226Q, c.257A>G/p.D86G and c. 650G>A/p.R217Q, which did not indicate the hot spots of mutation. Conclusions:HSD10 deficiency in the neonatal period is relatively rare.The clinical diagnosis is difficult due to the serious condition and short course of the disease.Severe metabolic acidosis, hypotonia, and convulsions in neonatal patients are the main reasons for the poor prognosis, which can be attributed to the hemizygous variation and heterogeneity of the mutation site in male patients.c.650G>A may be closely associated with severe neonatal HSD10 deficiency, but the molecular biological mechanism needs to be further clarified.HSD10 deficiency has a poor prognosis and lacks effective treatment.

Objective To analyze the clinical,radiological and pathological features of primary leiomyosarcoma of bone and to im-prove the diagnostic level.Methods Totally 6 cases of PLB proved by pathology were collected in our study.The clinical,radiologi-cal and pathological findings were retrospectively analyzed,and combined with the relevant literature to have a comprehensive analy-sis.Results The lesions of 6 patients were solitary,located in femoral (1 case),distal femur (1 case),proximal tibia (2 cases),is-chium (1 case)and humerus (1 case).There was no periosteal reaction in all 6 cases but they all had soft tissue mass,sometimes there may have some mineralization within the tumor.Ill-defined osteolytic bone destruction was detected in 5 patients,while expan-sion of cystic bone destruction was found in the other 1 patients.3 cases had hardened edge,2 cases with adjacent bone cortical thickening.The MR imaging in 5 patients showed iso-intensity signal on T1 WI,a slightly inhomogeneously higher signal on T2 WI and a significant heterogeneously enhancement after injected of Gd-DTPA.Another 1 patient showed a double ring sign,the central area onT1 WI and T2 WI expressed heterogeneous slightly higher signal,the peripheral annular zone was iso-intensity on T1 WI and slightly higher on T2 WI,after injected contrast medium,it was inhomogeneous enhancement.In immunohistochemically,all tumors reacted positively with SMA,3 patients with Desmin and Vimentin positive,2 patients with Ki-67 positive,and there had some scat-tered cells with CD68 positive,but the S-100 were all negative.Conclusion The clinical,radiological and conventional histological manifestations of PLB are not specific.Immunohistochemical and/or ultrastructural analysis who displayed smooth muscle differenti-ation can confirm the diagnosis.

We investigated the roles of the crude antigen(CA) of Clonorchis sinensis and excretory secretory products (ESPs) in the polarization of Th1 and Th2 cells.Bone marrow-derived cells were generated from BALB/c mice and isolated into immature DCs;immature DCs were then treated with either CA (CA stimulated group),ESPs (ESPs stimulated group),LPS (positive control group) or PBS (negative control group) for 24 hours.Then the CD4+T cells were isolated from mouse spleen by using anti mouse-CD4 Microbeads,and further cocultured with stimulated DCs for another 72 hours.The purities of DCs and CD4+ T cells were evaluated by flow cytometry and the expressing levels of T-bet mRNA and GATA-3 mRNA were detected by real-time PCR.ELISA was used to detect the levels of IFN-γ and IL-4 cytokines in the supernatant.mRNA levels of T-bet and GATA-3 in the ESPs group were higher than those in PBS-stimulated group (P＜0.05).The concentrations of IFN-γ and IL-4 cytokines in the culture were increased in the ESPs group,compared with PBS stimulated group(P＜0.05).IFN-γ but not IL-4 was increased in CA group (P＜0.05).The results implied that CA might play a role in Th1 type immune response,and ESPs likely play roles in both Th1 and Th2 immune responses.

Objective To evaluate the accuracy of preoperative MRI in the diagnosis of malformations associated with MRKH syndrome and identification of uterine endometrium to optimize the clinical management.Methods 1 8 females with primary amenor-rhea were studied with MRI performed with a 1.5T or 3.0T imager.All patients were examined in the supine position using a phased-array coil and underwent pelvic MRI.Two experienced radiologists evaluated all the examinations in consensus to assess the pres-ence,position and morphology of vagina,uterus,ovaries and any pelvic abnormalities.Results One or two rudimentary uteri were identified in 17 patients (94.4%).A total of 16 patients (88.9%)had bilateral rudimentary uteri,1 (5.6%)had unilateral rudimentary uteri(it was left sided).1 (5.6%)had no uterine remnants.4 (12.1%)of 33 uterine buds in 4 patients showed differentiation of the center of the uterus into three layer.Bilateral ovaries were present in 1 7 patients,and their shapes,sizes and signals are normal.The vagina and cervix were absent in all cases.Conclusion MRI is a useful diagnostic tool in the preoperative evaluation of MRKH syndrome and the endometrium to further optimize the treatment plan.