Objective To investigate the mechanism of hearing loss caused by tympanic membrane(TM)per-foration.Methods We constructed a full ear finite element model,and the personalized finite element model of TM perforation was constructed to simulate hearing loss caused by TM perforation.The difference between the displace-ment response of the basement membrane and the baseline was applied to simulate hearing loss,and the contribution of various components of the middle ear to hearing loss was analyzed to study the mechanism of hearing loss caused by TM perforation.Results If the coupling of the round window membrane and the middle ear air was removed,the hearing loss at the low frequency was about 40 dB,while the high-frequency was the same as the baseline.Re-moval of the coupling between the inner side of the eardrum and the middle ear cavity resulted in a reduction in par-tial low-frequency hearing and an increase in high-frequency hearing loss.The continuous disconnection between the air in the external auditory canal and the air in the middle ear cavity increased the low-frequency hearing loss.How-ever,after the removal of the coupling between the round window membrane and the middle ear air and the connec-tion between the middle ear air and the lateral side of the TM,the original hearing loss of 40 dB at low-frequency dropped to 10 dB.While the removal of the coupling between the middle ear cavity air and the ossicular chain had no significant impact on hearing loss.Conclusion TM perforation may cause hearing loss by both the reduction of sound transmission and the reduction of sound pressure difference between the two sides of TM.The round window membrane can counteract the influence of the hearing loss caused by TM perforation.

Objective To investigate the efficacy and safety of maintenance treatment with low-dose decitabine after allogeneic stem cell transplantation (allo-HSCT) for high-risk acute lymphoblastic leukemia (ALL). Methods The data of 10 patients with high-risk ALL who received maintenance therapy with low-dose decitabine after allo-HSCT in the First Affiliated Hospital of Zhengzhou University from July 2016 to March 2018 was collected. The incidence of post-transplant relapse and graft-versus-host disease (GVHD) and the safety of the treatment protocol were analyzed. The cumulative incidence of relapse (CIR) rate, disease-free survival (DFS) rate and overall survival (OS) rate were estimated by Kaplan-Meier method. Results Two patients relapsed and the median relapse time of these 10 patients was 575 days after transplantation. The 1-year CIR, OS and DSF rates were 16.7%, 100.0% and 83.3%, respectively. At the end of follow-up, the DFS time after transplantation of 2 patients with p53 mutation were 23 months and 11 months, respectively. There was no induction or alleviation of GVHD caused by decitabine treatment. Nine patients developed grade Ⅰ-Ⅱmyelosuppression. Three patients had unexplained thrombocytopenia after transplantation and their platelet counts recovered after decitabine treatment. Conclusion Maintenance therapy with low-dose decitabine has low hematologic toxicity without increasing GVHD, which could be a maintenance treatment option to prevent relapse after transplantation for patients with high-risk ALL.

Objective To observe the efficacy of maintenance treatment with decitabine and dasatinib after allogenic hematopoietic stem cell transplantation for myeloid sarcoma.Methods A 29-year-old male patient was diagnosed with abdominal myeloid sarcoma and acute myeloid leukemia with c-kit mutation and t(8;21).Allogeneic hematopoietic stem cell transplantation was performed after inducted remission.The conditioning regimen was decitabine + FLAG + modified Bu/Cy.Prophylaxis of GVHD was performed with cyclosporine mycophenolate mofetil and short-term methotrexate.The patient received 11.73 × 108 mononucleated cells/kg and 17.59 × 106CD34+ cells/kg from donor.At Day 13 post-transplantation,neutrophils reached 0.5 × 109/L and platelet count was 20 × 109/L.Decitabine was prescribed since Day 50 post-transplantation monthly for 5 courses.And dasatinib was offered orally since Day 100 for 4 months.Results It was followed up to 16 months post-transplantation.There were no obvious abnormalities of bone marrow cytology,AML/ETO fusion gene quantification,cerebrospinal fluid or abdominal enhanced computed tomography (CT).Conclusions Hematopoietic stem cell transplantation is an effective treatment for myeloid sarcoma.Decitabine has some efficacy for myeloid sarcoma and it may be used for maintenance treatment after transplantation.Tyrosine kinase inhibitors reduce recurrence in myeloid sarcoma with c-kit mutation.The treatment of decitabine and dasatinib after allogeneic hematopoietic stem cell transplantation yield excellent outcomes.This is the first report in domestic and foreign literatures.

OBJECTIVETo analyze the clinical features and genetic cause for a family affected with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

METHODSClinical manifestations, neuroimaging, and genetic analysis were performed.

RESULTSThe main clinical features have included stroke, emotional disturbance and history of migraine without progressive memory impairment. A positive family history was confirmed. Cranial MRI has revealed multi-infarct lesions and white matter hyperintensity involving bilateral basal ganglia, subcortex and brain stem. All such features were in keeping with the diagnosis of CADASIL. A rare 2182C>T mutation in exon 14 of the NOTCH3 gene was identified in all available cases.

CONCLUSIONBoth clinical and molecular features suggested that the family has been affected with CADASIL.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Migraine Disorders ; genetics ; Receptor, Notch3 ; Receptors, Notch ; genetics

Objective To analysis the MRI features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), to improve the understanding of MRI manifestations of this disease. Meth?ods The clinical manifestations, neuroimaging analysis and genetic analysis were performed in the CADASIL pedigree proband and his families. Results Five of six cases were confirmed with C2182T mutation on exon 14 of the NOTCH3, of which three cases were diagnosed by MRI. Brain MRI findings included bilateral symmetric distributed confluent lesions in the subcortical and periventricular white matter in the frontal lobe, hypointensity on T1WI and hyperintensity on both T2WI and T2 FLAIR imaging in four cases. The external capsule was involved in three cases, with hyperintensity on T2WI. Subcortical lacunar lesions (SLLs) were shown in three cases. Lacunar infarction in the basal ganglia and thalamus were presented in four cases. T2WI hyperintensity at the brain stem was found in two cases. Cerebral microbleeds were re?vealed in three cases. There was no O’Sullivan sign in all the six cases. Conclusions There is characteristic change of MRI in CADASIL patients, which may play a very important role in screening these cases.

Objective To investigate the associations of peripheral CD4+ CD25 + CD127low/-regulatory T cells (Treg) with HBV viral load and liver pathology in hepatitis B virus (HBV) carriers.Methods Forty six chronic HBV carriers admitted in the first hospital of Jiaxing during October 2012 and February 2014,and 23 healthy subjects (controls) were enrolled in the study.CD4+ CD25 + CD127low/-Treg in peripheral blood of the two groups were detected by flow cytometry.Ultrasound-guided liver biopsies were performed in chronic HBV carriers and HBV DNA load was determined by real-time PCR method.Independent samples t test was used for the comparison between groups,and Spearman rank correlation or Pearson linear correlation analyses were performed.Results The frequency of the peripheral CD4+ CD25+CD127low/-Treg in 46 HBV carriers was (5.11 ±1.47)％,which was significantly higher than that in healthy controls [(3.46 ± 1.23) ％,t =4.629,P ＜ 0.01].The HBV DNA load in HBV carriers was (6.21 ±1.98)lg copies/mL,which was positively correlated with the CD4+ CD25+ CD127low/-Treg level (r =0.405,P ＜ 0.01).Among 46 HBV carriers,21 (45.65％) were of inflammation grade 2 or above,and 16 (34.78％) were of fibrosis stage 2 or above.Peripheral CD4+ CD25+ CD127low/-Treg level was negatively correlated with inflammation and fibrosis in HBV carriers (r =-0.343 and-0.452,P ＜ 0.05).Conclusion CD4 + CD25 + CD127low/-Treg may be associated with the chronicity of HBV infection and the degree of liver damage.

Objective To investigate the effect of progesterone pretreatment of focal cerebral ischemic and reperfusion injury (fCIRI) and underlying molecular mechanisms.Methods A single intraperitoneal injection of progesterone (8 mg/kg) given 1 h,48 h and 96 h before fCIRI was established in male Sprague-Dawley rats.The number of survival of neurons in hippocampal CA1 region of the ischemiaside,as well as spatial memory function,was detected on days 3-8 after fCIRI.Extracellular-signalregulated kinase 1/2 phosphorylation (p-ERK1/2) and nuclear translocation of p-ERK1/2 in hippocampal CA1 region were examined using western blot.Results The number of survival of neuronal cells was significantly increased in ischemic groups treated with progesterone at 1 h and 48 h pre-fCIRI (164.3 ± 11.0,218.5 ± 9.1 and 142.7 ± 12.1,F =29.4,P ＜ 0.01) compared with fCIRI group treated with vehicle.Likewise,the escape-latency to reach the hidden-platform recorded in day 5 of Morris water maze test was reduced markedly in fCIRI-treatment groups compared with the vehicle group(10.3 ± 11.1,19.2 ±9.6 and 32.4 ± 14.3 ;F =35.8,P ＜0.01).The level of p-ERK1/2 was elevated notably during 24 h to 48 h postprogesterone by western blot,while restored to the baseline at 96 h post-progesterone.Improved nuclear translocation of p-ERK1/2 was observed from 2 h to 48 h post-progesterone.The progesterone receptor antagonist RU486 blocked the exaltation of either intracellular level or nuclear translocation of p-ERK1/2,which was induced by progesterone.Conclusions The pretreatment with progesterone exerts a neuroprotective effect against the ischemia-induced neuronal death and ameliorates the deficits in spatial memory through enhancing the activation of ERK1/2.The neuroprotection derived from pretreatment with progesterone achieves a time window of not less than 48 h,which is progesterone receptor-mediated ERK1/2 signaling pathway-dependent.

Objective To determine the frequency of depression in patients with Parkinson' s disease(PD) and healthy controls over 50 years of age and to analyze the characteristics and influencing factors of PD with depression(PDD) in Nanjing.Methods One hundred and twenty-six PD patients were diagnosed and assessed using Self-rating Depression Scale (SDS) and Hamilton Depression Scale (HAMD).The frequency,characteristics and influencing factors of depression were statistically analyzed,and the factor analysis of HAMD was carried out.Also,one hundred and twenty-four healthy subjects over the age of 50 were selected as the control group.Ressults The incidence of depression in PD group was 48.4％ ( 61/126):15.1％ (19/126) for mild depression,27.8％ (35/126) for moderate depression,5.6％ (7/126) for severe depression.The incidence of depression in the control group was 9.7％ (12/124):5.7％ (7/124) for mild depression,2.4％ (3/124) for moderate depression,1.6％ (2/124) for severe depression.There was a significant difference between these two groups( x2 =45.36,P ＜ 0.01 ).Univariate and Logistic regression analysis revealed that a high frequency of depression occurred in patients with long PD duration,high H-Y stage and UPDRS Ⅲ.According to each factor analysis of HAMD,the scores of cognitive impairment,tardiness,anxiety and sleep disturbances of the PD patients with depressive syndromes were higher than that of the control group.Conclusion Depression is a relatively common complication of PD in Nanjing which is associated with long PD duration,severity of motor disturbances and increasing H-Y stage.

Objective To investigate the mechanism of protective effects of 17-β estradiol on the experimental model of spinal cord injury (SCI) rats.Methods First,the primary astrocytes were cultured and identified.When the third generation astrocytes were cultured,they were induced by H202 whose concentrations were established by the method of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).The cells were randomly divided into five groups:control group; the group of treatment with 400 μmol/L H2O2 for 24 hours; the group of treatment with 20 nmol/L estrogen for 2 hours prior to exposure to 400 μmol/L H2O2 for 24 hours; the group of treatment with 20 nmol/L estrogen for 26 hours and the group of treatment with dimethyl sulfoxide for 26 hours.The proteins which were extracted from these cells after treatments with H2O2 for 24 hours were detected by Western blotting.Results The absorbances of the astrocytes of treatments with H2O2 were reduced( q' =-11.45,P =0.001 ).But exposure to estrogen prior to exposure to H2O2 provided partial restoration of the absorbances (q' =7.025,P =0.0025 ).The absorbances of the astrocytes among different groups showed significant differences( F =69.69,P =0.0025 ).The results suggested that estrogen might increase the cell viability in astrocytes.Compared with the group of treatment cells with H2O2,treatment cells with 17-β estradiol prior to H2O2 exposure down-regulated the expressions of both phosphatase and tensin homologue deleted on chromosome 10 ( PTEN ) ( F =290.003,P =0.001 ) and caspase-3 ( F =46.158,P =0.023 ).And,17-β estradiol treatment of cells increased the levels of p-Akt ( F =49.173,P =0.033 ) and Bcl-2 ( F =115.916,P =0.001 ) when compared with the group of treatment astrocytes with H2O2.Conclusion These findings suggest that the attenuation of PTEN expression mediated by estrogen is associated with an increase in phosphorylation/activation of the Akt and the Bel-2 expressions.These results suggest that the protective effects of 17-β estradiol on the experimental model of SCI rats may depend on the estrogen protection to the astrocytes which may be mediated by decreasing the PTEN expression.

Objective To investigate the distribution and severity of cerebral artery stenosis and the prognosis in elderly patients with acute cerebral infarction using digital subtraction angiography (DSA). Methods The 432 elderly patients with acute cerebral ischemia infarction underwent DSA,and they were divided into two groups: elderly group (n= 320) and non-elderly group (n= 112). The characteristics of distribution and severity of cerebral artery stenosis, the relationship between artery stenosis and relative risk factors, and the prognosis of acute cerebral infarction were analyzed.Results In elderly group, 270 cases (84.3%) had intra- and extra- cranial artery stenosis, of which 98 patients (30.6%) with pure extracranial arterial stenosis, 132 patients (41.3%) with combined extra- and intra-cranial artery stenosis. They were both significantly higher than the corresponding data in non-elderly group [23 cases (20.5%) and 28 cases (25%), P＜0.05 and 0.01]. The prevalences of moderate and severe cerebral artery stenosises were higher in elderly group than in nonelderly group [224 locations (52.1%) vs. 51 locations (40.8%), P＜0. 05]. The number of patients with previous history of cerebrovascular disease was much more and the prognosis was much worse in elderly group than in non-elderly group (both P＜0.05), Conclusions The elderly patients with cerebral infarction have severer cerebral artery stenosis, increased proportion of multivessel disease and poor prognosis. So it is very important to take aggressive treatment as soon as possible, and to make secondary prevention and effective rehabilitation so as to improve their prognosis.