Effect of overexpression of superoxide dismutase 1 mutant genes G41S and G41D on cognitive behavior in medial prefrontal cortex of mice / 中华行为医学与脑科学杂志

Objective:To investigate the effects of superoxide dismutase 1 (SOD1) mutations G41D and G41S on the cognitive behavior of mice.Methods:The recombinant adeno-associated virus (rAAV) which overexpressed human SOD1WT, SOD1G41S, SOD1G41D and the blank virus without the target gene were constructed, then they were stereotaxic injected into mice bilateral medial prefrontal cortex (mPFC) area respectively.According to the difference of injected virus, they were divided into CONTROL group, SOD1WT group, SOD1G41S group and SOD1G41D group ( n=16 in each group). One month later, open field test, Y-maze spontaneous alternation experiment, three box social interaction experiment and trace fear conditioning test were conducted to observe the effect of mutant gene on cognitive behavior of mice. Results:In the open field test, the movement distance of SOD1WT group((39.67±6.04)m)was significantly higher than that of SOD1G41D group((28.47±6.92)m, P=0.034). In the Y-maze spontaneous alternations experiment, the number of arm entries and actual alternations of arm entries of SOD1WT group((40.56±10.12)times, (32.63±8.19)times)and SOD1G41S group((36.75±9.43)times, (29.06±8.32)times)were significantly higher than those of SOD1G41D group((24.50±11.30)times, (18.38±9.09)times, P<0.05). In the three-compartment social experiment, there was no statistical difference between the residence time of SOD1G41D group in the area containing mouse ((279.08±134.94) s) and the empty metal cage area ((218.54±125.63) s) ( t=1.313, P=0.199). SOD1WT group and SOD1G41S group showed no statistical difference in the residence time in the regions of the unfamiliar mouse 1((253.07±55.60)s, (253.20±57.61)s) and the unfamiliar mouse 2 ((243.44±55.33) s, (239.76±67.49) s) ( P>0.05), and SOD1WT group and SOD1G41S group presented new social barrier.In the test stage of trace fear condition task, the percentage of freezing time of SOD1G41S group was significantly higher than that of other experimental groups and CONTROL group ( P<0.05). Conclusion:SOD1G41S and SOD1G41D have significantly changed the cognitive behavior of mice, and the two types of mutations at the same site have significant differences in the cognitive behavior changes.

Summary of the Twenty-eighth International Conference on Amyotrophic Lateral Sclerosis-Motor Neuron Disease / 中华神经科杂志

The 28th International Conference on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Boston from December 8 to 10, 2017. The conference covered 23 topics, 102 special topics and 446 papers. This article briefly introduces some topics of the conference, involving basic research, clinical research and clinical trials. Among these, basic studies include genetics, cell biology and pathology, and superoxide dismutase1 gene ALS related pathology; clinical studies include the progression of ALS disease, cognitive behavioral disorders, and biological markers.

Study of a CADASIL family with migraine as the presenting symptom / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and genetic cause for a family affected with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).</p><p><b>METHODS</b>Clinical manifestations, neuroimaging, and genetic analysis were performed.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>Both clinical and molecular features suggested that the family has been affected with CADASIL.</p>

Neuroimaging study of CADASIL pedigree with performance of familial migraine / 中国神经精神疾病杂志

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.

Clinical features and risk factors of anastomotic leakage after radical esophagectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and risk factors of anastomotic leakage after radical esophagectomy of esophageal carcinoma.</p><p><b>METHODS</b>The clinical data of 547 esophageal cancer patients underwent radical esophagectomy in Tianjin Medical University Cancer Hospital from January 2012 to December 2013 was analyzed retrospectively. There were 421 male and 126 female patients, with a median age of 65 years (ranging from 29 to 82 years). There were 155 cases of upper esophageal carcinoma, 340 cases of middle esophageal carcinoma and 52 cases of lower esophageal carcinoma. The surgical procedures included 41 cases completed through Sweet, 145 cases completed through McKeown, 279 cases completed through Ivor Lewis, 82 cases completed through minimally invasive esophagectomy. Moreover, 24 of 547 cases underwent preoperative neoadjuvant radiochemotherapy. χ² test and Cox's proportional hazards regression model were used for univariate analysis and multivariate analysis of the risk factors of postoperative anastomotic leakage.</p><p><b>RESULTS</b>Twenty-seven of 547 cases with esophagectomy occurred anastomotic leakage and the incidence rate was 4.94% (27/547). One of 27 cases died and the mortality rate was 3.70% (1/27). The time of anastomotic leakage found was 4 to 45 days, with a median time of 10 days. There were 0 case of early leakage, 20 cases of mid-term leakage, 7 cases of late leakage. Three of 27 cases with anastomotic leakage had tracheoesophageal fistula, while 3 cases had contralateral pleural fistula. As to the incidence rate of anastomotic leakage, there was statistically significant difference between cervical anastomotic leakage (8.14%, 18/221) and intrathoracic anastomotic leakage (2.76%, 9/326) (χ² =7.41, P=0.000), among Sweet (4.88%, 2/41), McKeown (9.66%, 14/145), Ivor Lewis (2.51%, 7/279) and MIE (4.88%, 4/82) (χ² =21.48, P=0.000), and between with (16.67%, 4/24) and without (4.40%, 23/523) neoadjuvant radiochemotherapy (χ² =9.20, P=0.000). The multivariate analysis showed that anastomotic site (HR=2.594, P=0.048), surgical approach (HR=5.689, P=0.003) and preoperative neoadjuvant radiochemotherapy (HR=3.604, P=0.027) are independent risk factors for anastomotic leakage after esophagectomy.</p><p><b>CONCLUSIONS</b>The mid-term anastomotic leakage after esophagectomy occurs higher. McKeown is a main surgical procedure and neoadjuvant radiochemotherapy is an important factor for the anastomotic leakage.</p>