Epilepsies are a group of chronic neurological disorders characterized by spontaneous recurrent seizures caused by abnormal synchronous firing of neurons and transient brain dysfunction. The underlying mechanisms are complex and not yet fully understood. Endoplasmic reticulum (ER) stress, as a condition of excessive accumulation of unfolded and/or misfolded proteins in the ER lumen, has been considered as a pathophysiological mechanism of epilepsy in recent years. ER stress can enhance the protein processing capacity of the ER to restore protein homeostasis through unfolded protein response, which may inhibit protein translation and promote misfolded protein degradation through the ubiquitin-proteasome system. However, persistent ER stress can also cause neuronal apoptosis and loss, which may aggravate the brain damage and epilepsy. This review has summarized the role of ER stress in the pathogenesis of genetic epilepsy.
Humans ; Endoplasmic Reticulum Stress/genetics* ; Unfolded Protein Response ; Endoplasmic Reticulum/pathology* ; Apoptosis ; Epilepsy/genetics*

Objective To investigate the mechanism of white matter damage (WMD) and the neuroprotective effect of Xenon on neonates with WMD.Methods Three-day-old SD rat pups (n =96) were randomly divided into the blank control group (n =24),the WMD control group (n =24),the Xenon intervention group A (n =24) and the Xenon intervention group B (n =24) by random number method according to their birth time.WMD rat models were successfully established by giving intraperitoneal injection of lipopolysaccharide(LPS) 0.05 mg/kg combined with carotid artery ligation and hypoxia for 1 hour in the WMD control group and the Xenon intervention groups.In the control group,only 9 g/L saline (0.05 mg/kg) was injected intraperitoneally,while carotid artery ligation and hypoxia were not administered.Rats in Xenon intervention group A and group B were given inhalation of 500 mL/L Xenon for 3 hours at 0 and 2 hours respectively after establishment of the models.Six rats in each group were randomly selected and decapitated at 0,24,48 and 72 hours after the intervention.The brain white matter on the right was analyzed by using HE staining and myelin basic protein(MBP) immunofluorescence staining,and real-time quantitative polymerase chain reaction was used to detect the expressions level of CLIC4 mRNA.Results (1) Brain tissue pathology:compared with the blank control group,the brain white matter on the right of the WMD control group and the Xenon intervention group A and group B had loose and disordered structure,nuclear pyknosis and cytoplasm loosening.However,the lesions in both Xenon intervention group A and group B were significantly less than those in the WMD control group,and there was no significant difference between the Xenon intervention group A and group B.(2) MBP measurement:the number of MBP-positive cells in the brain white matter on the right of WMD control group was significantly lower than that in the blank control group,while compared with WMD control group,they were significantly higher in Xenon intervention group A and group B.(3) CLIC4 mRNA expression level:compared with blank control group,the expressions levels of CLIC4 mRNA at most time point were higher both in the WMD control group and the Xenon intervention group A and group B (all P ＜ 0.05),except the time point 24 h in the Xenon intervention group A.The expressions of CLIC4 mRNA in group A and group B were significantly decreased compared with those in the WMD control group (all P ＜ 0.05).However,there were no significant differences between Xenon intervention group A and group B (P ＞ 0.05).Conclusions The expressions of CLIC4 mRNA in brain tissues on neonatal rats with WMD significantly increased,indicating that the mitochondrial pathway could be one of the pathological processes of WMD.Early Xenon intervention may reduce neonatal WMD by reducing the expression of CLIC4 mRNA,which plays a neuroprotective role.

Objective To investigate the effect of fetoscopic photocoagulation of communicating placental vessels in twin-twin transfusion syndrome(TTTS)(selective or non-selective) on the perinatal outcomes.Methods Six cases of TTTS admitted in our department from Dec.2006 to Jun.2008 underwent fetoscopic photocoagulation of communicating vessels.Under direct real-time sonographic guidance,a 3-mm-diameter fetoscope was percutaneously inserted through the maternal abdominal wall into the amniotic cavity of the recipient twin.A combination of ultrasonographic and fetoscopic vision was used to identify the crossing vessels which were systematically coagulated using Nd:YAG laser fiber or bipolar electrocoagulation.Results All the 6 mothers tolerated the procedure without major complications.Two fetal survival rate was 33.33%.Conclusion Fetoscopic photocoagulation of communicating placental vessels in TTTS can effectively improve perinatal outcomes.

Objective:To evaluate the value of mammography and MRI combined with clinical features in predicting upgrade to malignancy in high-risk breast lesions.Methods:Data from 230 patients who were diagnosed with high-risk breast lesions and underwent both mammography and MRI examinations before biopsy were analyzed retrospectively from Jan 2017 to Mar 2018 in Fudan University Shanghai Cancer Hospital. The imaging features of both mammography and MRI were analyzed, and the association between mammography, MRI and clinical features were evaluated using pathology as the gold standard. Independent t test and χ 2 test were used to compare the difference of clinical and imaging features between upgrade and non-upgrade groups, using receiver operating characteristic (ROC) curve to test the diagnostic value between mammography and MRI. Binary logistic regression was used to evaluate the correlation between upgrade and clinical, imaging findings. Results:Two hundred and thirty patients had 230 lesions, and 47 cases had atypia upgrade to malignancy during second surgery (upgrade rate was 20.4%). There were statistically significant differences in age, maximum diameter of lesion, and menopausal status between the upgraded and non-upgraded groups ( P<0.05). There was no statistically significant difference in mammographic features between two groups ( P>0.05), while there was statistically significant difference in breast MRI features and background parenchymal enhancement ( P<0.05). For the diagnostic value in predicting upgrade of high-risk lesions, MRI was better than mammography (the areas under ROC curve were 0.913 and 0.606, Z=6.919, P<0.01). Single factor analysis showed that age, lesion size, menopausal status, MRI negative and background parenchymal enhancement on MRI were significantly different for upgrade to malignancy ( P<0.05). Multiple factors analysis showed age and background parenchymal enhancement on MRI were independent factors for predicting upgrade ( P<0.01). Conclusion:For the upgrade to malignancy in high-risk lesions, the diagnostic value of MRI is better than mammography. The elder age and moderate or marked background parenchymal enhancement on MRI may serve as useful predictors of upgrade.

Objective To investigate high risk human papillomavirus(HR-HPV)prevalence among married women in Beijing and to study the high risk flactors.nethods During March 2007 to September 2008.a total of 6185 married women sampled from 137 communities in 12 districts were screened bv HR-HPV DNA test and cytogical test.The interview was carried out with unified questionnaires.The databage was set up and twice entered in EpiDam 3.0.After checked up,the data were analyzed in SPSS 15.0.Results (1) The HR-HPV infection rate was 9.89%.The HR-HPV infection rate of the city zone,the suburb and the exurb were 9.34%,10.51% and 9.51% (P>0.05).The HR-HPV infection rate of the native and the oudander were 9.53%,11.30% (P<0.05).(2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups,which was the highest(11.21%) in 30 to 34 age group;then the rate was descended as the age raising,the rate of 50 to 54 age group was the lowest(7.78%).(3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month.possessing more than 1 sexual partner of her husband,outlander and hish levels of education.(4) The prevalence of cervical intraepithelial neoplasia(CIN)in HR-HPV positive group wag significantly higher than that in HR-HPV negative group(29.76% vs 3.32%,P<0.01).Conclusions(1)The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution.(2)The hish risk population which should strengthen screening was the married bearing-age women with high level of family income,outlander,high levels of education and her husband possessing more than 1 sexual partner.(3)HR-HPV infection is the main risk factor for CIN and cervical cancer.while does not provide a causal relationship with them.The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.