Objective:To explore the seizure-onset intracranial electroencephalogram patterns in mesial temporal lobe epilepsy (MTLE) by stereo-electroencephalography (SEEG).Methods:The clinical data of 16 patients with focal epilepsy admitted to Epilepsy Center, Shanghai Deji Hospital from March 2017 to December 2019 were retrospectively analyzed. Tonic discharge was taken as sign of the initial period; transition period from the interictal period to the initial period was named as the preictal period, characterized by clonic discharge that was different from the interictal period. The initial and preictal discharge patterns were described, and their corresponding relationship were studied; at the same time, the spatial distribution and synchrony of the discharges at initial and preictal periods were observed.Results:One hundred and thirty-two seizures were recorded in these 16 patients. Two patterns at initial period were noted: low-voltage fast activity (LVFA)+slow depolarizing shifts (SPSs, n=29, 22%), and rhythmic activity (RA) of low-medium amplitude without SPSs ( n=103, 78%); spatial spread of LVFA+SPSs was much wilder than that of RA. In addition, 3 patterns at preictal period were summarized: hypersynchronous (HYP, n=93, 70.5%, most commonly found in the anterior hippocampus [87/219]), sentinel spike ( n=22, 16.7%), and pattern of smooth transition from the interictal period to the initial period ( n=17, 12.9%). No special correspondence in discharge patterns was noted between the initial period and preictal period. Conclusion:Seizure is a process of gradual evolution from interictal period, preictal period to initial period. HYP potential is the most common pattern of seizure in MTLE at preictal stage, mainly appeared in the anterior hippocampus; RA potential is the most common pattern of seizure in MTLE at initial stage, with lower frequency and more limited spatial spread.

Objective:To explore the seizure-onset intracranial electroencephalogram patterns in mesial temporal lobe epilepsy (MTLE) by stereo-electroencephalography (SEEG).Methods:The clinical data of 16 patients with focal epilepsy admitted to Epilepsy Center, Shanghai Deji Hospital from March 2017 to December 2019 were retrospectively analyzed. Tonic discharge was taken as sign of the initial period; transition period from the interictal period to the initial period was named as the preictal period, characterized by clonic discharge that was different from the interictal period. The initial and preictal discharge patterns were described, and their corresponding relationship were studied; at the same time, the spatial distribution and synchrony of the discharges at initial and preictal periods were observed.Results:One hundred and thirty-two seizures were recorded in these 16 patients. Two patterns at initial period were noted: low-voltage fast activity (LVFA)+slow depolarizing shifts (SPSs, n=29, 22%), and rhythmic activity (RA) of low-medium amplitude without SPSs ( n=103, 78%); spatial spread of LVFA+SPSs was much wilder than that of RA. In addition, 3 patterns at preictal period were summarized: hypersynchronous (HYP, n=93, 70.5%, most commonly found in the anterior hippocampus [87/219]), sentinel spike ( n=22, 16.7%), and pattern of smooth transition from the interictal period to the initial period ( n=17, 12.9%). No special correspondence in discharge patterns was noted between the initial period and preictal period. Conclusion:Seizure is a process of gradual evolution from interictal period, preictal period to initial period. HYP potential is the most common pattern of seizure in MTLE at preictal stage, mainly appeared in the anterior hippocampus; RA potential is the most common pattern of seizure in MTLE at initial stage, with lower frequency and more limited spatial spread.

Objective:To analyze the clinical manifestations, gene mutation characteristics and treatment effects of patients with GATOR1 complex-related epilepsy, and to explore the diagnosis and treatment of this disease.Methods:The medical history, electroencephalogram, brain imaging, genetic test results, treatment and follow-up data of patients with GATOR1 complex-related epilepsy who attended the Children′s Hospital Affiliated to Capital Institute of Pediatrics, Beijing Tsinghua Changgung Hospital, and Shanghai Deji Hospital from May 2017 to July 2022 were retrospectively analyzed.Results:A total of 16 patients with GATOR1 complex-related epilepsy were collected, including 7 males and 9 females. The age of onset of epilepsy was from 2 months to 14 years. Ten cases had focal seizures only, 2 cases had generalized seizures only, and 4 cases had coexistence of focal seizures and generalized seizures, of which generalized seizures included generalized tonic-clonic seizure, spastic seizure, and myoclonic seizure. Among the 16 patients, 2 had infantile spasms, 3 had familial focal epilepsy with variable focus, and 1 had sleep related hyperkinetic epilepsy. Electroencephalogram intervals suggested multiple brain areas discharge or diffuse discharge. A total of 13 DEPDC5 gene mutation sites, 1 NPRL2 gene mutation site, and 2 NPRL3 gene mutation sites were found; 4 sites of DEPDC5 gene were reported sites, the rest were unreported; all mutations had pathogenic significance; 8 cases had nonsense mutation, 1 case had large fragment deletion, 4 cases had frameshift mutation, 1 case had integer mutation, 2 cases had splicing mutation; 13 cases′ mutation was inherited from parents, 2 cases had new mutation, and 1 case had unverified mutation. Magnetic resonance imaging (MRI) showed 5 of the 16 patients were normal, and 11 had abnormal cerebral cortex structure, manifested as bottom-of-sulcus focal cortical dysplasia (FCD), abnormal formation of sulci and (or) gyri with or without ill-defined gray-white matter and malformation of cortical dysplasia of the bilateral brain. Seven patients underwent stereotactic electroencephalogram (SEEG) monitoring, and the SEEG showed low-amplitude fast rhythm at the beginning in 6 patients, of whom 5 cases started from the frontal lobe, and 1 case started from the parietal lobe. Eight patients were only treated with drugs, 1 with single-drug therapy and the rest with multi-drug combination therapy. Eight patients underwent surgery. Among them, 5 patients with DEPDC5 gene mutation underwent epileptogenic cortex excising after SEEG monitoring, and postoperative pathological examinations showed FCDⅡ, FCDⅢ or non-specific changes; 1 patient was waiting for surgery. One patient with NPRL3 gene mutation underwent epileptogenic foci resection and postoperative pathological examinations showed FCDⅡa; the other patient with NPRL3 gene mutation underwent radiofrequency thermocoagulation after SEEG monitoring. Follow-up showed that 3 patients were seizure-free with drug treatment, and 4 patients had fewer seizures after drug treatment. Six cases underwent epileptic foci resection. Five of them were assisted by SEEG to locate the epileptic foci before surgery and were seizure-free after the operation, but the range of surgical resection was wider than the abnormal range shown by MRI; whereas 1 case who was not assisted by SEEG showed no improvement. There was still 1 case who underwent SEEG-guided radiofrequency thermocoagulation and had no improvement after operation. Conclusions:GATOR1 complex-related epilepsy mostly manifests as focal seizures. SEEG shows that seizures originate from the frontal lobe more often, and cortical developmental abnormalities are often found. DEPDC5 gene mutations are the most common ones, mostly inherited from parents, with high incomplete penetrance rate. Therefore, genetic testing is recommended for non-acquired brain structural abnormalities. For those who are refractory to drugs, a radical cure can be obtained by resection of the epileptogenic foci after preoperative evaluation.

OBJECTIVE: To analyze the clinical characteristics of patients with emergency in-hospital cardiac arrest (IHCA) in Kashgar, Xinjiang Uygur Autonomous Region and the factors affecting the success rate of cardiopulmonary resuscitation. METHODS: Retrospectively selected patients who had cardiac arrest and cardiopulmonary resuscitation in the emergency department of the People's Hospital of 6 counties and cities in Kashgar area from January 2019 to January 2022. The clinical data of all patients were collected, including gender, age, major underlying diseases, the beginning and duration of resuscitation, the number of electric defibrillation acute physiology and chronic health evaluation II (APACHE II). According to whether the resuscitation was successful, all patients were divided into successful resuscitation group and failed resuscitation group. The clinical characteristics of the two groups were compared. Then, the influencing factors of the success rate of cardiopulmonary resuscitation in IHCA patients were analyzed by binary Logistic regression. RESULTS: A total of 1 376 patients were enrolled, including 1 117 cases of failed resuscitation and 259 cases of successful resuscitation. The success rate of resuscitation was 18.82%. Compared with the resuscitation failure group, the patients in the successful resuscitation group were younger (age: 49.10±20.99 vs. 58.44±18.32), the resuscitation start time was earlier [resuscitation start time ≤ 5 minutes: 76.45% (198/259) vs. 66.61% (744/1 117)], the proportion of cardiovascular and cerebrovascular diseases was lower [cardiovascular disease: 49.42% (128/259) vs. 58.19% (650/1 117), cerebrovascular disease: 17.37% (45/259) vs. 21.58% (241/1 117)], the number of electric defibrillation was lower [times: 0 (0, 2) vs. 1 (0, 1)], the proportion of endotracheal intubation was more [80.31% (208/259) vs. 55.60% (621/1 117)], APACHE II score was lower (13.75±8.03 vs. 17.90±4.63), and the difference was statistically significant (all P < 0.01). Binary Logistic regression analysis showed that age, start time of resuscitation, ventilation mode and APACHE II score were protective factors affecting the success rate of cardiopulmonary resuscitation in patients with emergency IHCA [age: odds ratio (OR) = 0.982, 95% confidence interval (95%CI) was 0.973-0.991, P < 0.001; resuscitation start time ≤ 5 minutes: OR = 0.629, 95%CI was 0.409-0.966, P = 0.034; tracheal intubation assisted ventilation: OR = 0.243, 95%CI was 0.149-0.397, P < 0.001; low APACHE II score: OR = 0.871, 95%CI was 0.836-0.907, P < 0.001], while underlying diseases (cardiovascular diseases) are a risk factor affecting the success rate of cardiopulmonary resuscitation (OR = 1.190, 95%CI was 1.015-1.395, P = 0.036). CONCLUSIONS Age, resuscitation start time, ventilation mode, APACHE II score and major underlying diseases (cardiovascular diseases) have a greater impact on the success rate of resuscitation in IHCA patients. The above factors are conducive to improving or formulating more effective rescue strategies for IHCA patients, so as to achieve the purpose of improving the success rate of clinical treatment.
Humans ; Adult ; Middle Aged ; Aged ; Retrospective Studies ; Cardiopulmonary Resuscitation ; Heart Arrest/therapy* ; Electric Countershock ; Hospitals

Objective:To explore the relationship between body mass index (BMI) and clinicopathological features and prognosis of gallbladder cancer.Methods:The clinical and follow-up data of three hundred and eighty-six patients of gallbladder carcinoma were retrospectively, who were treated from January 2008 to December 2013 in the Department of Hepatobiliary Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University. According to the guidelines for prevention and control of overweight and obesity in Chinese adults, the patients were divided into three groups: normal weight group(BMI<23.5 kg/m 2, 239 cases, accounting for 61.9%), overweight group (23.5 kg/m 2≤BMI<27.5 kg/m 2, 127 cases, accounting for 32.9%) and obesity group(BMI≥27.5 kg/m 2, 20 cases, accounting for 5.18%). The clinicopathological factors(gender, age, diabetes mellitus, hypertension, gallbladder related diseases, jaundice, tumor location, TMN, postoperative days, tissue differentiation, liver invasion, intraoperative blood transfusion, complications) of the three groups were compared, and the relationship between BMI and 5-year survival rate was analyzed. Measurement data with normal distribution were indicated as mean±standard deviation( Mean± SD), measurement data with skewed distribution were represented as M( P25, P75). Nonparametric rank sum test was used for measurement data. Categorical variables were compared by the chi-square test or Fisher probability method. The survival curve was drawn by the Kaplan-Meier method. The univariate analysis and multivariate analysis of prognosis were respectively done using the Log-rank test and COX regression model. Results:The median survival time of 386 patients with gallbladder cancer was 12.1 months. The overall survival rates of 1, 3 and 5 years were 51.8%, 25.2% and 16.8%, respectively. Univariate survival analysis showed that age, jaundice, accidental gallbladder cancer, tumor location, TMN, surgical method, tissue differentiation, liver invasion, intraoperative blood transfusion, and complications affected the 5-year survival rate ( χ2=12.24, 30.87, 37.01, 7.92, 104.23, 118.76, 12.05, 49.12, 6.85, 12.24, P<0.05). BMI was related to hypertension, but it had no significant effect on the 5-year survival rate. However, with the increase of BMI, the 5-year survival rate increased (16.3% vs 16.7% vs 23.3%, P=0.774). Multivariate survival analysis showed that surgical method( OR=1.441, 95% CI: 1.219-1.705), liver invasion( OR=1.625, 95% CI: 1.264-2.091), M stage( OR=1.664, 95% CI: 1.070-2.587), and N stage( OR=1.511, 95% CI: 1.218-1.875) were independent risk factors for prognosis in this group of patients ( P<0.05), and BMI was not an independent risk factor ( P=0.901). Conclusions:BMI has no significant effect on the prognosis of patients with gallbladder cancer. Obese patients with gallbladder cancer do not need to wait for weight loss before surgery.

Ricin is a highly toxic type 2 ribosome-inactivating protein (RIP) which is extracted from the seeds of castor beans. Ricin is considered a potential bioterror agent and no effective antidote for ricin exists so far. In this study, by structural modification of a retrograde transport blocker Retro-2, a series of novel compounds were obtained. The primary screen revealed that compound has an improved anti-ricin activity compare to positive control. pre-exposure evaluation in Madin-Darby Canine Kidney (MDCK) cells demonstrated that is a powerful anti-ricin compound with an EC of 41.05 nmol/L against one LC (lethal concentration, 5.56 ng/mL) of ricin. Further studies surprisingly indicated that confers post-exposure activity against ricin intoxication. An study showed that 1 h post-exposure administration of can improve the survival rate as well as delay the death of ricin-intoxicated mice. A drug combination of with monoclonal antibody mAb4C13 rescued mice from one LD (lethal dose) ricin challenge and the survival rate of tested animals is 100%. These results represent, for the first time, indication that small molecule retrograde transport blocker confers both and post-exposure protection against ricin and therefore provides a promising candidate for the development of anti-ricin medicines.

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further and studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

BACKGROUND: Lung cancer rates among women in rural Xuanwei and Fuyuan counties in eastern Yunnan province, China, are among the highest in the world, even though almost all women are non-smokers, and they tend to develop lung cancer at a younger age than other locations by roughly 5 yr-10 yr. This study investigated the survival of lung cancer patients among female never-smokers. METHODS: The female never-smokers, who had lived for many years in Xuanwei and Fuyuan counties, with lung cancer newly-diagnosed between July 2006 to March 2010, were followed up through the end of 2016. Age-standardized relative survival for all cases was calculated using local life table. The Kaplan-Meier method and Log-rank test were used to analyze the relationship between the variables and the prognosis in univariate analysis. Cox regression analysis was employed in the multivariate analysis. RESULTS: Among 1,250 total subjects, 1,075 died and the remaining 175 were censored during the follow-up, with a median follow-up period of 69 months (95%CI: 61.9-76.0). Overall, the mean age was (54.8 ±10.9) yr, with variable clinical stages: 3.5% of cases were stage I, 8.7% stage II, 20.7% stage III, 29.7% stage IV, and 37.4% stage unknown. The 645 patients(51.6%) with cyto-histological diagnosis contains 303 with Squamous cell carcinoma, and 231 with adenocarcinoma, 24 with small cell, 43 with other specified type and 39 with unknown histological type. Only 215 (17.2%) patients received surgery, 487 (39.0%) were treated without surgery, and 548 (43.8%) did not receive any specific anticancer therapy. The 5-year observed survival rate and age-standardized relative survival were 8.9% (95%CI: 7.0-10.6), and 10.1% (95%CI: 3.7-20.5) respectively, with a median survival of 13.2 months. The 5-year survival rates were 41.1% for stage I, 22.4% for stage II, 5.3% for stage III, 1.3% for stage IV, 11.2% for missing stage, 17.9% for adenocarcinoma, and 5.6% for squamous cell carcinoma respectively. Surgery significantly improved 5-year survival rate compared with non-surgery (34.8% vs 3.2%, P<0.001). The patients with non-treatment, aged 65 years and older, living in rural areas and farmer with low socioeconomic status had poorer survival, whereas the patients treated in provincial hospitals and chest X-ray screening had better survival. Cox multivariate analysis further showed that stage of tumor-node-metastasis (TNM), treatment status, hospital-level, and X-ray screening were factors correlated with survival. CONCLUSIONS Patients with lung cancer among female never-smokers in Xuanwei and Fuyuan experience poorer survival, because they are less likely to be diagnosed at early stage, as well as less likely to receive surgery and comprehensive treatment. Furthermore low socioeconomic status and poor health security are also responsible for the low survival.

OBJECTIVETo explore the clinical and genetic characteristics of patients with dentatorubro-pallidoluysian atrophy (DRPLA).

METHODSDNA analysis for DRPLA gene was performed in two patients. Clinical features and genetic testing of Chinese DRPLA patients reported in the literature were reviewed in terms of initial symptoms, CAG repeat and age of onset.

RESULTSBoth families were confirmed by genetic analysis. In family 1, the number of CAG repeat in the proband, his brother and his mother was determined respectively as 8/65, 8/53 and 8/18. In family 2, the number of CAG repeat was respectively 13/63, 13/18, 18/52 and 13/13 in the proband, his brother, his father and his mother. The size of the expanded CAG repeats has inversely correlated with the age at onset (P<0.05, r=- 0.555). The age at onset of epilepsy was 10 and that for the onset of ataxia is forty years in initial symptom.

CONCLUSIONThe clinical characteristics of DRPLA include epilepsy, ataxia and cognitive impairment. The initial symptoms are epilepsy in adolescence and ataxia in adults. The size of expanded CAG repeats inversely correlates with the age at onset. The initial symptoms are different with different age of onset. It is difficult to diagnose DRPLA at an early stage.

Adolescent ; Adult ; Aged ; Atrophy ; genetics ; Basal Ganglia Diseases ; diagnosis ; genetics ; DNA Mutational Analysis ; Dentate Gyrus ; pathology ; Family Health ; Female ; Globus Pallidus ; pathology ; Humans ; Male ; Middle Aged ; Nerve Tissue Proteins ; genetics ; Pedigree ; Trinucleotide Repeat Expansion ; genetics ; Young Adult

Objective To investigate the effects of circadian rhythm on interictal epileptiform discharges in patients with localization-related epilepsy.Methods Patients diagnosed with epilepsy in Sanbo Brain Hospital from January 2011 to January 2012 participated in this study.All patients were subjected to comprehensive evaluation,which included prolonged video-electroencephalogram (EEG),magnetic resonance imaging.Intracranial electrodes,PET,SPECT were also adopted if necessary.Circadian rhythm was divided into four stages:REM,NREM Ⅰ-Ⅱ,NREM Ⅲ-Ⅳ,and waking.The amount and distribution of ⅡD were compared by ANOVA.Results Significant differences in the amount and distribution of ⅡD were found among NREM Ⅰ-Ⅱ,NREM Ⅲ-Ⅳ,REM,and waking.However,no differences in the amount and distribution of ⅡD were noted between NREM Ⅰ-Ⅱ and NREM Ⅲ-Ⅳ as well as between REM and waking.Conclusion The amount of ⅡD is higher in NREM than in REM and waking;thus,NREM is more sensitive to diagnose epilepsy.The distribution of ⅡD in REM and waking is more restricted than that in NREM.