Objective To study any protection against hippocampal neuron damage induced by epilepsy (SE) provided by transcutaneous stimulation (TNS) of the trigeminal nerve and to document any effect of such stimulation on the expression of glutamic acid decarboxylase (GAD) 65/67.Methods Pilocarpine injection was used to induce epilepsy in healthy male Sprague-Dawley rats which were then randomly divided into a treatment group and a model group.Rats which had not received the pilocarpine injection served as normal controls.In the treatment group the rats were given electrostimulation for one month after the first spontaneous seizure following the injection of pilocarpine.In the model group they were given sham TNS for one month.After the month of stimula-tion,immunohistochemistry was used to detect the expression of GAD65/67 in the hippocampus.Terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays and Nissl staining were applied to deter-mine apoptosis and neuron loss in the hippocampus.Results Significantly less apoptosis was observed in the treatment group than in model group at 24 h,48 h and 72 h post-injection.Compared to the model group,average GAD65/67 expression had increased significantly in the treatment group at 24 h,72 h,1 week,2 weeks and 4 weeks post-stimulation.GAD65 expression reached its peak from 72 h to 1 week post-stimulation,then decreased to the level of the control group by 4 weeks post-stimulation.The expression of GAD67 remained elevated at all the time points employed.Conclusions TNS can significantly protect hippocampal neurons from damage in epilepsy,at least in rats.The underlying anti-epileptic and neuroprotective mechanisms may involve increased inhibitory transmission induced by the stimulation.

Neonatal necrotizing enterocolitis (NEC) is the most common neonatal gastrointestinal disease and has most lethal effect. In recent years,with the development of the neonatal intensive care unit,the survival rate of premature infants is increased, but the incidence rate of NEC is also increasing. At the present stage,the etiology of NEC is still not completely clear,which greatly limits the prevention and treatment of NEC. Risk factors including premature birth, infection, bacterial colonization, hypoxia ischemia,inflammatory reaction and enteral nutrition are summarized in this paper to provide basis for clinical diagnosis,treatment and prevention of NEC.

Objective:To analyze the clinical and pathological features of asymptomatic primary hyperparathyroidism (PHPT) .Methods:A retrospective analysis was carried out in terms of the clinical characteristics and pathological data in 30 patients with asymptomatic PHPT and 86 patients with typical PHPT hospitalized in the Department of Endocrinology and General Surgery of Beijing Jishuitan Hospital from Jan. 2013 to Dec. 2018. There were 7 males (23.3%) and 23 females (76.7%) , with a male to female ratio of 1:3.3. The average age was 56.9±13.3 years. In typical PHPT group, there were 32 males (37.2%) and 54 females (62.8%) , with the average age of 46.4±17.0 years. Bone metabolism indicators included bone density and bone biochemical markers (parathyroid hormone, 25-hydroxyvitamin D and alkaline phosphatase) . The t test was used to compare normally distributed variables, the Mann-Whitney rank sum test was used to compare skewed distributed variables, and the χ 2 test was used to compare enumeration data. Results:The median serum parathyroid hormone and alkaline phosphatase were 144.2 (108.1, 207.0) pg/ml and 80.0 (53.7, 105.5) IU/L respectively, the average serum concentration of calcium was 2.80±0.20 mmol/L, which were significantly lower than those of the classic group ( P<0.05) . The median serum 25-hydroxyvitamin D was 12.14 (7.87, 14.38) ng/ml, which was higher than that of the classic group ( P<0.001) . Ten patients (33.3%) developed osteoporosis, and the incidence was lower than that of the classic group ( P< 0.001) . The median tumor weight was 0.80 (0.25, 1.98) g, significantly smaller than that in the classical group ( P=0.003) . There were 26 cases (86.7%, including 2 atypical parathyroid adenomas) of parathyroid adenomas and 4 cases (13.3%) of hyperplasia. Conclusions:The asymptomatic PHPT has the same sex ratio as the classic type, mainly female, but the average age is significantly higher than that in the classic type. Although asymptomatic PHPT in this study are all benign lesions, abnormal bone biochemical indicators, especially vitamin D deficiency, are common, which also lead to osteoporosis.

Objection: To analyze the factors affecting the prognosis of patients with gastric neuroendocrine neoplasms (G-NENs) by using the surveillance of National Cancer Institute (NCI) of America, Epidemiology and End Results (SEER) database, and to construct a prognostic Nomogram model for individualized prediction of prognosis in patients with G-NENs. Methods: The clinical data of 2720 G-NENs patients with complete follow-up data from 2010 to 2015 in the SEER database were collected. The prognostic Nomogram model was constructed based on independent risk factors determined by survival analysis. The consistency index (C-index) and calibration curve were used to evaluate its accuracy.Area under the curve (AUC) was used to compare the evaluation value between the Nomogram and the 7th edition of AJCC TNM staging. Results: The 1-, 3-, and 5-year survival rates of 2,720 patients with G-NENs were 88.14%, 79.09%, and 71.86%, respectively. Multivariate COX regression analysis showed that gender, age, marital status, other associated tumors, histological type, tumor grade, T stage, M stage, and surgery were independent risk factors affecting survival time of GNENs patients. The C-index of newly constructed Nomogram prediction model was 0.816, which was significantly higher than 0.702 of the 7thAJCC TNM staging (P<0.001), and the 1-, 3- and 5-year calibration curves showed a good agreement between predicted survival and actual survival. The AUC for 1-, 3- and 5-year survival by Nomogram prognostic model was 0.800, 0.811, and 0.820, which was higher than 0.650, 0.688 and 0.698 of the 7th AJCC TNM staging, and the differences were statistically significant (Z= 6.600, 8.085, 9.632, all P<0.0001). Conclusion: The Nomogram prediction model drawn in this study has a high prognostic value and can individually predict the survival rate of G-NENs patients, which is helpful for clinical treatment decision-making and clinical research options.

Objective: To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors. Methods: Eight-week-old C57BL/6J male mice were fed a high-fat diet for 12 successive weeks to construct the obese model. C57BL/6J male mice were fed a standard chow diet to construct normal control group. After 8 weeks of intervention with ginsenoside rg3, the food intake, body weight, body fat mass, blood sugar, and lipid profiles of the mice in each group were detected. Hematoxylin and eosin (HE) staining was used to observe the histological morphology of the adipose tissues. Real-time poly-merase chain reaction (RT-PCR) and Western blotting (WB) were applied to detect the gene and protein expression levels of peroxisome proliferators-activated receptor gama (PPARγ), Peroxisome proliferator-activated receptor-gamma coactivator -1alpha (PGC-1α), PR domain containing 16 (PRDM16), and uncoupling protein 1 (UCP-1).Results: Compared to normal control group mice, the body weight, food intake, body fat composition, and blood lipid levels of model group mice increased significantly. After 8 weeks of intervention with ginsenoside rg3, body weight, body fat composition, food intake, and blood lipid profiles decreased. HE staining showed that ginsenoside rg3 can improve white adipocyte hypertrophy to a certain extent. RT-PCR and WB demonstrated that ginsenoside rg3 can increase the mRNA and protein expression levels of PPARγ, PGC-1α, PRDM16, and UCP-1 in the adipose tissues of obese mice. Conclusion: The weight reduction effect of ginsenoside rg3 may be related to the promotion of white fat browning.

Objective:To investigate the clinicopathological features, immunophenotype, differential diagnosis, molecular genetic changes and prognosis of salivary gland-type clear cell carcinoma (CCC) of the lung.Methods:Eight cases of salivary gland-type CCC of the lung diagnosed at Fudan University Shanghai Cancer Center and Shanghai Pulmonary Hospital, China from March 2017 to December 2020 were retrieved and analyzed. The pathological sections of these cases were studied using immunohistochemical staining, fluorescence in situ hybridization (FISH), and RNA-seq fusion gene detection based on next generation sequencing technique. The patients were followed up and the relevant literature was reviewed.Results:The 8 patients included 3 males and 5 females, with age ranging from 43 to 64 years (average, 58 years). All patients underwent radical lobectomy and lymph node dissection, while only one had lymph node metastases. The eight patients were followed up for 6 to 45 months, and were all recurrence-free. Histopathologically, the tumor was mainly composed of eosinophilic and clear cells arranged in trabecular, ribbon and nest patterns. Hyalinization was often observed in the stroma around the nest. Immunohistochemical staining showed that 8/8 cases were positive for EMA and CK7; 5/8 cases were positive for p63 and p40; 4/8 cases were positive for SOX10; and the cases were all negative for S-100, SMA and calponin. EWSR1 gene fusion was detected in all cases by FISH. RNA-seq fusion gene was detected in 6 cases based on next generation sequencing. The EWSR1-ATF1 gene fusion was detected in 5 cases, among which one case also had the ATF1-SPTLC2 gene fusion. All 5 cases with EWSR1-ATF1 gene fusion showed that EWSR1 exon 12/13 fused with ATF1 exon 3. And EWSR1-CREM gene fusion was detected in one case.Conclusions:Salivary gland-type CCC of the lung is an extremely rare primary lung tumor arising from the bronchial mucosa. The diagnosis and differential diagnosis of this tumor depend on classic histomorphology, especially the auxiliary detection of EWSR1 fusion gene. The primary treatment choice of this tumor is complete surgical resection. Lymph node metastases may occur, but the overall prognosis is good.

The traditional paradigm of motor-imagery-based brain-computer interface (BCI) is abstract, which cannot effectively guide users to modulate brain activity, thus limiting the activation degree of the sensorimotor cortex. It was found that the motor imagery task of Chinese characters writing was better accepted by users and helped guide them to modulate their sensorimotor rhythms. However, different Chinese characters have different writing complexity (number of strokes), and the effect of motor imagery tasks of Chinese characters with different writing complexity on the performance of motor-imagery-based BCI is still unclear. In this paper, a total of 12 healthy subjects were recruited for studying the effects of motor imagery tasks of Chinese characters with two different writing complexity (5 and 10 strokes) on the performance of motor-imagery-based BCI. The experimental results showed that, compared with Chinese characters with 5 strokes, motor imagery task of Chinese characters writing with 10 strokes obtained stronger sensorimotor rhythm and better recognition performance (
Brain-Computer Interfaces ; China ; Electroencephalography ; Evoked Potentials ; Humans ; Imagery, Psychotherapy ; Imagination

ObjectiveTo observe the effects of Hirudo， Notoginseng Radix et Rhizoma， and drug pair on renal pathological morphology and protein phosphatase 2A （PP2A）/adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signal pathway in rats with chronic renal failure （CRF）. MethodThe 55 male SD rats were randomly divided into a normal group （n=11） and a modeling group （n=44）. The normal group was fed conventionally， and the modeling group was given 0.25 g·kg^-1·d^-1 adenine by gavage for 28 days to replicate the CRF model. After successful modeling， rats were randomly divided into model group， Hirudo group （3 g·kg^-1·d^-1）， Notoginseng Radix et Rhizoma group （3 g·kg^-1·d^-1）， and Hirudo + Notoginseng Radix et Rhizoma group （3 g·kg^-1·d^-1）， with 9 rats in each group. The normal group and model group were given a constant volume of normal saline by intragastric administration for 30 days. At the end of the experiment， the levels of serum creatinine （SCr） and urea nitrogen （BUN） in all groups were measured. The renal pathological morphology changes were observed by hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy. The mRNA expressions of PP2A， AMPK， and mTOR were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of PP2A， AMPK， phosphorylation（p）-AMPK， mTOR， and p-mTOR in renal tissue were detected by Western blot. ResultCompared with the normal group， the renal pathological structure changes were obvious， and the levels of SCr and BUN were significantly increased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression were significantly increased， and the p-AMPK/AMPK was significantly decreased in the model group （P<0.05）. Compared with the model group， the renal pathological morphology changes were significantly improved， and the levels of SCr and BUN were significantly decreased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression in the renal tissue were significantly decreased， and the p-AMPK/AMPK was significantly increased （P<0.05） in all groups after drug intervention. In addition， the effect in the Hirudo+Notoginseng Radix et Rhizoma group was better. The mRNA expression levels of AMPK and mTOR in the renal tissue were not significantly different among the normal group， model group， and other groups. ConclusionThe efficacy of Hirudo and Notoginseng Radix et Rhizoma pairs in improving renal fibrosis in rats with CRF is significantly better than that of the single drug， and its improvement on renal fibrosis in rats with CRF may be related to the regulation of PP2A/AMPK/mTOR signaling pathway.

In recent years, antisense oligonucleotide (ASO) has been very active in the field of rare disease research and development, especially in Duchenne muscular dystrophy, where it made a major breakthrough. Duchenne muscular dystrophy (DMD) is a rare childhood myopathy caused by mutations in the dystrophin gene. Currently, the four ASO drugs approved internationally for DMD are all targeted at dystrophin, including eteplirsen, golodirsen, viltolarsen and casimersen. They all belong to phosphorodiamidate morpholino oligomers (PMO) antisense oligonucleotide drugs, so that their pharmacokinetic characteristics are similar. The drugs quickly spread to other tissues after intravenous administration. Because of the electrical neutrality of the PMO, they have a low binding rate to plasma proteins and are quickly metabolized by the kidney and excreted in the urine as archetypes. In addition, the likelihood of drug-drug interactions of ASO is low. Existing clinical studies have shown that they have certain clinical benefits and good tolerability, bringing new options for DMD treatment. This paper mainly discusses the pharmacological effects, pharmacokinetic characteristics, efficacy, and safety of ASO drugs for the treatment of DMD, hoping to provide scientific reference for the rational and safe clinical use of such drugs.