[Evaluation of brain age changes in patients with liver cirrhosis and hepatic encephalopathy with deep learning models based on structural magnetic resonance imaging].

Objective: To investigate the brain aging in patients with cirrhosis and hepatic encephalopathy(HE), constructed a prediction model of brain age based on deep learning and T1 high-resolution MRI, and try to reveal the specific regions where cirrhosis and HE accelerating brain aging. Methods: A cross-sectional study. A brain age prediction model based on the 3D full convolutional neural network was constructed through T1 high-resolution MRI data from 3 609 healthy individuals across eight global public datasets. The mean absolute error (MAE) between actual age and predicted brain age, Pearson correlation coefficient (r) and determination coefficient (R2) were calculated to evaluate the accuracy of the model's predictions. A test set (n=555) from the Human Connectome Project was used to assess the accuracy of the model. A total of 136 patients with cirrhosis were recruited from Tianjin First Central Hospital as the case group (79 patients with cirrhosis without HE and 57 patients with cirrhosis with HE), and 70 healthy individuals were recruited from the society as the healthy control group during the same period. Brain-predicted age difference (Brain-PAD), digital connection-A (NCT-A) and digital-symbol test (DST) scores of all subjects were calculated for all subjects to assess brain aging and cognitive function in the healthy control group, the cirrhosis without HE group, and the cirrhosis with HE group. The network occlusion sensitivity analysis method was employed to assess the importance of each brain region in predicting brain age. Results: As for the prediction model, in the training set, MAE=2.85, r=0.98, R2=0.96. In the test set, MAE=4.45, r=0.96, R2=0.92. In the local data set of the healthy control group, MAE=3.77, r=0.85, R2=0.73. The time of NCT-A in both cirrhosis groups was longer than healthy control group, while the DST scores were lower than healthy control group, and the differences were statistically significant (both P<0.001); the Brain-PAD of healthy control group was (0.8±4.5) years, the Brain-PAD of no-HE group was (6.9±8.1) years, and the HE group was (10.2±7.7) years. The differences between the three groups were statistically significant (P<0.001), and the differences between any two groups were statistically significant (all P<0.05). The importance ratio of visual network in predicting brain age increased in cirrhosis patients, and the HE group was higher than no-HE group. Conclusions: In patients with cirrhosis, the cognitive function is reduced, brain aging is accelerated, and these changes are more obvious in patients with HE. The importance differences of each brain network in predicting brain aging provide a new direction for identifying the specific regions where cirrhosis and HE accelerate brain aging.

[Safety and efficacy of transcatheter aortic valve replacement using the "All in One" single artery/vessel technique].

Objective: To explore the safety and efficacy of transcatheter aortic valve replacement (TAVR) using the "All in One" single-artery/vessel technique. Methods: This is a retrospective study. A total of 30 consecutive patients underwent TAVR using the single artery/vascular technique in Beijing Anzhen Hospital from August to December 2021 were included. Baseline clinical data, operative situation, postoperative outcomes, and incidence of adverse events during hospitalization and at one month post TAVR were analyzed. Results: Mean age was (72.6±9.7) years, 16 were male patients, STS score was (4.73±3.12)%. Four patients were diagnosed as isolated aortic regurgitation (all with tricuspid aortic valves), and 26 patients were diagnosed as aortic stenosis (AS), 10 of whom with tricuspid aortic valves and 16 of whom with bicuspid aortic valves. The single-vessel technique was applied in 3 aortic stenosis cases; the single-artery technique was applied in 27 cases. Echocardiography was performed immediately after procedure and results showed no or trace perivalvular leak in 27 cases and small perivalvular leak in 3 cases; the mean aortic transvalvular gradient of 26 AS patients decreased from (50.4±16.0) mmHg (1 mmHg=0.133 kPa) to (9.4±3.2) mmHg (P<0.001). The procedure time was (64.8±18.9) min. There were no intraoperative death, valve displacement, conversion to surgery, coronary artery occlusion in all 30 patients. There were no major cardiac adverse events such as myocardial infarction or stroke occurred during hospitalization or at follow-up. One-month follow-up echocardiography indicated prosthesis works well. The symptoms were significantly alleviated, and the Kansas City Cardiomyopathy Score (KCCQ score) of all patients increased from 48.1±18.4 to 73.5±17.6 (P<0.001). Conclusions: TAVR using the single artery/vessel technique is safe and feasible. This technique is related to reduced access complications and worthy of wide application.

[Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR].

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

[Expression of glycolytic genes in immune cells and changes of related immune cells in experimental autoimmune neuritis].

Objective: To investigate the expression of glycolytic genes in immune cells and the changes of related immune cells in experimental autoimmune neuritis (EAN), and deepen the understanding of pathogenesis of EAN. Methods: Twenty-four male C57BL/6 mice (6-8 weeks old, 18-20 g) were divided into four groups according to the random number table method: control group (P0180-199 was replaced by PBS during modeling and mice were sacrificed on the 16th day), EAN mice were sacrificed on the 8th day after the end of modeling (EAN 8 d), EAN mice were sacrificed on the 16th day after the end of modeling (EAN 16 d), and EAN mice received drug intervention and were sacrificed on the 16th day after the end of modeling (2-DG was intraperitoneally injected since the day of the first immunization, 550 mg/kg; EAN 16 d+2-DG), with 6 rats in each group. The clinical symptoms and clinical scores were observed and recorded daily. At the end of the experiment, the mice were sacrificed under chloral hydrate anesthesia, and the serum, spleen, sciatic nerve and other tissues of each group were collected. The degree of inflammatory cell infiltration and demyelination of sciatic nerve were observed by hematoxylin and eosin (HE) staining and luxol fast blue (LFB) staining. Flow cytometry was used to detect the proportion of M1 macrophages, Th17 cells and Tregs cells. The mRNA expression levels of glycolysis-related genes (mTORC1, HIF1α, GLUT1 and LDHA) were detected by RT-PCR. Western blotting was used to detect the level of pan-lysine lactate in macrophages and sciatic nerve tissue. Results: The expression of glycolysis-related genes (mTORC1, HIF1α, GLUT1 and LDHA) in spleen M1 macrophages and sciatic nerve was significantly up-regulated in EAN 16 d group, compared with control, EAN 8 d and EAN 16 d+2-DG groups (all P<0.05). The relative pan-lysine lactate (pankla) expression level of spleen M1 macrophages (1.25±0.02) and sciatic nerve tissue (1.23±0.26) significantly increased in EAN 16 d group, compared with control, EAN 8 d and EAN 16 d+2-DG groups (M1 macrophages: 0.12±0.10, 1.07±0.12 and 0.42±0.07; sciatic nerve: 0.10±0.12, 0.87±0.20 and 0.36±0.05) (all P<0.05). The expression of glycolytic genes in splenic CD4+T cells showed an increasing trend, but there were no statistically significant differences among the groups, and the expression of glycolytic genes did not decrease significantly after 2-DG treatment (all P>0.05). The proportion of spleen M1 macrophages in the control group, EAN 8 d group, EAN 16 d group and EAN 16 d+2-DG group was 4.28±0.13, 7.54±0.25, 13.16±0.33 and 4.13±0.38 respectively, which was significantly higher in the EAN 16 d group (all P<0.05). The proportion of spleen Th17 cells in the four groups was 3.78±0.03, 8.24±0.55, 12.30±1.34 and 4.83±0.01, respectively, which was significantly higher in the EAN 16 d group (all P<0.05). The proportion of spleen Tregs cells in the four groups was 10.01±1.05, 7.54±0.70, 3.82±0.47 and 8.22±1.21, respectively, which was significantly lower in the EAN 16 d group (all P<0.05). Conclusions: The expression of glycolytic genes in splenic macrophages significantly increases during EAN, but not in CD4+T cells. The proportion of M1 macrophages and Th17 cells in spleen gradually increases, while the proportion of Tregs cells gradually decreases.

[Effects of adjuvant trastuzumab on long-term survival of T1N0M0 stage human epidermal growth factor receptor 2 positive breast cancer: a real-world study].

Objective: To investigate the prognosis impact of adjuvant trastuzumab treatment on human epidermal growth factor receptor 2 (HER-2) positive early breast cancer patients. Methods: A retrospective study was conducted, HER-2-positive T1N0M0 stage breast cancer patients who underwent surgery in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2010 to December 2019 were divided into treatment group and control group according to whether they were treated with trastuzumab or not. Propensity score matching (PSM) was used to balance the confounding bias caused by differences in baseline characteristics between the two groups. Cox proportional hazards model was used to analyze the risk factors affecting disease-free survival (DFS). The Kaplan-Meier method was used to estimate the 3- and 5-year DFS and overall survival (OS) rates of the two groups before and after PSM. Results: There were 291 patients with HER-2 positive T1N0M0 stage breast cancer, including 21 cases in T1a (7.2%), 61 cases in T1b (21.0%), and 209 cases in T1c (71.8%). Before PSM, there were 132 cases in the treatment group and 159 cases in the control group, the 5-year DFS rate was 88.5%, and the 5-year OS rate was 91.5%. After PSM, there were 103 cases in the treatment group and 103 cases in the control group, the 5-year DFS rate was 86.0%, and the 5-year OS rate was 88.5%. Before PSM, there were significant differences in tumor size, histological grade, vascular invasion, Ki-67 index, postoperative chemotherapy or not and radiotherapy between the treatment group and the control group (P<0.05). After PSM, there were no significant difference in clinicopathological features between the treatment group and the control group (P>0.05). Multivariate analysis showed that histological grade (HR=2.927, 95 CI: 1.476, 5.805; P=0.002), vascular invasion (HR=3.410, 95 CI: 1.170, 9.940; P=0.025), menstrual status (HR=3.692, 95 CI: 1.021, 13.344, P=0.046), and chemotherapy (HR=0.238, 95 CI: 0.079, 0.720; P=0.011) were independent factors affecting DFS. After PSM, the 5-year DFS rate of the treatment group was 89.2%, while that of the control group was 83.5%(P=0.237). The 5-year OS rate of the treatment group was 96.1%, while that of the control group was 84.7%(P=0.036). Conclusion: Postoperative targeted therapy with trastuzumab can reduce the risk of recurrence and metastasis in patients with HER-2-positive T1N0M0 stage breast cancer.

[Single center experience of transcatheter aortic valve replacement with a simplified operative protocol].

Objective: To summarize the single center experience of transcatheter aortic valve replacement (TAVR) with a simplified operative protocol. Methods: Consecutive patients who underwent transfemoral TAVR (TF-TAVR) from July 2020 to December 2020 in Fuwai Hospital were retrospectively analyzed. We compared the baseline characteristic, procedure information, 30-day follow-up outcomes of the patients who underwent TF-TAVR without the simplified operative protocol (routine group) or with the simplified operative protocol (simplified protocol group). Results: 93 patients were collected, 42 patients belonging to routine group, 51 patients belonging to simplified protocol group. In simplified protocol group, there were 51 patients planned to use ultrasound-guided femoral access puncture, procedure was successful in all 51 patients (100%). There were 49 patients planned to use the radial artery as the secondary access, procedure was successful in 45 patients (92%). There were 48 patients planned to use the strategy of avoidance of urinary catheter, this strategy was achieved in 35 patients (73%). There were 12 patients planned to use the left ventricular guidewire to pace, procedure was successful in 11 patients (92%). There were no differences in baseline characteristics, major clinical endpoints and 30-day follow-up outcomes between the two groups. Meanwhile, the procedure time ((62.5±17.9)min vs. (78.3±16.7)min, P<0.001), operation room time ((133.7±25.1)min vs. (159.2±42.6)min, P<0.001), X-ray exposure time ((17.2±6.5)min vs. (20.2±7.7)min, P=0.027) were significantly shorten in simplified protocol group compared with the routine group. Conclusion: Our study results indicate that the simplified operative protocol of TF-TAVR is as effective and safe as the routine operative protocol, meanwhile using the simplified operative protocol can significantly increase the operative efficiency of TF-TAVR.

A clinical investigation into the usefulness of fractional exhaled nitric oxide in guiding glucocorticoid therapy in children with bronchial asthma.

The present study aims to investigate the value of fractional exhaled nitric oxide (FeNO) combined with pulmonary function in guiding the dose adjustment of inhaled glucocorticosteroids (ICSs) in children with asthma. A total of 133 children aged 6-12 years with newly diagnosed asthma were enrolled as the study subjects and randomly divided into the experimental group (n=68) and the control group (n=65). After three months of ICS treatment, in the experimental group, the dose of ICSs was adjusted based on the control status of the children and the results of the pulmonary function tests and FeNO assays, and in the control group, the dose was adjusted based on the control status of the children and the results of the pulmonary function tests. After another three months of treatment, the number of acute asthma attacks and the Childhood Asthma Control Test (C-ACT) scores were compared between the two groups, and the outcome of pulmonary function tests and FeNO assays during treatment were analyzed. When examining pulmonary function and FeNO levels, when compared with before treatment, there were no statistically significant differences in either group or between the groups after three months of ICS treatment (P>0.05). After dose adjustment and another three months of treatment, when compared with the control group, the improvement in pulmonary function in the experimental group was greater, the reduction in FeNO levels was greater, the incidence of acute asthma attacks was lower, and the C-ACT score was higher (P<0.05). We concluded that the combination of FeNO assays and pulmonary function tests to guide the ICS dose adjustment in children with asthma could improve asthma control and reduce the risk of acute asthma attacks.

[Cognitive function analysis of chronic lead poisoning in adults].

Objective: To explore the changes of the auditory event-related potentials P300 and the Montreal Cognitive Assessment (MoCA) in the chronic mild lead poisoning in order to find out the impairment of cognitive function and intervene early. Methods: In February 2020, 50 patients with chronic mild lead poisoning in Wuhan Center for Prevention and Treatment of Occupational Diseases from June 2011 to June 2015 were selected as the case group, and 50 healthy people were selected as the control group. The changes of auditory event-related potential P300 and MOCA of the two groups were analyzed. Results: Compared with the control group, the latency of P300 of auditory event-related potential in the case group was prolonged and the amplitude was decreased (P<0.05) . Compared with the control group, the total score of MoCA in the case group was decreased, the mean score of language, abstract and delayed memory items decreased, and the differences were statistically significant (P<0.05) . Conclusion: The combination of auditory event-related potential P300 and MOCA is helpful to detect the early cognitive impairment in chronic lead poisoning population, and auditory event-related potential P300 is an objective and effective early detection method.

The neutrophil to lymphocyte ratio as a novel predictor of asthma and its exacerbation: a systematic review and meta-analysis.

OBJECTIVE: It is widely known that the main white blood cell populations, and neutrophil to lymphocyte ratio (NLR), are involved in systemic inflammation. The usefulness of NLR measurements has been reported in patients with asthma. We performed a systematic review and meta-analysis of studies to investigate the relationship between the NLR and asthma and its exacerbations. MATERIALS AND METHODS: We systematically searched PubMed and Embase databases for studies (published between Jan 1, 1950 and Jan 2, 2020; no language restrictions) comparing the NLR values in patients with stable asthma or asthma exacerbations to healthy controls. We assessed pooled data by use of a random-effects model. RESULTS: Of 260 identified studies, 6 were eligible and were included in our analysis (N = 2418 participants). Compared with 439 healthy controls, 743 stable asthma patients in four studies showed significantly greater NLR values (standardized mean difference, SMD, 0.567, 95% CI 0.212-0.922; p = 0.002). Furthermore, compared with 1063 stable asthma patients, 402 asthma exacerbation patients yielded significantly greater NLR values (random effects SMD 1.335, 95% CI 0.429-2.241; p < 0.001). CONCLUSIONS: Our meta-analysis showed that the NLR values are a reasonable and easy-to-use marker for asthma and its exacerbations. Further studies, with larger sample sizes and more phenotypes, are required to establish its use as a predictive parameter in asthma.

[Analysis of differences in epidemiology and clinical features of Guillain-Barré syndrome between rural and urban areas of southern China].

Objective: To explore the differences in epidemiology and clinical features of Guillain- Barré syndrome (GBS) between rural and urban areas of southern China. Methods: The clinical data of 759 hospitalized GBS patients from 31 hospitals of 13 provinces/cities in southern China, between January 1st, 2013 and September 30th, 2016, were collected and analyzed retrospectively. Results: The risk of GBS was higher for males than females in rural and urban areas and the median age was 49 and 48 years, respectively. Seasonal clustering in winter and spring was noted in both rural and urban areas, and the seasonal trend was more markedly in rural areas, but the differences showed no statistical significance. There were 70.37% of patients in rural areas and 73.69% in urban areas who had antecedent respiratory infection. The median time from onset to nadir was 7 days, and Hughes Disability Scale at admission, nadir and discharge were (2.95±1.10 vs 2.84±1.15), (3.25±1.11 vs 3.14±1.21), (2.02±1.24 vs 2.00±1.31) in rural and urban areas respectively. Albuminocytologic dissociation was present in 84.34% of patients in rural areas and 84.62% of cases in urban areas. There were 8.65% and 10.94% of cases in rural and urban areas who required mechanical ventilation during hospitalization, respectively. Demyelinating GBS accounted for 53.29% and 48.77%, respectively, in patients with findings of nerve conduction studies available in rural and urban areas. Conclusions: GBS in rural areas of southern China showed male predominance and a peak of spring and winter occurrence, with respiratory infection as the predominated preceding events and demyelinating GBS being main clinical subtype. Winter and spring showed a higher incidence of GBS in rural and urban areas. There were no significant differences of sex, age, preceding events, season trend, progression of disease, clinical subtypes and cerebrospinal fluid investigations in GBS patients between rural and urban areas.

[Genes polymorphism of BIN1 and ApoE in patients with amnestic mild cognitive impairment from Enshi Tujia area].

Objective: To investigate the polymorphism of BIN1 and ApoE genes in amnestic mild cognitive impairment (aMCI) patients in Tujia minority area of Enshi, Hubei. Methods: A total of 107 patients with aMCI (aMCI group) and 150 healthy people (healthy control group) during the same period were included between December 2016 and October 2017 in Affiliated Minda Hospital of Hubei University for Nationalities, who were all the Tujia nationality. Three single nucleotide polymorphic site of BIN1 gene rs744373, rs7561528, rs6733839, and two single nucleotide polymorphic site of ApoE gene rs429358, rs7412, and Genotyping and sub-genotyping of ApoE genes were tested using ligase detection reaction technique(LDR), and gene polymorphisms of BIN1 and ApoE were analyzed with Logistic regression analysis. Results: The basic information was not statistically significan different between healthy control group and aMCI group (P>0.05); there were no statistically significant in genotype distribution among the 3 SNPs of BIN1 gene(rs744373, rs7561528, rs6733839) and between the 2 SNPs of ApoE gene(rs429358, rs7412) and its allelic profile (P>0.05), which conformed to Hardy-Weinberg balance; BIN1 gene rs744373 polymorphic site allele C was the risk factor of aMCI (OR 2.33, 95% CI 1.09-4.98, P=0.029), especially BIN1 gene rs744373 polymorphic site recessive model CC/CT+ TT increased the risk of aMCI disease (OR 2.29, 95% CI 1.15-4.59, P=0.019). The difference in genotype distribution of ApoE sub-genotype ε2/2, ε2/3, ε2/4, ε3/3, ε3/4, ε4/4 and allele ε2, ε3, ε4 genes between two groups were significantly different (P<0.05), Carrying ApoEε2 may be a protective factor for aMCI (OR 0.46, 95% CI 0.22-0.96, P=0.039) and carrying ApoE ε4 may be a risk factor for aMCI (OR 2.13, 95% CI 1.18-3.83, P=0.012). Conclusions: The incidence of aMCI in Tujia region of Enshi may be related to the rs744373 polymorphic site of BIN1 gene, ApoEε2 is the protective factor and ApoEε4 is the risk factor for aMCI in Tujia region of Enshi, but it still needs to be further verified by a large sample population.

[A preliminary study on the clinical characteristics of Parkinson's disease patients with restless legs syndrome].

Objective: To study the clinical characteristics of Parkinson's disease (PD) patients with restless legs syndrome (RLS). Methods: Ninety-nine PD patients and eighty-nine control group were included into this study and assessed for RLS by the question 6 of the non-motor symptoms questionnaire (NMSquest). The PD patients were divided into the RLS group and non RLS group, according to their answers to the NMSquest.The severity of motor symptoms, anxiety, depression and quality of life were evaluated according Unified Parkinson Disease Rating Scale (UPDRS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Parkinson' s Disease Quality Of Life Questionnaire(PDQ-39), respectively. Results: (1)18.2%(18/81)of the PD patients experienced RLS, the incidence was significantly higher than the general population (P<0.001). (2) The RLS patients were more often women (66.7% vs 33.3%, P=0.033 ). (3) The UPDRS-Ⅱ score(20±7, P=0.008), UPDRS-Ⅲ score(43±14, P=0.015), BDI score(23±13, P=0.002), BAI score(18±8, P=0.012), PDQ-39 score(75±26, P=0.000)in RLS group were significantly higher compared with non RLS group. (4) RLS showed no association with the course of the disease, the age, the PD onset age and levodopa dose equivalents. Conclusions: RLS more likely appears in PD patients, especially in women. The PD patients with RLS commonly suffer from serious motor symptom, low quality of life, anxiety and depression.

[Glabridin attenuates MPTP-induced parkinson disease by inhibiting extracellular regulated protein kinases signaling pathway].

Objective: To investigate whether Glabridin had a beneficial effect on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) induced parkinson disease (PD) in mice, and explore the possible underlying mechanisms. Methods: Forty C57BL/6N mice were randomly assigned into control group, MPTP group, Glabridin therapy(MPTP+ GLA)group, Levodopa therapy(MPTP+ LD)group, with 10 in each group. PD model was induced by intraperitoneal administration of MPTP(20 mg/kg). The mice in MPTP+ GLA group, MPTP+ LD group and control group were gavaged by glabridin (50 mg/kg), levodopa (40 mg/kg), and equal volume of normal saline, respectively. The behavioral changes of each group were observed and Y-type electric maze test was performed. The levels of tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were assayed by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA), and superoxide dismutase (SOD) were analyzed. The protein expression of tyrosine hydroxylase (TH) and extracellular signal regulated protein kinase (ERK) protein expression of hippocampus tissue was detected using immunohistochemical techniques. TH and pERK protein expression of hippocampus tissue were detected by Western blotting. Results: Mice in MPTP group showed typical behavior of PD, and the ability of learning and memory was significantly lower than those in the control group. Compared with MPTP group, the expressions of TNF-α and IL-18 were suppressed by GLA in hippocampus[TNF-α(µg/L): 84.04±18.66 vs 106.53±28.54; IL-18(µg/L): 42.34±6.01 vs 58.42±8.39]. The levels of MDA in hippocampus were down-regulated significantly in groups administrated with GLA[MDA(nmol/mgprot): 2.64±0.52vs 3.78±0.31], while the SOD level increased after GLA administration[SOD(U/mgprot): 93.45±9.59 vs 77.83±8.98]. The results of immunohistochemistry showed the expression of TH protein in MPTP group was significantly decreased compared with that in control group, while the p-ERK protein in MPTP group was significantly increased. In MPTP+ GLA group and MPTP+ LD group, the expression of TH protein was significantly higher than that in MPTP group, and the expression of p-ERK protein was significantly lower than that in MPTP group. Western blot results showed that compared with control group, the expression of TH was significantly decreased, and p-ERK protein in hippocampus was significantly higherin MPTP group. The expression of TH protein was significantly higher in MPTP+ GLA group than that in MPTP group, while the expression of p-ERK protein were inhibited by GLA in MPTP-induced PD mice. Conclusion: Traditional Chinese medicine glabridin can protect the learning and memory ability of PD mice induced by MPTP by inhibition of the ERK signal pathway, antioxidation and reduction of inflammation.

[Clinical efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism].

Objective: To assess the efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism. Methods: Ten consecutive patients with intermediate-risk acute pulmonary embolism who received thrombolytic treatment with reteplase at Thrombosis and Vascular Medicine Center, Fuwai Hospital from March to November in 2016 were included.Vital signs, right ventricular diameter, systolic pulmonary artery pressure, and biochemical markers were assessed before and after thrombolytic therapy with reteplase, and bleeding complications were also observed during 3 months follow up. Results: (1) For the efficacy outcomes: at 48 hours after thrombolytic treatment with reteplase, echocardiography-derived diameter of right ventricular was significant reduced from (27.9±3.8) mm to (24.8±2.6) mm (P=0.03), systolic pulmonary artery pressure decreased from (63.9±21.6) mmHg(1 mmHg=0.133 kPa) to (34.4±19.8) mmHg (P=0.02). Heart rate and breathing rate were also decreased significantly (both P<0.05), blood pressure remained unchanged post therapy.Hypoxemia was quickly corrected with an significant elevation of PaO(2) and SaO(2) ((65.2±14.3) mmHg vs. (80.0±9.6) mmHg, P=0.006; (90.8±3.5)% vs. (95.2 ±1.6)%, P=0.002 respectively). PaCO(2) was also increased significantly (P<0.05). Serum NT-proBNP and cTnI were decreased significantly (both P<0.05). There was no recurrent pulmonary embolism or deep-vein thrombosis during the 3 months follow-up. (2) For the safety outcomes: a thrombolytic relevant hemoptysis (about 70 ml) occurred in 1 patient, and was controlled by PCC therapy.No other clinically relevant events were observed during thrombolytic treatment. Eight patients were followed more than 3 months, there was no major bleeding complication or death during the follow up period. Conclusion: Treatment of intermediate-risk acute pulmonary embolism with reteplase is effective and safe and there are no obvious side effects.

Association between the polymorphisms in the ATP-binding cassette genes ABCB1 and ABCC2 and the risk of drug-resistant epilepsy in a Chinese Han population.

Epilepsy is a common disease of the nervous system; approximately 20-30% of all patients with epilepsy are reported resistant to antiepileptic drugs. ABCB1 and ABCC2 are members of ATP-binding cassette transporter (ABC) family that is involved in the excretion of antiepileptic drugs. In this case-control study, we have investigated the role of ABCB1 rs1045642 and rs2032582 and ABCC2 rs2273697 and rs717620 single nucleotide polymorphisms in antiepileptic drug-resistance in patients with epilepsy. A total of 254 patients with epilepsy (104 drug-resistant and 150 drug-responsive) were recruited from the People's Hospital of Wuhan University between March 2013 and April 2014. The correlation between the demographic, clinical, and genotypic characteristics of the patients and risk of drug resistance was statistically analyzed. Patients with drug-resistant epilepsy were more likely to present symptomatic epilepsy (χ2 = 22.29, P < 0.001) compared to those with drug-responsive epilepsy. The TT genotype of the ABCB1 rs717620 polymorphism was associated with a higher risk of drug-resistant epilepsy compared to the CC genotype [odds ratio (OR) = 2.97, 95% confidence interval (CI) = 1.11-8.29]. The TT genotype of ABCB1 rs717620 was also related with an increased risk of drug-resistant epilepsy (OR = 2.64, 95%CI = 1.03-7.13) compared to the CC+CT genotype in the recessive model. Thus, our study suggests that the ABCC2 rs717620 polymorphism is associated with resistance to antiepileptic drugs in Chinese patients with epilepsy.

Role of ADH1B rs1229984 and ALDH2 rs671 gene polymorphisms in the development of Alzheimer's disease.

In the present study, we investigated the association between ADH1B rs1229984 and ALDH2 rs671 polymorphisms and the development of Alzheimer's disease in a Chinese population. Genotyping of the ADH1B rs1229984 and ALDH2 rs671 polymorphisms was carried out by polymerase chain reaction-restriction fragment length polymorphism. Logistic regression analyses revealed that the AA genotype of ADH1B rs1229984 was associated with an increased risk of Alzheimer's disease (OR = 2.54, 95%CI = 1.19-5.41). In addition, ADH1B rs1229984 was also associated with elevated risk of Alzheimer's disease in both dominant (OR = 1.78, 95%CI = 1.09-2.93) and recessive (OR = 2.33, 95%CI = 1.18-4.57) models. For ALDH2 rs671, the AA genotype was correlated with an increased risk of Alzheimer's disease as compared to the GG genotype (OR = 4.57, 95%CI = 1.60-14.01). The ALDH2 rs671 polymorphism was associated with Alzheimer's in both dominant (OR = 1.79, 95%CI = 1.08-2.97) and recessive (OR = 4.17, 95%CI = 1.49-12.67) models. In conclusion, we observed that ADH1B rs1229984 and ALDH2 rs671 polymorphisms increased the risk of Alzheimer's disease in all the genetic models.

Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality.

Keratinocyte growth factor (KGF) stimulates the proliferation and differentiation of epithelial cells including those of the gastrointestinal tract. Although chemotherapeutics and radiation exposure kill rapidly proliferating tumor cells, rapidly dividing normal cells of the host's gastrointestinal tract are also frequently damaged, leading to the clinical condition broadly termed "mucositis." In this report, recombinant human KGF used as a pretreatment in several mouse models of chemotherapy and/or radiation-induced gastrointestinal injury significantly improved mouse survival. Using multiple-dose 5-fluorouracil, methotrexate, and radiation in combination and total body radiation alone models, KGF increased survival by 55% or greater. In the models that used chemotherapy with or without radiation, KGF significantly ameliorated weight loss after injury and accelerated weight gain during recovery. The basis of these systemic benefits appears to be due in part to the trophic effects of the growth factor on the intestinal epithelium because KGF pretreatment caused an increase in measures of mucosal thickness (villus height and crypt depth) that persisted during the course of 5-fluorouracil chemotherapy. Treatment with KGF also afforded a 3.5-fold improvement in crypt survival in the small intestine, suggesting that KGF also has a direct effect on the crypt stem cells. These data indicate that KGF may be therapeutically useful to lessen the intestinal side effects of current cancer therapy regimens.

Ovarian steroids and serotonin neural function.

The serotonin neural system originates from ten nuclei in the mid- and hindbrain regions. The cells of the rostral nuclei project to almost every area of the forebrain, including the hypothalamus, limbic regions, basal ganglia, thalamic nuclei, and cortex. The caudal nuclei project to the spinal cord and interact with numerous autonomic and sensory systems. This article reviews much of the available literature from basic research and relevant clinical research that indicates that ovarian steroid hormones, estrogens and progestins, affect the function of the serotonin neural system. Experimental results in nonhuman primates from this laboratory are contrasted with studies in rodents and humans. The sites of action of ovarian hormones on the serotonin neural system include effects within serotonin neurons as well as effects on serotonin afferent neurons and serotonin target neurons. Therefore, information on estrogen and progestin receptor-containing neurons was synthesized with information on serotonin afferent and efferent circuits. The ability of estrogens and progestins to alter the function of the serotonin neural system at various levels provides a cellular mechanism whereby ovarian hormones can impact mood, cognition, pain, and numerous other autonomic functions.

Somatosensory evoked potentials in patients with cerebral hemorrhage and infarct. Correlation with CT, clinical data and their prognostic significance on limb function.

Somatosensory evoked potentials (SEP) arising from median nerve stimulation were recorded in 102 patients with unilateral cerebral hemorrhage or infarct located in basal ganglion, internal capsule, thalamus or cerebral lobe. Of them 42 cases were followed up and reexamined with SEPs. Three types of SEPs were observed: 1) absence of all SEPs components, 39 cases; 2) slight to moderate abnormalities of SEPs, 37 cases; 3) symmetric and normal SEPs, 26 cases. The total abnormal rate of SEPs was 76.5%. There were no definite correlations between abnormal SEPs and lesion location, size and lesion nature. The diagnosis of cerebral vascular disease might be obtained more directly and precisely by CT scan than by SEPs. However, SEPs may serve as an objective neurophysiologic means in assessing the neurological function of the affected limb, in which their abnormalities and severity are of great value to evaluate the probability and the degree of sensorimotor functional rehabilitation of the limb. When SEPs are absent, the recovery of the limb functions may be very poor no matter whether it is hemorrhage or infarct regardless of its lesion size and location.