Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction （强心汤） for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database， and the targets of chronic heart failure were screened by searching GeneCards， OMIM， TTD， PharmGkb， and DrugBank databases， and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network （PPI）， Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets， and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction， among which the core targets were estrogen receptor 1 （ESR1， degree value=7）， nuclear receptor coactivator 1 （NCOA1， degree value=8）， glucocorticoid receptor （NR3C1， degree value=7）， and nuclear receptor coactivator 2 （NCOA2， degree value=7）. GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity， postsynaptic neurotransmitter receptor activity， and neurotransmitter receptor activity （P＜0.01）； the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway， adrenergic receptor signaling pathway， and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway （P＜0.01）； the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane， synaptic membrane， and presynaptic membrane （P＜0.01）. KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， cocaine addiction， and cyclic guanosine monophosphate-protein kinase G （cGMP-PKG） signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets （ESR1， NCOA1， NR3C1， NCOA2）. ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， chemoattractant-receptor activation， cGMP-PKG signaling pathway， lipids and atherosclerosis， and cAMP signaling pathway， and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.

Objective:To analyze the changes of thyroid volume before and after supplementation with lipiodol pills in children with goiter, and to evaluate the recovery effect of lipiodol pills supplementation on children with goiter in the short term.Methods:In October 2018, 4 townships and towns in Linxia Hui Autonomous Prefecture with relatively serious historical conditions and high goiter rate of children aged 8 to 10 were selected for thyroid examination in 19 primary schools within the jurisdiction. Sixty children with goiter were selected as research subjects; at the same time, 138 children of the same age with normal thyroid B-ultrasound examination results were selected as control in the same period. Under the condition of normal diet, children with goiter were intervened by taking 200 mg lipiodol pills at one time. After 6 months, the thyroid volume of children with goiter and control children was measured by B-ultrasound.Results:Fifty-three children with goiter were finally included, with a sex ratio of 1.00 ∶ 1.04 (26 ∶ 27). There were 138 control children in the same period, with a sex ratio of 1.00 ∶ 1.30 (60 ∶ 78). Six months after taking lipiodol pills, the median thyroid volume of children with goiter was 3.7 ml, which was significantly different from that before supplementing with lipidol pills (5.8 ml, Z = - 7.95, P < 0.001), and not significantly different from that of control children (4.1 ml) in the same period ( Z = - 0.91, P = 0.365). Among them, 90.6% (48/53) of children with goiter recovered to the normal range, and 100.0% (15/15), 81.8% (18/22) and 93.8% (15/16) children's thyroid recovered returned to the normal range in the 8-, 9-, and 10-year-old age groups, respectively, and the highest proportion was in the 8-year-old age group. Stratified by age and gender, the thyroid volume of children with goiter in all age groups and gender after supplementation with lipiodol pills was lower than that before supplementation with lipiodol pills ( P < 0.001), but there was no difference compared with the control children in the same period ( P > 0.05). After supplementing with lipiodol pills, the diameters of thyroid in children with goiter were significantly lower than those before supplementing with lipiodol pills ( P < 0.001). Compared with the control children in the same period, there were significant differences in the right width, left length and right long diameter of the thyroid ( P < 0.05). Conclusion:Supplementing lipiodol pills can restore the thyroid volume of 8 - 10 year old children with goiter to normal range in a short term, and can effectively treat simple goiter.

Objective:To explore the performance of the attention-multiple instance learning (MIL) framework, an attention fusion network-based MIL, in the automated diagnosis of chronic gastritis with multiple indicators.Methods:A total of 1 015 biopsy cases of gastritis diagnosed in Fudan University Cancer Hospital, Shanghai, China and 115 biopsy cases of gastritis diagnosed in Shanghai Pudong Hospital, Shanghai, China were collected from January 1st to December 31st in 2018. All pathological sections were digitally converted into whole slide imaging (WSI). The WSI label was based on the corresponding pathological report, including "activity" "atrophy" and "intestinal metaplasia". The WSI were divided into a training set, a single test set, a mixed test set and an independent test set. The accuracy of automated diagnosis for the Attention-MIL model was validated in three test sets.Results:The area under receive-operator curve (AUC) values of Attention-MIL model in single test sets of 240 WSI were: activity 0.98, atrophy 0.89, and intestinal metaplasia 0.98; the average accuracy of the three indicators was 94.2%. The AUC values in mixed test sets of 117 WSI were: activity 0.95, atrophy 0.86, and intestinal metaplasia 0.94; the average accuracy of the three indicators was 88.3%. The AUC values in independent test sets of 115 WSI were: activity 0.93, atrophy 0.84, and intestinal metaplasia 0.90; the average accuracy of the three indicators was 85.5%.Conclusions:To assist in pathological diagnosis of chronic gastritis, the diagnostic accuracy of Attention-MIL model is very close to that of pathologists. Thus, it is suitable for practical application of artificial intelligence technology.

Purpose: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). Conclusion RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

Objective:To observe the expressions of SENP1, SENP2and SENP6proteins in human malignant glioma tissue and cells, and to elucidate the their effects in the development of malignant glioma.Methods:The samples of normal human brain tissue and malignant glioma tissue were obtained and used as normal control group and malignant glioma group, respectively.The Cos7cells and the malignant glioma LN443and U343cells were cultured;the Cos7cells were used as normal cell control group, and the LN443and U343cells as malignant glioma cell group.Western blotting method was used to detect the expression levels of SENP1, SENP2and SENP6proteins in human malignant glioma tissue and cells.Results:In brain tissue, the expression levels of SENP1, SENP2and SENP6proteins in malignant glioma group were higher than those in normal control group (P＜0.05) .Compared with normal cell control group, the expression levels of SENP1, SENP2and SENP6proteins in the LN443and U343cells in malignant glioma cell group were significantly increased (P＜0.05) .Conclusion:SENP1, SENP2and SENP6proteins highly express in the malignant glioma tissue and cells, and they may play an important role in promoting the occurrence of malignant glioma.

OBJECTIVE:To provide reference for variety breeding,high yield and high quality cultivation of Momordica cochi-nchinensis. METHODS:Based on Chinese Pharmacopoeia (2015 edition,Vol Ⅰ),HPLC for determining the content of gyp-sogenin 3-O-β-D-glucuronic acid methyl ester in M. cochinchinensis was optimized,the contents of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochinchinensis from 14 production places of 8 provinces were compared,and cluster analysis was conduct-ed. Correlation of longitude,latitude and altitude with content of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochinchi-nensis was analyzed by SPSS17.0 software. RESULTS:Gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochinchinensis showed good linear relationship in 0.05-0.5 mg/mL,regression equation was Y=4361.95X+67.3808(R2=0.9997);the limits of quantification and detection were 15.62 ng and 4.67 ng,respectively. Average recovery was 99.76%(RSD=1.36%,n=9). The content of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochinchinensis from 14 production places of 8 provinces had ex-tremely significant differences(P<0.01). Clustering analysis results indicated that M. cochinchinensis from 14 production places of 8 provinces were divided into Ⅰ,Ⅱ,Ⅲ,Ⅳ groups. Contents of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochi-nchinensis of Ⅲ,Ⅳ groups were relatively high,including Guangxi Pingnan,Guizhou Jiangkou,Guizhou Dejiang,Fujian Jian-yang and Hunan Huitong,in which,Guangxi Pingnan,Guizhou Jiangkou,Guizhou Dejiang and Hunan Huitong had high altitude and low latitude,Fujian Jianyang had high altitude. The content of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochi-nchinensis was positively correlated with altitude,while negatively correlated with longitude and latitude. CONCLUSIONS:HPLC is simple,accurate and reproducible for determining the content of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochi-nchinensis,and the determined contents of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochinchinensis from 14 produc-tion places of 8 provinces have reached the standard of Chinese Pharmacopoeia (2015 edition,Vol Ⅰ). Cultivation in Guangxi Pingnan,Guizhou Jiangkou,Guizhou Dejiang,Hunan Huitong and other areas with high altitude and low latitude helps to improve the content accumulation of gypsogenin 3-O-β-D-glucuronic acid methyl ester in M. cochinchinensis.

Objective Promote the use of medical record information, the depth of excavation,provide strong support for clinical research and hospital management.Methods Medical Record Information lower utilization reasons put forward need to build the whole structure of the paperless electronic medical records, electronic medical records for research concluded that the key to building elements to provide support.Results Pointed out that the construction of paperless electronic medical records from the storage structure of the building medical record systems, and data warehouse technology combined start, outpatient and inpatient medical records while achieving interoperability, building regional health care, improve follow-up system, and finally pointed out the key technical implementation.Conclusions It is to promote the utilization of medical records, medical records for research to improve support efforts to promote development and progress of medicine and enhance the hospital's soft power has great significance.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cell Culture Techniques ; methods ; Child ; Female ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Male ; Middle Aged

Objective To review the outcomes of three different methods of maxillomandibular advancement for the treatment of severe obstructive sleep apnea-hypopnea syndrome(OSAHS).Methods Twenty-four patients with severe OSAHS from January 2011 to January 2014 treated by three different methods of maxillomandibular advancement(MMA) and genioplasty,maxillomandibular advancement without rotation plus genioplasty,maxillomandibular advancement with counterclockwise rotation plus advancement genioplasty,maxillomandibular advancement with first premolars extraction and subapical osteotomy setback under general anesthesia were included in the study.Comparison of per-operative and post-operative cephalometric analysis,polysomnography(PSG),apnea and hypopea index(AHI),body mass index(BMI),average blood oxygen saturation(AOS),lowest oxygen saturation(LSaO2) and posterior airway space(PAS) data were performed.The operative time and post-surgical orthodontic treatment data were collected and analyzed.Results According to Stanford criteria,the success rate of 100％ was achieved with all the three methods.The difference between per-operative and post-operative AHI,AOS,SNPg and PAS were statistically significant(P＜0.000 1) for all the three methods.Significant difference was found between per-operative and post-operative SNA(81.51 °±3.36° vs 88.17°±4.51 °,P＜0.000 1),(82.25°±2.71 ° vs 86.54°±3.65°,P=0.000 2) and SNB(72.37°±3.99° vs 80.59°±3.40°,P＜0.000 1),(73.65°±3.80° vs 81.37°±2.96°,P＜0.000 1) among MMA without rotation plus genioplasty and MMA with counterclockwise rotation and advancement genioplasty respectively.However,no significant difference was found between the pre-operative and post-operative SNA(82.18°±4.27° vs 84.19°±2.70°,P=0.201 5) and SNB(73.28°±3.04° vs 75.35°±2.56°,P=0.264 0) among MMA with first premolars extraction and subapical osteotomy setback.The average duration of postoperative orthodontics treatment was 8.3 months.Conclusions MMA and advancement genioplasty is an effective surgical management for severe OSAHS.Cephalometric analysis and computer aided design are needed for personalized surgical methods.MMA without rotation and advancement genioplasty method leads to the protrusive skeletal deformity.MMA with counterclockwise rotation and advancement genioplasty method is effective in curing severe OSAHS with little effect on facial profile.MMA with first premolars extraction and subapical osteotomy requires longer operative time and longer postoperative orthodontic treatment.