Study on mechanism of Yangxue Qingnao Granule for the treatment of vascular dementia disease based on network pharmacology and bioinformatics / 国际中医中药杂志

Objective:To explore the possible mechanism of Yangxue Qingnao Granule for the treatment of vascular dementia (VaD) based on network pharmacology and bioinformatics.Methods:The active components and potential targets of Yangxue Qingnao Granule in the treatment of VaD were obtained from TCMSP database, BATMAN-TCM database, GEO database and OMIM database, etc. The heatmap was visualized by using the pheatmap packages in R. Cytoscape 3.8.2 software and the CytoNCA plugin were utilized to build a network of "Chinese materia medica-active component-potential target". CytoNCA plug-in was used to analyze PPI network topology. Metascape was used for GO and KEGG pathway enrichment analyses. Finally, AutoDock Vina 1.5.6 software was applied to construct molecular docking between the active components and potential core targets. Resuls A total of 135 active components of Yangxue Qingnao Granule were screened and 186 potential targets of Yangxue Qingnao Granule against VaD were obtained. GO function enrichment analysis found protein kinase binding, transcription factor binding and other biological functions. KEGG pathway enrichment analysis identified PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, etc. Molecular docking showed that the main active components of Yangxue Qingnao Granule had good binding activity with the potential targets. Conclusion:Yangxue Qingnao Granule has the characteristics of multi-targets and multi- pathways in the treatment of VaD. It may play a therapeutic role in VaD by inhibiting neuronal apoptosis and reducing inflammatory response.

Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients / 中华胃肠外科杂志

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Effect of wheat-grain moxibustion on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition, and to explore the possible mechanism of wheat-grain moxibustion in treating bone marrow inhibition.@*METHODS@#Forty-five SPF male CD1(ICR) mice were randomly divided into a blank group, a model group and a wheat-grain moxibustion group, 15 mice in each group. The bone marrow inhibition model was established by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX). The mice in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), 3 moxa cones per acupoint, 30 s per moxa cone, once a day, for 7 consecutive days. The white blood cell count (WBC) was measured before modeling, before intervention and 3, 5 d and 7 d into intervention. After intervention, the general situation of mice was observed; the number of nucleated cells in bone marrow was detected; the serum levels of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were measured by ELISA; the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc in bone marrow cells was measured by Western blot and real-time PCR method.@*RESULTS@#Compared with the blank group, the mice in the model group showed sluggish reaction, unstable gait, decreased body weight, and the WBC, number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were decreased (P<0.01), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was decreased (P<0.01). Compared with the model group, the mice in the wheat-grain moxibustion group showed better general condition, and WBC, the number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were increased (P<0.01, P<0.05), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion shows therapeutic effect on bone marrow inhibition, and its mechanism may be related to activating Wnt/β-catenin signaling pathway in bone marrow cells, improving bone medullary hematopoiesis microenvironment and promoting bone marrow cell proliferation.

Analysis of clinicopathological features, gene mutation characteristics and prognosis of 228 cases of primary gastrointestinal stromal tumor of small intestine / 中华消化杂志

Objective:To analyze the clinicopathological features, gene mutation characteristics, and prognostic related factors of patients with primary gastrointestinal stromal tumor (GIST) of small intestine.Methods:From January 1, 2011 to December 30, 2019, surgical resected and pathological diagnosed small intestinal GIST without preoperative adjuvant therapy, at Tianjin Medical University Cancer Institute & Hospital were retrospectively collected. The mutational status of KIT exons 9, 11, 13, and 17 and platelet-derived growth factor receptor alpha ( PDGFRA) exons 12 and 18 were detected by polymerase chain reaction and Sanger direct sequencing. Clinicopathological features and gene mutation characteristics were analyzed. Pearson chi-square test and Bonferroni continuous correction test were used to compare the categorical variables among groups. Kaplan-Meier method and log-rank test were used for univariate survival analysis. The multivariate Cox proportional hazards regression model was used for multivariate survival analysis. Results:The proportions of patients with maximum tumor diameter> 10.0 cm and high-risk GIST located in the jejunum and ileum were higher than those of patients with primary GIST located in the duodenum (18.7%, 28/150 vs. 6.4%, 5/78; 56.7%, 85/150 vs. 43.6%, 34/78), and the differences were statistically significant ( χ2=14.67 and 12.46, P=0.002 and 0.006). The results of gene detection of 58 cases of small intestinal GIST indicated that the percentage of KIT gene mutant and wild type accounted for 84.5% (49/58) and 15.5% (9/58), among which 34 cases (69.4%), 12 cases (24.5%), 2 cases (4.1%) and 1 case (2.0%) were KIT gene exons 11, 9, 13 and 17 mutations, respectively, and none of the case with PDGFRA mutation. The 3-, 5-, and 10-year progression-free survival rates of the patients with small intestinal GIST were 88.1%, 85.0%, and 68.3%, respectively, and the 3-, 5-, and 10-year overall survival rates were 96.6%, 94.5%, and 86.1%, respectively. The results of univariate survival analysis showed that the progression-free survival rate and overall survival rate of patients with very low-risk and low-risk GIST were higher than those of patients with intermediate-risk and high-risk GIST (100.0%, 49/49 vs. 72.3%, 81/112; 100.0%, 49/49 vs. 89.3%, 100/112, respectively), and the differences were statistically significant ( χ2=14.07 and 4.92, P<0.001、=0.027). The results of univariate survival analysis of patients with intermediate-risk and high-risk GIST showed that the epithelioid cell type, mitotic index >5/5 mm 2, Ki-67 proliferation index >5%, and without postoperative adjuvant therapy were all related with progression-free survival time, and the differences were statistically significant ( χ2=8.39, 5.53, 13.73 and 15.44, P=0.004、0.019、<0.001、<0.001). Without postoperative adjuvant therapy was related with poor overall survival time ( χ2=7.06, P=0.008). The results of univariate analysis in patients with intermediate-risk and high-risk GIST and without postoperative adjuvant therapy showed that the epithelioid cell type, high-risk, mitotic index >5/5 mm 2 and Ki-67 proliferation index >10% were all related with progression-free survival time, and the differences were statistically significant ( χ2=10.08, 6.51, 10.37 and 15.72, P=0.001、0.011、0.001、<0.001). The results of multivariate analysis indicated that Ki-67 proliferation index >5% ( HR=5.018, 95% confidence interval(95% CI) 1.745 to 14.430, P=0.003) and without postoperative adjuvant treatment ( HR=0.145, 95% CI 0.051 to 0.414, P<0.001) were independent risk factors of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST. Ki-67 proliferation index>10% ( HR=8.381, 95% CI 1.364 to 51.487, P=0.022) was an independent risk factor of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST and without postoperative adjuvant treatment. Conclusions:The most common mutation in small intestinal primary GIST is KIT mutation, followed by wild type, no case of PDGFRA gene mutation has been found. High Ki-67 proliferation index can predict poor prognosis of patients with moderate-risk and high-risk small intestinal primary GIST. Postoperative adjuvant therapy can significantly improve the prognosis of patients with small intestinal intermediate-risk and high-risk primary GIST.

Interaction of smoking and being bullied on suicidal behaviors: a school-based cross-sectional survey in China

BACKGROUND@#Suicidal behaviors are seriously social issues among adolescents in the world. Exposed to smoking and being bullied are risk factors of suicidal behaviors. The present study was aimed to examine the interaction of smoking and being bullied on suicidal behaviors among Chinese adolescents.@*METHODS@#A total of 18,900 students were involved in the questionnaire study, in four cities of China from November 2017 to January 2018. Suicidal behaviors, smoking, and being bullied were measured by self-reported validated instruments. Chi-square tests and logistic regression were used to analyze the associations of suicidal ideation (SI)/suicidal plan (SP)/suicidal attempt (SA), smoking, and being bullied.@*RESULTS@#The prevalence of smoking, being bullied, SI/SP/SA, were 3.1%, 20.6%, 26.4%, 13.2%, and 5.2% respectively. Interaction analysis indicated that being bullied was associated with a greater increase in the likelihood of suicidal behaviors for adolescents with smoking than for those without smoking.@*CONCLUSIONS@#These finding suggest that smoking exacerbates the association between being bullied and suicidal behaviors. Future research should explore how and why smoking appears to more bully-victims than for those without smoking and how to mitigate it.

Association of status of mismatch repair protein expression and EB virus infection with clinicopathological parameters in 886 gastric adenocarcinoma patients / 中华胃肠外科杂志

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.

The clinical value of combined 68Ga-SSA/18F-FDG PET/CT imaging in neuroendocrine neoplasms / 中华核医学与分子影像杂志

Neuroendocrine neoplasms (NEN) are tumors that originate from neuroendocrine cells or peptidergic neurons. NEN can be found in a variety of organs with high heterogeneity in pathology and large difference in prognosis. Conventional imaging methods and pathological biopsy have important roles in the diagnosis of NEN, while both of them have limitations. Most NEN cells highly express several peptide receptors, especially somatostatin receptors (SSTR). Moreover, some of them have high glycolysis activity because of high proliferative activity. 68Ga-somatostatin analogs (68Ga-SSA) combined with 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging can comprehensively evaluate both the expression of SSTR and the activity of glycolysis in NEN, providing effective information for diagnosis, treatment, monitoring and prognosis. This review summarizes the current studies of combined 68Ga-SSA/18F-FDG PET/CT imaging in patients with NEN.

The clinical value of combined 68Ga-SSA/18F-FDG PET/CT imaging in neuroendocrine neoplasms / 中华核医学与分子影像杂志

Neuroendocrine neoplasms (NEN) are tumors that originate from neuroendocrine cells or peptidergic neurons.NEN can be found in a variety of organs with high heterogeneity in pathology and large difference in prognosis.Conventional imaging methods and pathological biopsy have important roles in the diagnosis of NEN,while both of them have limitations.Most NEN cells highly express several peptide receptors,especially somatostatin receptors (SSTR).Moreover,some of them have high glycolysis activity because of high proliferative activity.68Ga-somatostatin analogs (68Ga-SSA) combined with 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging can comprehensively evaluate both the expression of SSTR and the activity of glycolysis in NEN,providing effective information for diagnosis,treatment,monitoring and prognosis.This review summarizes the current studies of combined 68Ga-SSA/18F-FDG PET/CT imaging in patients with NEN.

Characteristics of amplitude of low frequency fluctuations in the frontal lobe in depression patients with different sleep quality and its relationship with memory function / 中华行为医学与脑科学杂志

Objective:To explore the association between the spontaneous neural activity and memory function in depressive patients with different sleep quality.Methods:Totally 58 patients with depressive disorder and 58 gender-, age-, education-matched healthy controls (HC) completed 3.0 T MRI Scanning and clinical assessment including Wechsler memory scale (WMS), 24 Hamilton depression scale(HAMD-24) and Pittsburgh sleep quality index (PSQI). According to the score of PSQI, patients were divided into poor sleep quality group (PS, n=38) and good sleep quality group (GS, n=20). Amplitude of low frequency fluctuations (ALFF) were calculated and compared among three groups.Correlation analyses between the brain activity and the score of WMS were conducted as well. Results:Memory quotient of WMS showed differences among three groups( F=14.163, P<0.01), and the lowest score was found in patients with low sleep quality.The brain areas showed significant differences among three groups located in the left medial superior frontal gyrus (lmSFG, MNI: x=-10, y=30, z=58; K=56), right orbital inferior frontal gyrus (roIFG, MNI: x=26, y=20, z=-26; K=24) and left middle frontal gyrus (lMFG, MNI: x=-40 y=32, z=42; K=25) (voxel size P<0.001, cluster size P<0.05, GRF corrected). Compared with GS group, the ALFF of PS group showed significantly increased in the lmSFG, which was negatively correlated with memory quotient ( r=-0.327, P=0.045) and short term memory( r=-0.388, P=0.016). Compared with HC group, the ALFF of PS group showed increased in the lmSFG and lMFG, GS group showed increased ALFF in the roIFG. Conclusion:The impairment of memory function is more serious in patients with depression of low sleep quality, and the activity of frontal lobe is abnormally increased, which is related to memory function.Their association suggests that poor sleep quality in depressive patients may impair memory function by disrupting neural plasticity and synaptic pruning in the frontal lobes.

Improved Research of Adjustable External Fixation Device for Lower Limbs Based on Semiconductor Refrigeration Sheet / 中国医疗器械杂志

A kind of adjustable external fixation device for lower extremity is designed. The circuit is mainly composed of TEC1-00703 semiconductor refrigeration chip, HZC-30A pressure sensor, STC89C52RC single chip microcomputer and other electrical components. It can realize the timing intelligent temperature control and meet the local fixed-point refrigeration. The design of adjustable structure and the application of intelligent air cushion can satisfy the full fixation of lower limbs of different individuals. Its operation does not need much medical knowledge. It can solve the problem of emergency transportation and follow-up treatment of lower limb injury in ice and snow sports. It has a good application prospect and universality.

Effect of Shugan Wendan Decoction on LXRα, NF-кB and Endothelial Function in Atherosclerosis Rabbits / 中国实验方剂学杂志

Objective:To investigate the mechanism of Shugan Wendan decoction in treating atherosclerosis based on liver X receptor α(LXRα)/nuclear factor-κB(NF-κB) signal. Method:A New Zealand rabbit model of atherosclerosis with liver-Qi stagnation was established by using calf serum albumin immune injury, high fat feeding and bondage emotional stress method. Theses rabbits are randomly divided into 6 groups, control group,model group, atorvastatin group, Shugan Wendan decoction low, medium and high dose group(2.18,6.54,19.62 g·kg-1·d-1). After successful modeling, the rabbits were treated by injecting drugs with Atorvastatin and low, middle and high dose Shugan Wendan decoction to gastric.The control group and the model group were given intragastric administration of saline in the same volume. The period of gavage is 6 weeks. The pathological changes of the rabbits were detected by hematoxylin-eosin(HE) staining.Serum levels of totalcholesterol(TC), triglyceride(TG),low density extremityprotein(LDL-C), high density extremity protein(HDL-C), nitric oxide(NO), and endothelin-1(ET-1) of the rabbits were detected by enzyme method, nitrate reductase method, and enzyme-linked immunosorbent assay(ELISA), respectively.The gene expression of CRP, IL-1β, IL-6 and MMP-9 in the aorta was detected by Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) method.The protein expression of LXRα/NF-κB signaling pathway wasdetected by Western blot. Result:Compared with normal control group, in model group, the lumen of the blood vessels was significantly narrowed, atheromatous plaques were formed, and a large number of intracellular foam-like changes were seen. In atorvastatin group and Shugan Wendan decoction group, the blood vessels in high, middle, and low concentration groups were narrowed. Atherosclerotic plaques and foam-like changes were all lower than the model group.Compared with the normal control group, the TG, TC, and LDL-C levels in the model groupincreased(PPPPβ, IL-6 and MMP-9 all increased(Pα protein in the model group was decreased(PκB was increased(PPPβ, IL-6 and MMP-9 in the atorvastatin group,the low, middle and high dose Shugan Wendan decoction groups all decreased(Pα protein in the group was increased(PκB was decreased(PConclusion:Shugan Wendan decoction can inhance the function of vascular endothelial cells and the stability of atherosclerotic plaque by regulating LXRα/NF-κB signaling pathway.

HIV-1 drug resistance and influencing factors among people living with HIV/AIDS before antiretroviral therapy in Liangshan Yi Autonomous Prefecture / 中华流行病学杂志

Objective@#To explore HIV-1 drug resistance and influencing factors among people living with HIV/AIDS before antiretroviral therapy in Liangshan Yi Autonomous Prefecture (Liangshan).@*Methods@#Between January 1 and June 30, in both 2017 and 2018, a cross-sectional survey was conducted in Liangshan HIV-1 pol sequences were gathered and analyzed according to WHO Guidelines on HIV drug resistance surveillance of 2014. Both HyPhy 2.2.4 and Cytoscape 3.6.1 software were used to analyze the drug resistant strains of HIV-1 transmission network.@*Results@#A total of 464 people living with HIV/AIDS was recruited. The proportion of HIV-1 CRF07_BC subtype was 88.6% (411/464), with HIV-1 drug resistance rate was 9.9% (46/464). The HIV-1 drug resistance rates of non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors(NRTI) and protease inhibitors (PI) were 6.7% (31/464), 1.9% (9/464) and 0.4% (2/464) respectively. New recombinant strains of HIV-1 URF_01BC subtype was independently clustered according to the drug resistant mutation sites. Results from the multivariate logistic analysis showed that injected drug users group had higher risk on HIV-1 drug resistance (aOR=3.03, 95%CI:1.40-6.54) than heterosexual group among people living with HIV/AIDS.@*Conclusions@#HIV-1 drug resistance rate had already been in a high level before antiretroviral therapy was in place. The newly identified recombinant strains of HIV-1 URF_01BC subtype were independently clustered according to the drug resistant mutation sites. It was necessary to strengthen the prevention of the HIV-1 drug resistant strains transmission.

Clinical and radiological analysis of patients with diplopia after acute lacunar infarction / 实用放射学杂志

Objective To analyze the clinical,radiological features and risk factors of diplopia in patients with acute lacunar infarction (ALI).Methods Retrospectively retrieved patients of ALI (lesion diameter was less than 1.5 cm in DWI sequence)diagnosed by MR and clinical.We further summarized 13 ALI patients with diplopia and randomly selected 13 ALI patients without diplopia as the control group. SPSS22.0 statistical software was used for statistical analysis.The general clinical data such as sex and age was compared by Ch-i square test and t-test.The risk factors were primarily analyzed by one-way ANOVA and then the risk factors with statistical significance were brought into the logistic regression model for multivariate analysis.Results The incidence of diplopia in ALI patients was about 2.7%(13/489). The infarct sites were all located in the brain stem of the oculomotor-related brain nucleus and the dorsolateral medulla oblongata.Hypertension and hematocrit were negatively correlated with diplopia after infarction (P＜0.05 ).Conclusion The incidence of diplopia is low in ALI patients.The medial longitudinal tract of the dorsolateral medulla is an important area causing diplopia.Hypertension and hematocrit are non-risk factors for diplopia after ALI.

Clinicopathological characteristics and prognostic factors of gastric neuroendocrine neoplasms: an analysis of 117 cases / 中国肿瘤临床

Objective: To explore the clinicopathological characteristics and prognostic factors of gastric neuroendocrine neoplasm (NEN). Methods: Clinicopathological parameters and follow-up data collected from 117 patients with gastric NEN at Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2017 were reviewed, classified, and graded according to World Health Or-ganization (WHO) 2010 classification. Clinicopathological characteristics of different types and grades of gastric NEN were compared and survival analysis was performed. Results: Among the 117 cases confirmed as gastric NEN, this entire cohort comprised 13 cases (11.1%) of neuroendocrine tumor (NET) G1, 6 cases (5.1%) of NET G2, 57 cases (48.7%) of neuroendocrine carcinoma (NEC), and 41 cases (35.1%) of mixed adenoneuroendocrine carcinoma (MANEC). Gastric NET G1 and G2 typically consisted of multiple small tumors with shallow invasion and infrequent lymphatic and distant metastases at early stages at the time of diagnosis. The treatment of patients with gastric NET included endoscopic submucosal dissection and radical surgical resection. Precursor neuroendocrine lesions were detected in most cases. The patients with gastric NET G1 and G2 had a good prognosis. Gastric NEC and MANEC mostly consisted of single large tumors with deep infiltration, and common lymphatic and distant metastases at advanced stages when the diagnoses were confirmed. All the patients with gastric NEC and MANEC underwent surgical resection, and most received adjuvant therapy. Histopathological changes of gastric NEC were characterized by large cells and poorly differentiated tumors, while gastric MANEC had various forms of neuroendocrine and adenocarcinoma components. The prognosis of patients with gastric NEC and MANEC was poor for both; however, the predictors of progression-free survival and overall survival were different between gastric NEC and MANEC. Conclusions: Gastric NEN are a group of heterogeneous tumors with different clinicopathological features and prognosis. More multicenter studies with large sample sizes are still needed to improve the classification of gastric NEN and explore the prognostic factors.

Study on mechanism for treating ischemic stroke of Siegesbeckiae Herba based on network pharmacology / 中国中药杂志

Xixiancao( Siegesbeckiae Herba) has the effect of treating ischemic stroke( IS),however,the mechanism has not been fully elucidated. In this study,combined with Lipinski's five principles and Veber oral bioavailability rules,68 chemical components of Xixiancao were obtained by database and literature search. Based on the reverse targeting,248 potential targets were obtained and mapped it to the ischemic stroke target set,47 potential targets for the treatment of ischemic stroke were obtained. Molecular docking technique was used to verify that the Xixiancao component has good binding activity to potential targets. GO enrichment analysis and pathway analysis were performed on potential targets using Clue GO. GO enrichment analysis showed that Xixiancao was mainly involved in life processes such as neuronal apoptosis,cholesterol storage and blood pressure regulation. Pathway analysis showed that Xixiancao may promote vascular repairing and regeneration by regulating the expression of ADAMTS1,FLT1 and KDR in VEGFA-VEGFR2 signaling pathway,activate cell survival signals and inhibit neuronal apoptosis by regulating the expression of CAMK2 AA,MDM2,MAPK1,MAPK3,CDK5 and MAPK10 in brain-derived neurotrophic factor signaling pathway and PI3 K-Akt signaling pathway. Lipid homeostasis and inflammation may also be regulated by Xixiancao through regulating the expression of ESR1,NR1 H3,PPARA,PPARG in the nuclear receptor signaling pathway. In addition,Xixiancao could also prevent platelet aggregation by regulating the expression of ITGA2 B,F2,F10,and ALB,and play an antithrombotic role. The results of this study indicate that Xixiancao plays an important role in the treatment of ischemic stroke mainly through anti-thrombosis,promoting angiogenesis,protecting neurons,anti-inflammatory and regulating blood pressure and lipids.

Anti-platelet aggregation mechanism of Xixian Tongshuan Preparation based on molecular simulation methods / 中国中药杂志

The thrombus is a deposit that is formed on the surface of the endovascular or at the site of repair,and known as the main complication of cardiovascular disease and the cause of death. At the same time,thrombus is mainly treated by the following three ways: anticoagulation,anti-platelet aggregation and thrombolysis. In this study,the chemical constituents of seven traditional Chinese medicines in the Xixian Tongshuan Preparation were collected to construct a component database. Subsequently,the pharmacophore were used to screen out the component database,and molecular docking was used to screen out the results of pharmacophore for explaining the material basis and mechanism that Xixian Tongshuan Preparation exerts anti-thrombotic activity by inhibiting platelet aggregation. First of all,P2 Y12,GPⅡb/Ⅲa and PAR1 were selected as study vectors,the optimal models of inhibitors were obtained respectively through verification and evaluation of the pharmacophore models. Afterwards,the component database was screened out by the optimal pharmacophore models of PAR1,P2 Y12 and GP Ⅱ b/Ⅲ a,and the molecular docking method was used to further refine the screening results. The screening results indicated that the anti-platelet aggregation effect of Xixian Tongshuan Preparation was correlated with the inhibition of P2 Y12,PAR1 and GPⅡb/Ⅲa expressions with saffower yellower,hirudin and candidin and notoginseng triterpenes,folinic acid,respectively. The material basis and mechanism of anti-platelet aggregation of Xixian Tongshuan Preparation provided a theoretical basis for the clinical use of the preparation and the lead compounds for the development of anti-platelet aggregation drugs.

Study on mechanism of Xixian Tongshuan Capsules based on network pharmacology / 中国中药杂志

Xixian Tongshuan Capsules with functions of promoting blood circulation and removing blood stasis,dispelling wind and resolving phlegm,relaxing muscles and activating collaterals,restoring consciousness and inducing resuscitation,has significant effects on main and concurrently symptoms of apoplexy. In this research,908 chemical compounds of Xixian Tongshuan Capsules were collected,and 337 potential targets were discovered by pharmacophore based reverse target identification. Protein interaction network( PIN)was then constructed and Identifying Protein Complex Algorithm( IPCA) was used to obtain the modules of the capsule and analyze the potential action mechanism. According to the research,Xixian Tongshuan Capsules could play a therapeutic role for hyperlipidemia and hypertension by regulating lipid metabolic process and blood pressure,the most direct risk factors of apoplexy. It could be used to treat the cerebral thrombosis and irreversible death of nerve tissue caused by insufficient supply of cerebral tissue blood and oxygen,in a way of regulating blood circulation system and nervous system. Xixian Tongshuan Capsules could also treat stroke-induced inflammation and inflammatory immune response through its regulatory effect on inflammatory immune response. Based on the network analysis,the antiinflammatory activity of Xixian Tongshuan Capsules extracts was investigated by measuring the NO release with Griess reagent method through LPS-induced in vitro inflammation model of RAW264. 7 cells. The results showed that Xixian Tongshuan Capsules extracts inhibited the secretion of NO by LPS-induced RAW264. 7 cells,indicating favorable anti-inflammatory activity. This research illuminates the mechanism of Xixian Tongshuan Capsules based on the PIN analysis at molecular network level,providing a scientific basis for its clinical application.

Clinicopathological features and prognostic factors of neuroendocrine neoplasms at different sites in the digestive system / 中国肿瘤临床

Objective:To explore the clinicopathological characteristics and prognostic factors of neuroendocrine neoplasms(NENs)at different sites in the digestive system.Methods:The clinicopathological parameters and follow-up data were collected from 284 pa-tients with NENs in the digestive system in Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2015.The incidence and clinicopathological features were compared between the cases of NENs at different sites and survival analysis was performed.Results:In this study,NENs were detected mostly frequently in the pancreas,followed by the colorectum and stom-ach.In the pancreas,neuroendocrine tumor(NET)G1(51.8%)and G2(35.8%)accounted for a large proportion of NENs.World Health Organization(WHO)grades were related to lymph node metastasis,adjacent organ invasion,and nerve invasion(P<0.05 for all)but were not associated with the overall survival time of the patients.The patients with pancreatic NENs with distant metastasis had poor overall survival(P<0.05).Regarding colorectal NENs,most patients had NET G1(82.5%),and the majority of patients were cured with endoscopic or transanal resection.Patients with NENs,lymph node metastasis,and distant metastasis had poor overall survival(P<0.05 for all).The ratio of male-to-female patients,proportion of patients aged older than 40 years,prevalence of neuroendocrine carci-nomas(NECs)and mixed adenoneuroendocrine carcinomas(MANECs),presence of lymph node and distant metastasis,and presence of advanced stage tumors were greater in patients with gastric NENs than in patients with pancreatic and colorectal NENs(P<0.05 for all).WHO grades and lymph node metastasis were associated with the overall survival time of patients with gastric NENs(P<0.05 for both).Conclusions:NENs in the digestive system are a group of heterogeneous tumors with different clinicopathological features at different sites.The distribution and clinicopathological features of Chinese patients with NENs in the digestive system are different from those of European and American patients.More multicenter studies with large sample sizes are still needed to understand the bi-ological behaviors and prognostic factors of NENs at different sites in the digestive system.

Study on cardiovascular disease risk in inpatients with schizophrenia / 中国神经精神疾病杂志

Objective To describe the cardiovascular risk profile of inpatients with schizophrenia and estimate the 10-year CVD risk in schizophrenia patients. Methods Four hundred sixty-six randomly selected cases of schizophrenia patients and 507 health controls were included in the study. Body mass index (BMI), Fasting blood glucose (FBG), triglyceride (TG),,total cholesterol (TC), smoking rate (smoking people/total people), Framing-ham Risk Score (FRS), high density lipoprotein-cholesterol (HDL-C) and age of the vessel (VA). The 10-year cardiovascular risk(FRS) and age of the vessel (VA) were assessed using the Framing-ham Risk Score. Results 10-year CVD risk was significantly higher in patients with schizophrenia than in control group [(6.71 ±6.95)％ vs. (4.76 ±3.07)％], (P<0.05). Comparing with the control group, smoking prevalence[(41％) vs. (19％)], MS[(25％) vs. (17％)], BMI[(23.67 ±3.61)kg/m2 vs. (21.73±4.11)kg/m2] and VA[(46.7±15.3) vs. (43.7±9.8)] were higher in patients group. SBP[(119.86±14.90)mmHg vs. (128.10±15.41)mmHg] and HDL-C [(1.08±0.27)mmol/L vs. (1.38±0.22)mmol/L] were lower in patients group than in the healthy controls. The FRS score of the patient group was positively correlated with BMI, FBG level and SBP, waist circumference and smoking index (P<0.05) and was negatively correlated with the levels of HDL-C. Multivariate Linear Regression analysis demonstrated that FRS was correlated with FBG (β=0.181,P<0.01)、SBP (β=0.149,P<0.01)、HDL-C (β=-0.107,P<0.01) and smoking index(β=0.554,P<0.01). Conclusion The risk of cardiovascular disease in patients with schizophrenia over the next 10 years is 6.7％, which is significantly higher compared with the control group. Fasting blood glucose, systolic blood pressure, high density lipoprotein, smoking may be associated with 10-year CVD risk of schizophrenia patients.

Clinical outcomes of cervical disc herniation treated by posterior percutaneous endoscopic cervical discectomy / 中华外科杂志

Objective@#To evaluate the clinical outcomes of posterior percutaneous endoscopic cervical discectomy (PPECD) for cervical disc herniation.@*Methods@#A total of 23 patients who underwent PPECD for cervical disc herniation at Department of Spine Surgery, Guangdong Provincial Hospital of Chinese Medicine from August 2014 to April 2016 were reviewed. The mean age of the 17 males and 6 females was 49.5 years (range from 31 to 61 years). All patients had unilateral upper limb radiating symptoms, 13 patients with right upper limb radiating pain and 10 patients with left upper limb radiation pain, 17 patients with neck pain symptoms. Responsible segment: left C4-5 1 case, right C4-5 2 cases, left C5-6 4 cases, right C5-6 8 cases, left C6-7 5 cases, right C6-7 3 example.Operating time, length of hospitalization, complications, neck and arm Visual analog scale(VAS), and Neck Disability Index(NDI) were evaluated. The excellent and good rate of surgery was evaluated by using the Odom criteria. Harrison method was used to measure cervical curvature. The Cobb angle of the surgical segment was measured on the X-ray, and the range of motion (ROM) was calculated. The changes of the cervical curvature and the surgical segment ROM were compared pre- and post-operation.@*Results@#The operation time was 94.1 min (range from 80 to 150 min). The average length of hospital stay was 4.8 days. The mean follow-up period was 23.5 months (range from 15 to 35 months). The preoperative arm VAS score was 6.95±0.88, 1-week postoperative arm VAS score was 2.09±0.67, the last follow-up arm VAS score was 1.04±0.98. The preoperative neck VAS score was 3.04±0.77, 1-week postoperative neck VAS score was 1.52±0.51 and the last follow-up neck VAS score was 0.61±0.78. The 1-week postoperative and last follow-up arm and neck VAS scores were significantly reduced compared with pre-operation (P<0.01). Compared with 1 week after surgery, the last follow-up of the arm and neck VAS score further reduced, the difference was statistically significant (P<0.01). The preoperative NDI was (58.52±4.98)%, the 1-week postoperative NDI was (33.74±4.72)%, the last follow-up NDI was (19.22±3.23)%. The 1-week postoperative and last follow-up NDI was significantly improved compared with pre-operation (P<0.01). Compared with 1 week after surgery, the last follow-up of the NDI further improved, the difference was statistically significant (P<0.01). The 1-week postoperative cervical curvature was (14.65±2.89)°, and it was improved compared with preoperative(14.23±3.06)°, the difference was statistically significant (P<0.05) . The last follow-up was cervical curvature(14.64±2.68)°, there was no significant difference compared with preoperative (P> 0.05). The preoperative surgical ROM was(5.37±1.83)°, 1-week postoperative was(5.53±1.52)°, and the last follow-up was (5.62±1.48)°, there was no significant difference pre-operative and post-operation (P> 0.05). The excellent and good rate was 91.3% (excellent in 16 cases, good in 5 cases, 2 cases). There was no nerve root injury, cerebrospinal fluid leakage, wound infection, and other complications.@*Conclusions@#PPECD is a sufficient and safe supplement for cervical disc herniation, its recent clinical efficacy was good. And it has no significant effect on cervical stability.