Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

ObjectiveTo investigate the therapeutic effect of Ganmai Dazao Tang on breast cancer-related depression and explore the mechanism of the decoction in regulating immune inflammation and neurotransmitters via the mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） pathway. MethodBALB/c mice were randomized into control， model， fluoxetine （5 mg·kg^-1·d^-1）， and low- and high-dose （crude drug 20 and 40 g·kg^-1， respectively） Ganmai Dazao Tang groups （n=10）. The mouse model of 4T1 orthotopic transplantation-induced breast cancer-related depression-like behavior was established. The depression-like behavior of mice was assessed by the tail suspension test and the forced swimming test. RT-qPCR was employed to determine the mRNA levels of interleukin （IL）-17A， forkhead box P3 （FoxP3），IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in the cerebral cortex. Flow cytometry was employed to measure the proportions of immune cell subsets in the spleen and thymus. HPLC-MS/MS was employed to measure neurotransmitter levels in the cerebral cortex. Western blotting was employed to detect the activation of the MAPK/NF-κB pathway. ResultCompared with the model group， administration of Ganmai Dazao Tang at a dose of 40 g crude drug·kg^-1 continuously for 4 weeks shortened the immobility time of modeled mice in the tail suspension and forced swimming tests （P<0.05）， down-regulated the mRNA levels of IL-1β， IL-17A， and TNF-α （P<0.05）， increased the proportions of T cells， CD4⁺ T cells， B cells， helper T 17 （Th17） cells， and regulatory T （Treg） cells， and reduced the proportion of CD8⁺ T cells （P<0.05）. Furthermore， it lowered the levels of 5-hydroxyindoleacetic acid （5-HIAA） and kynurenine （Kyn）， decreased the kynurenine/tryptophan （Kyn/Trp） ratio （P<0.05）， increased the content of 5-hydroxytryptamine （5-HT）， and down-regulated the protein levels of phosphorylated extracellular signal-regulated kinase （p-ERK）， phosphorylated p38 MAPK， and phosphorylated nuclear factor-κB p65 （P<0.05）. ConclusionGanmai Dazao Tang can down-regulate the expression of inflammatory cytokines such as IL-1β， IL-17A， and TNF-α， restore 5-HT metabolism and Kyn/Trp balance， increase the 5-HT content， and reduce the activation of p38 MAPK， ERK， and the MAPK-mediated NF-κB signaling pathway to reduce neuroinflammation in the treatment of cancer-related depression.

Objective:To evaluate the reliability and validity of the Chinese version of the Ohkuma questionnaire.Methods:The Ohkuma questionnaire was translated and revised, before it was used to investigate 70 elderly patients. Cronbach′s alpha coefficient, Cohen′s kappa coefficient and Pearson correlation were used to evaluate the scale′s internal reliability, sub-item retest reliability and total score retest reliability. KMO and Bartlett tests were used to evaluate the validity. The correlation between the Chinese version of the Ohkuma questionnaire and ratings from video fluoroscopy before and after treatment was used to evaluate the scale′s discrimination ability.Results:The Cronbach′s alpha of the Chinese version of Ohkuma questionnaire was 0.831, with 0.814 in the initial evaluation and 0.808 in a second evaluation. The Cohen′s kappas of the 15 sub-items ranged from 0.728 to 1.000. The Pearson correlation coefficient of the total score was 0.914. The scale′s KMO value was 0.701. A t-test of the Ohkuma scores before and after treatment showed a statistically significant difference.Conclusion:The revised Chinese Ohkuma questionnaire has good reliability, validity and discriminatory power. It can be used to screen for dysphagia among the elderly.

Objective:To explore the effects of health education on the knowledge and awareness of hypertension in primary and secondary school students.Methods:Twenty seven primary and secondary schools in Emin County of Xinjiang Uygur Autonomous Region were selected in 2014 as study sites; among which 24 schools were randomly assigned as the intervention group and 3 schools were assigned as control group. According to the education methods (classroom teaching, publicity manual, hypertension class reports and the combination of the three) and the frequency of education (1, 2, 3 times per semester), the intervention group were further randomly divided into 12 subgroups with 2 schools in each group. The intervention study was carried out for 3 years.Results:A total 13 402 students were involved in the study, and there were 11 333 students in the intervention group and 2 069 students in the control group. The awareness rates of hypertension concept [41.8% (4 738/11 333) vs. 24.6% (511/2 069), χ 2=154.86, P<0.01], the adverse consequences of hypertension [85.8% (9 735/11 333) vs. 75.4% (1 561/2 069),χ 2=25.80, P<0.01], the hypertension risk factors [84.3% (9 564/11 333) vs. 72.5%(1 501/2 069), χ 2=12.83, P<0.01), and the health behaviors after hypertension [84.9% (9 629/11 333) vs. 67.7%(1 402/2 069), χ 2=187.24, P<0.01] in intervention group were all significantly higher than those in control group. The stratified analysis showed that among students in elementary school, junior high school and high school, there were significant differences in the awareness rate of adverse consequences [94.4% (2 019/2 138) vs. 81.6% (3 829/4 690), 86.2% (3 887/4 505), χ 2=199.31, P<0.01], awareness rate of risk factor [86.8% (1 857/2 138) vs.86.1% (4 038/4 690), 81.4% (3 669/4 505) , χ 2=49.96, P<0.01); and awareness rate of correct behavior [89.9% (1 923/2 138) vs. 86.1% (4 037/4 690), 81.4% (3 669/4 505) χ 2=89.77, P<0.01]. Up to 95.9% (10 868/11 333) students in the intervention group liked the hypertension health education. Conclusion:Based on the school health education curriculum, the intervention measures of hypertension health education are effective, and the awareness rate of hypertension related knowledge among senior high school students is significantly improved.

Objective: To study the preventive effect of Timosaponin BⅡ (T-BⅡ) -loaded temperature/ion-sensitive nasal in situ hydrogels (ISGs) on Alzheimer's disease (AD), its preparation technology, characteristics and in vivo effects were evaluated.Methods: The morphological and rheological properties were evaluated. The preventive effects of T-BⅡ ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1 (M1) expression and pathological changes. Results: Results revealed that T-BⅡ ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1 (CA1) area. Conclusion: T-BⅡ ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine. This, thereby, lays forth a new treatment option for preventing AD.

Objective: To explore the value of videofluoroscopy in assessing the capsule swallowing ability of stroke survivors. Methods: Twenty-seven stroke survivors with functional oral intake scale ratings of 4-7 with no aspiration were selected as a patient group, while 16 healthy subjects were chosen as a control group. All swallowed capsules filled with barium sulfate with water while being monitored videofluoroscopically. The success rate of capsule swallowing was recorded along with oral transit time, stage transition time (STT), pharyngeal transition time, the upper esophageal sphincter (UES) opening time, delay time (DT), superior hyoid bone movement, anterior hyoid bone movement and UES opening diameter for each swallowing. Results: The swallowing success ratio was 78.3% in the patient group, significantly lower than in the control group. Swallowing failures manifested as hindered transport and retention of the capsule in the oral or pharyngeal cavity. Significant differences were found in STT and DT between the two groups. Conclusion Even if eating and swallowing ability recover somewhat after a stroke, survivors still have difficulty swallowing oral medication. Clinical assessment for ability to take oral medication is crucial and videofluoroscopy can be one useful tool.

Objective: To investigate the risk factors for postsurgical gastroparesis syndrome (PGS) after surgery for stomach cancer. Methods: A total of 684 patients with gastric cancer who underwent surgery for stomach cancer from Jan. 1, 2010 to Dec. 31, 2014 in Tai′an Tumor Prevention and Treatment Hospital, including 475 males and 209 females, with an average age of 59.9 years were identified and included in this study. There were 206 cases of gastric cardia and gastric fundus cancers and 478 cases of gastric antrum cancer. 206 cases underwent proximal radical subtotal gastrectomy and D2 lymph node dissection, 478 distal radical subtotal gastrectomy, 206 residual esophagogastric anastomosis, 311 Billroth-Ⅰ anastomosis, 99 Billroth-Ⅱ anastomosis, and 68 Billroth-Ⅱ plus Roux-en-y anastomosis. The incidence and risk factors of PGS were analyzed. Results: All of the 684 patients were successfully operated.Among them, 48 (7.0%)encountered PGS. The univariate analysis showed that age, smoking index, alcohol consumption index, HP infection, scores of anxiety, preoperative albumin level, preoperative pyloric obstruction, site of resection, mode of anastomosis, whether to preserve the vagus nerve trunk, perioperative blood glucose level, abdominal cavity infection, and usage of postoperative analgesia pump were related to the occurrence of PGS (P<0.05 for all), while sex, hypertension, diabetes, perioperative hemoglobin level, perioperative electrolyte imbalance, operation duration, intraoperative blood loss, size of gastric remnant and number of dissected lymph nodes were not significantly related to the occurrence of PGS(P>0.05 for all). The multivariate binary logistic regression analysis showed that age, HP infection, scores of anxiety, perioperative albumin level, preoperative pyloric obstruction, site of resection, mode of anastomosis, whether to preserve the vagus nerve trunk, perioperative blood glucose level and abdominal cavity infection were risk factors for PGS (P<0.05 for all); while the age (<67 years old), perioperative albumin level (>35 g/L) and preservation of the vagus nerve trunk were protective factors of PGS (P<0.05 for all). Conclusions The occurrence of PGS is affected by many factors. Detailed evaluation of patients′symptoms and physical signs before operation and rectifying and eliminating risk factors are important to prevent and reduce the occurrence of PGS in patients with gastric cancer.

Objective To determine the prevalence of dysphagia among elderly population and patients with stroke,head and neck cancer or neurodegenerative diseases in China.Methods Patients with stroke,head and neck cancer and neurodegenerative diseases,as well as elderly people older than 65 were selected.They were surveyed using the Sydney or Ohkuma swallowing questionnaire and evaluated using the Kubota's water swallow test and videofluoroscopic swallowing study (VFSS).The incidence of dysphagia among patients with the three diseases and elderly population was recorded,and its relationship with age,gender and economic status was also observed.Results For 7000 people surveyed,6102 met the inclusion criteria.Of all the included participants,2363 (38.7％) were identified as having swallowing abnormalities.Dysphagia was found in 46.3％ of stroke patients at the acute phase,56.9％ of stroke patients at the chronic phase,40.8％ of Alzheimer's disease patients,46.2％ of Parkinson's disease patients,12.5％ of multiple sclerosis patients,50.0％ of amyotrophic lateral sclerosis patients,36.6％ of nasopharyngeal cancer sufferers,58.4％ of laryngeal cancer sufferers.The prevalence of oropharyngeal dysphagia was 26.4％ and 13.9％ in nursing home-and community-dwelling elderly people.The average prevalence rate of deglutition disorder in the midland (55.0％) was significantly higher than the east coast (38.6％),still significantly higher than the western areas (32.5％) of China (x2=116.2,P＜0.001),representing 3 different economic development status.This study demonstrated that the prevalence of the male (40.0％) was higher than the female (36.3％).Moreover,the prevalence increased with age.Conclusion Dysphagia is of high prevalence among patients with stroke,head and neck cancers or neurodegenerative diseases,as well as the elderly in China.Its prevalence has significant correlations with age,gender and economic status.

According to the working principle of vertical ultrasonic vial washing machine, receiving respective force of small water droplets on the inside wall of vials and the minimum air velocity of blowing off water droplets can be obtained based on the analysis of water-droplet-related parameters. The inside wall model of 7 mL vial created by GAMBIT was divided into fine grids. Then the Realizable k-epsilon Two Equation Turbulence Model was adopted and the flow field of vial by FLUENT software was simulated when air was flushing inside the wall. In that case, the optimal position, inner diameter and the corresponding minimum air velocity of needle can be acquired to meet the needs of vial washing machine applied to 7 mL vial.
Equipment Design ; Models, Theoretical ; Needles ; Software

OBJECTIVETo assess the association between polymorphisms of rs3740835(C/A) and rs2604204(A/C) in KCNJ5 gene with the susceptibility to unilateral and bilateral primary aldosteronism (PA).

METHODSA total of 1043 subjects were studied, which included 83 unilateral PA patients,142 bilateral PA patients and 818 essential hypertensive(EH) patients. The polymorphism of KCNJ5 gene at rs3740835(C/A) and rs2604204(A/C) position were analyzed with a TaqMan genotyping technique.

RESULTSFrequencies of A allele and AA+AC genotype at rs3740835(C/A) in unilateral PA group were significantly higher than EH group (P < 0.05). However, the above frequencies did not show a statistical significance between bilateral PA group and EH group (P > 0.05). No statistical difference was detected in the distribution of alleles or genotypes at rs2604204 (A/C) between unilateral PA and EH group or between bilateral PA and EH group. Haplotypic frequencies of C-A and A-A in unilateral PA group were significantly higher and lower than EH group, respectively. However, there was no statistical difference in the haplotype distribution between bilateral PA and EH groups.

CONCLUSIONRs3740835(C/A) polymorphism may be associated with unilateral PA but not with bilateral PA. rs2604204(A/C) polymorphism is not associated with either unilateral or bilateral PA. Haplotype C-A and A-A may respectively be susceptibility factor and protective factor for unilateral PA. No haplotype has been found to associate with bilateral PA.

Adult ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; genetics ; Haplotypes ; Humans ; Hyperaldosteronism ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic