Objective The mechanical model of nonlinear blood flow in large blood vessels is developed and the propagation of nonlinear pressure wave is studied.Methods Taking the effect of large deformation,nonlinear equation of motion was established in the current configuration in terms of the constitutive equations proposed by Demiray for soft biological tissues.Resuit Employing the reductive perturbation method the KdV equation is derived from the nonlinear partial equations governing the motion of coupled system.Conclusions It is shown from this study that the system may have an accurate periodic wave solution or solitary wave solution under certain conditions.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Objective To investigate the expression of maternal embryonic leucine zipper kinase (MELK) in esophageal squamous cell carcinoma and its significance. Methods The surgical resection specimens of 139 patients with esophageal squamous cell carcinoma who were admitted to Peking University Cancer Hospital from August 2009 to July 2013 were selected. MELK expression in esophageal squamous cell cancer tissues was detected by immunohistochemistry. The relationship between MELK expression and clinicopathological characteristics of patients was analyzed. MELK expression in 6 esophageal squamous cell carcinoma cell lines (ECA109, KYSE150, KYSE30, KYSE70, KYSE180 and KYSE510) was tested by Western blot, and the cell line with high MELK expression was selected, and the expression of MELK was knocked down by lentiviral infection. The effect of MELK on tumor cell migration and invasion was examined by Transwell method, and the effect of MELK on cell proliferation was verified by CCK-8 method. Results MELK is highly expressed in 100 cases (71.9％) of esophageal squamous cell carcinoma, and the positive expression rate of MELK in patients with stage T3-T4 was higher than that in patients with stage T1-T2 (χ2=4.702, P= 0.030). The poor differentiation and lymph node metastasis inclined to higher MELK positive expression rate, but the difference was not statistically significant (χ2 = 2.761, P= 0.097; χ2= 0.994, P=0.319). MELK was highly expressed in ECA109 and KYSE150 cells. The Transwell test results showed that the number of migrating cells of EEL109 and KYSE150 cells in the MELK knockdown group was decreased when compared with the negative control group [(77±10) cells vs. (126±8) cells, t=6.56, P<0.05;(37±4) cells vs. (105 ±3) cells, t= 24.27, P< 0.05], and the number of invading cells was decreased [(47 ±7) cells vs. (154±9) cells, t= 17.08, P< 0.05; (37±2) cells vs. (184±4) cells, t= 54.09, P< 0.05]. CCK-8 proliferation studies showed that the proliferation of ECA109 and KYSE150 cells in the MELK knockdown group was inhibited (both P< 0.05). Conclusions The high MELK expression in patients with esophageal squamous cell carcinoma is associated with T stage. High expression of MELK can promote the proliferation and invasion of tumor cells in esophageal squamous cell carcinoma.

[Objective]To investigate the effects of Kuanxiong aerosol(KXA)on pyroptosis and inflammatory response in isoproterenol(ISO)-induced myocardial infarction(MI)rats,and its effect on the key pathway of pyroptosis Toll-like receptor 4(TLR4)/myeloid differentiation primary response gene 88(MyD88)/NOD-like receptor pyrin domain containing 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1).[Methods]Thirty male Wistar rats were randomly divided into five groups,6 rats in each group,as control group(0.9％sodium chloride solution),model group(ISO 120 mg·kg-1),isosorbide mononitrate(IMSN)group(ISO 120 mg·kg-1+IMSN 5 mg/kg·d),KXA low dose group(ISO 120 mg·kg-1+KXA 0.1 mL/kg·d),and KXA high dose group(ISO 120 mg·kg-1+KXA 0.3 mL/kg·d),gave continuous intragastric administration for 14 days,and intraperitoneal injection of ISO on the 13th and 14th day.After the last intervention,collected heart tissues and blood under anesthesia.Enzyme-linked immunosorbent assay(ELISA)was performed to investigate the expression of creatine kinase-MB(CK-MB)and cardiac troponin T(cTnT),as well as serum inflammatory indicators such as interleukin-1β(IL-1β),interleukin-18(IL-18),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).The histopathological changes in heart tissue were evaluated using hematoxylin-eosin(HE)staining,and RNA-sequencing was used to detect the differential expression genes among groups.And the expression of the pyroptosis relevant protein was detected by Western blot.[Results]The results of the ELISA showed that CK-MB and cTnT expression in model group were significantly higher than those in control group(P＜0.01),which meant successful model construction.Pathological staining results showed disordered and fractured muscle fibers were significantly improved after KXA and IMSN intervention.RNA-seq results showed there were 2 646 different genes between model group and control group,while 714 other genes were in KXA and model group.After analyzing these two compared groups,it found that there were 130 up-regulated genes and 7 down-regulated genes;among them,inflammation related TLR4 pathway was significantly enriched.Furthermore,compared with model group,the expression of inflammatory factors IL-1β,IL-18,IL-6 and TNF-α decreased significantly in KXA groups and IMSN group(P＜0.01,P＜0.05),and Western blot showed that the protein expression of TLR4,MyD88,phospho-nuclear factor-KB(p-NF-KB)p65,NLRP3,cleaved cysteinyl aspartate specific proteinase-1(cleaved caspase-1)and Gasdermin D-N(GSDMD-N)increased significantly in model group while significantly down-regulated in KXA groups and IMSN group(P＜0.05,P＜0.01).[Conclusion]KXA can improve myocardial ischemia,reduce cardiac damage,and inhibit cardiomyocyte pyroptosis and inflammatory response,the mechanism may be related to regulating the TLR4/MyD88/NLRP3/caspase-1 signaling pathway.

BACKGROUND: IIIa-N2 non-small cell lung cancer was significant different in survival, although N stage of lung cancer based on anatomic location of metastasis lymph node. Lymph node ratio considered of prognostic factor might be the evaluation index for IIIa-N2 non-small cell lung cancer prognosis. Therefore, the aim of the study was to evaluate the correlation between lymph node ratio and clinicopathological features and prognosis of IIIa-N2 non-small cell lung cancer prognosis. METHODS: A total of 288 cases of pathological IIIa-N2 non-small cell lung cancer were enrolled who received radical resection at the Department of Thoracic Surgery II, Peking University Cancer Hospital from January 2006 to December 2016. The univariate analysis between clinicopathological variables and lymph node ratio used Pearson's chi-squared test. Cox regression was conducted to identify the independent prognosis factors for IIIa-N2 non-small cell lung cancer. RESULTS: There were 139 cases in the lower lymph node ratio group, another 149 cases in the higher lymph node ratio group. Adenocarcinoma (χ²=5.924, P=0.015), highest mediastinal lymph node metastasis (χ²=46.136, P<0.001), multiple-number N2 metastasis (χ²=59.347, P<0.001), multiple-station N2 metastasis (χ²=77.387, P<0.001) and skip N2 lymph node metastasis (χ²=61.524, P<0.001) significantly impacted lymph node ratio. The total number of lymph node dissection was not correlated with the lymph node ratio (χ²=0.537, P=0.464). Cox regression analysis confirmed that adenocarcinoma (P=0.008), multiple-number N2 metastasis (P=0.025) and lymph node ratio (P=0.001) were the independent prognosis factors of disease free survival. The 5-year disease free survival was 18.1% in the higher lymph node ratio group, and 44.1% in the lower. Lymph node ratio was the independent prognosis factor of overall survival (P<0.001). The 5-year overall survival was 36.7% in the higher lymph node ratio group, and 64.1% in the lower. CONCLUSIONS Lymph node ratio was correlative with the pathology, highest mediastinal lymph node metastasis, multiple-number N2 metastasis, multiple-station N2 metastasis and skip N2 lymph node metastasis. Lymph node ratio was the independent prognosis factor for IIIa-N2 non-small cell lung cancer.

Objective    To evaluate the prognosis of different node status on the basis of the eighth TNM classification for lung cancer. Methods    We retrospectively reviewed the clinical data of 1 851 non-small cell lung cancer (NSCLC) patients who underwent radical resection between January 2005 and December 2014. There were 1 078 males and 773 females at age of 16–86 (59.7±9.7) years. Survival probability was estimated by the Kaplan-Meier method and significance was assessed by the log-rank test. Results    This cohort study was consisted of 1 209 patients with N0, 305 with N1 and 337 with N2. N0 patients were divided into a N0a group and a N0b group according to whether the 13 and 14 level of lymph nodes were examined. The survival rate of the N0a group was significantly higher than that of the N0b group, and the 5-year survival rate was 88.9% and 81.3% (P<0.001), respectively. According to the number of lymph node metastasis stations, N1 was divided into a N1a (single) group and a N1b (multiple) group. And no significant difference was observed between the two groups in survival rate (P=0.562). Based on the presence of lymph nodes of 10–12 level, N1 was divided into a negative group and a positive group. And the negative group was found with significantly higher survival rate than the positive group (5-year survival rate of 78.4% vs. 64.3%, P=0.007). The N2 patients were divided into a single station metastasis group (a N2a1 group), a single station with N1 positive group (a N2a2 group) and a multiple station group (a N2b group), and the percentage was accounted for 22.0% (74/337), 37.7% (127/337) and 40.3% (136/337), respectively. There was a statistical difference in 5-year survival rate (62.2% vs. 56.5% vs. 37.3%) among the three groups (P=0.001). Conclusion    Subgroup analysis of N staging in NSCLC patients shows significant survival differences which may be more consistent with multidisciplinary therapy under precise staging patterns.