Objective To summarize the progress on the injury mechanism of vascular endothelial cells in atherosclerosis.Methods The latest progress was reviewed in recent literatures.Results All kinds of etiological factors have activated NF kappa B and cytokines in the development of atherosclerosis, which lead to expression of cell adhesive molecules and adhesion of monocytes to vascular endothelial cells.A variety of inflammatory mediums are released, which can directly damage endothelial cells.Besides, the inflammatory mediums make monocytes and neutrophils attach to endothelial cells by immune mechanisms, which injure the endothelial cells more severely. Meanwhile the damaged membrance structure leads to the production of AECA which activates the complementary system. Then the vascular endothelial cell injury is aggravated and the development of atherosclerosis accelerated. Conclusion It is very important to recognize the injury mechanism of vascular endothelial cells in the development of atherosclerosis for prevention and treatment of atherosclerosis.

ObjectiveTo investigate the treatment effects of comprehensive nursing intervention on patients with chronic obstructive pulmonary disease(COPD) treated by non-invasive mechanical ventilation with BiPAP mode.Methods96 patients with diagnosed COPD and using non-invasive mechanical ven- tilation with BiPAP mode were randomly divided into the control group(46 cases) which was treated with routine measures and the comprehensive nursing intervention group (50 cases) which adopted comprehen- sive nursing intervention according to experimental design. The frightening degree, incidence rate of com- plications and clinical treatment effect by ventilator were compared between the two groups.ResultsPa- tients compliance with treatment and clinical treatment effect by ventilator in the comprehensive nursing in- tervention group was better than that of the control group. The frightening degree and incidence rate ofcomplications were lower than those of the control group (P < 0.01 ).ConclusionsComprehensive nurs-ing intervention with non-invasive mechanical ventilation with BiPAP mode can improve the treatmentcompliance of COPD patients,reduce complications followed by non-invasive mechanical ventilation andreach the prospective treatment effect.

Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.

Exosome, a membranous vesicle with biological activity, not only transmits active substances between cells but also transfers information between cells to participate in cell communication. Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells acquire migratory and invasive properties to become mesenchymal stem cells. EMT is essential for the development of a spectrum of diseases. Studies have shown that exosomes have dual effects on EMT to, on the one hand, promote EMT and tumor cell invasion and metastasis and accelerate angiogenesis and tumor growth; on the other hand, exosomes can suppress tumor cell invasion, inhibit fibrosis of the heart, liver and kidney, and improve myocardial infarction by inhibiting EMT. Exosomes modulate EMT-related signaling pathways by carrying EMT-related proteins or miRNA to exert their bi-directional regulatory effects.
Epithelial-Mesenchymal Transition ; Exosomes ; Humans ; MicroRNAs ; Neoplasms ; Signal Transduction

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

ObjectiveLipopolysaccharide （LPS）-induced zebrafish inflammation model was used to evaluate the anti-inflammatory activity of different extracts from Lianggesan （LGS） and its component Glycyrrhiza Radix et Rhizoma. MethodDifferent polar fractions of LGS and Glycyrrhiza Radix et Rhizoma were obtained by the principle of similar miscibility. For toxicity observation， the zebrafish （3 day-post-fertilization） was exposed to different concentrations of extracts for 24， 48 and 72 h. The yolk sac of the zebrafish was microinjected with 0.5 g·L^-1 LPS to establish the inflammation model， and then the embryos were soaked with different concentrations of extracts to observe their survival status at 72 h and the aggregation of neutrophils in yolk sac at 12 h after treatment. Hematoxylin-eosin staining was used to analyze the yolk sac of the zebrafish microinjected with LPS. Quantitative Real-time polymerase chain reaction （Real-time PCR） was performed to further investigate the anti-inflammatory effects and mechanisms of LGS and Glycyrrhiza Radix et Rhizoma. ResultThe toxicity of LGS and Glycyrrhiza Radix et Rhizoma was decreased with the increase of polarity， and the descending order was petroleum ether>ethyl acetate>n-butanol>water. Compared with model group， the extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma prolonged the survival time of the zebrafish， and inhibited the recruitment and aggregation of neutrophils and decreased the infiltration of inflammatory cells in the yolk sac， among which the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma had the most significant effect （P<0.01）. In addition， compared with model group， the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma down-regulated the mRNA expression of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， and suppressed the expression of toll like receptor 4 （TLR4） and nuclear factor kappa-B （NF-κB） in LPS-stimulated zebrafish （P<0.01）. ConclusionThe extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma exerted protective effects in LPS-induced zebrafish by inhibiting the TLR4 and NF-κB signaling pathways. Moreover， in zebrafish model， the method of administration by soaking was applicable to the high-throughput screening of anti-inflammatory Chinese medicine， which was suitable for the evaluation of anti-LPS activity of Chinese medicine and the different extracts.