Objective: Invasion and metastasis are the main causes of carcinoma mortality; hence, the timely blocking of the invasion and metastasis of carcinoma has become a research hotspot. The present study aims to investigate the expression levels of Tiam-1 mRNA and HPA-1 mRNA and their correlation with the invasion and metastasis of hepatocellular carcinoma. Methods: From May 2009 to Jan 2012, 65 hepatocellular carcinoma patients admitted consecutively in our hospital for surgical treatment were included in this study. Real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to investigate the expression levels of Tiam-1 mRNA and HPA-1 mRNA in hepatocellular carcinoma, paired adjacent hepatocellular carcinoma (2 cm from the carcinoma), and surgical marginal normal hepato mucosa tissues (5 cm from the carcinoma). RT-PCR was also used to analyze their correlation with the clinicopathological characteristics of hepatocellular carcinoma. Results: The expression level of HPA-1 mRNA was significantly higher in hepatocellular carcinoma (43.83±11.62) than in paired adjacent hepatocellular carcinoma (14.82±8.16) and normal hepato mucosa tissues (6.02±5.36) (P<0.001). The expression level of HPA-1 mRNA was higher in paired adjacent hepatocellular carcinoma than in normal hepato mucosa tissues (P<0.05). The expression of Tiam-1 mRNA was higher in hepatocellular carcinoma (35.28±11.81) than in paired adjacent hepatocellular carcinoma (12.94±6.25) and normal hepato mucosa tissues (4.17±3.49) (P<0.05). The expression level of Tiam-1 mRNA was higher in paired adjacent hepatocellular carcinoma than in normal hepato mucosa tissues (P<0.05). The expression levels of Tiam-1 mRNA and HPA-1 mRNA were closely associated with the degree of differentiation, depth of infiltration, lymph node metastasis, vessel metastasis, and TNM (Tumor, Node, Metastasis)staging of gastric carcinoma (P<0.05). Spearman rank correlation analysis demonstrated a significant correlation between Tiam-1 and HPA-1 (OR=0.523, P<0.05). Conclusion: The expression levels of Tiam-1 mRNA and HPA-1 mRNA were high in hepatocellular carcinoma. Meanwhile, the increased ex-pression levels of Tiam-1 and HPA-1 can promote the invasion and metastasis of hepatocellular carcinoma. Moreover, the determination of Tiam-1 and HPA-1 may be valuable for the treatment and prognosis of hepatocellular carcinoma.

Objective: To explore the association of the serum levels of cytokine IL-10 with the occurrence of cachexia from patients with low-third gastric cancer. Methods: Radioimmunoassay was used to examine the serum levels of IL-10 in 150 patients with low-third gastric cancer and 135 healthy controls. Results: The serum levels of IL-10 were significantly higher in patients with low-third gastric cancer than controls(Z=-11.862, P<0.01). The serum levels of IL-10 were significantly higher in patients with low-third gastric cancer of clinical stageⅢ/Ⅳ than those with clinical stageⅠ/Ⅱ(Z=-10.028, P<0.01). The serum levels of IL-10 were significantly higher in patients with cachexia than those without(Z=-10.369, P<0.01). Logistic regression analysis showed that IL-10 was associated with odds ratios of 1.599 (95%CI:1.299-1.870, P<0.01) for cachexia. Conclusion: The serum levels of IL-10 are possibly associated with the occurrence of cachexia from patients with low-third gastric cancer.

Objective To explore the angiogenesis&neovascularization effects of naringin treatment in ovariectomized rats’fracture healing. Methods Upper 1/3 transverse tibial fracture model 4 weeks later after ovariectomized were estimated and randomly divided into the naringin group and control group. Microfil perfusion technique was used to analysis the angiogene?sis situation at two weeks after bone fracture. HE staining was used to evaluate the level of angiogenesis&neovascularization of tis?sue from histological point of view. The relative expression of VEGF in the callus was identified by real?time polymerase chain re?action. Immunohistochemical technique was used to observe the vessel endothelial growth factor?2 in the callus of the two groups. Maximum fracture load was tested by three?point bend test. Results The vascular volume and vascular density were more in nar?ingin group than control group. The HE staining of the 2 week group slices shows that the VA, VN2 of the unit of high magnifica?tion vision of the naringin group was significantly larger compared to the control group. Real?time PCR revealed that the compara?tive expression of VEGF is more in naringin group than in control group; the positive number of VEGFR?2 is more in naringin group than in control group. Naringin can promote the maximum load of the callus. Conclusion Naringin can promote ovariecto?mized rats’angiogenesis&neovascularization in the early process of fracture healing. It may be act on the signaling pathway of VEGF/VEGFR?2.

ObjectiveTo investigate the clinical effect of entecavir (ETV) combined with Fuzheng Huayu capsules in the treatment of patients with compensated chronic hepatitis B-related cirrhosis. MethodsA total of 142 patients with compensated chronic hepatitis B-related cirrhosis who visited the Sixth People′s Hospital Qingdao from January 2013 to December 2015 were randomly divided into treatment group and control group, with 71 patients in each group. Both groups were given conventional treatment such as liver-protecting and symptomatic treatment. The patients in the control group were given ETV 0.5 mg/day, while those in the treatment group received oral administration of Fuzheng Huayu capsules 1.5 g twice a day in addition to the treatment in the control group. Both groups were treated for 12 months. The changes in inflammatory factors and fibrosis markers were observed. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsAfter the 12-month treatment, the treatment group and the control group showed no significant difference in the serum HBV DNA clearance rate ［91.5% (65/71) vs 90.1% (64/71), P=0.771］. Compared with the control group, the treatment group showed significant reductions in serum hyaluronic acid, laminin, procollagen type III, collagen type IV, alanine aminotransferase, aspartate aminotransferase, liver stiffness measurement, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and hypersensitive C-reactive protein (hs-CRP) (t=16187，5343，13697，17121，7409，27371，7973，5471，7885，9057，8171，all P＜0.001). ConclusionCompared with ETV alone, ETV combined with Fuzheng Huayu capsules exerts a better anti-fibrotic effect and can inhibit the release of TNF-α, IL-6, IL-8 and hs-CRP in patients with compensated chronic hepatitis B-related cirrhosis.

Objective: To evaluate the diagnostic value of BRAF V600E mutation combined with shear wave elastography(SWE) for thyroid nodules of Bethesda Ⅲ diagnosed by fine-neddle aspiration(FNAC). Methods: One hundred and seventeen thyroid nodules diagnosed as Bethesda Ⅲ in the department of ultrasound and confirmed by BRAF V600E gene detection, SWE examination and surgery were collected. BRAF V600E detection, SWE examination and both combined with pathological results were using to retrospective analysis. Results: There were 75 benign nodules and 42 malignant nodules according to pathology. Sensitivity and negative predictive value of BRAF V600E combined with SWE were higher than single BRAF V600E mutation detection and SWE with statistically significant(P=0.01, 0.001; P=0.029, 0.01, respectively). There were no statistically differences between single BRAF V600E mutation detection and SWE for Bethesda Ⅲ nodules(P=0.483, 0.645). Conclusions BRAF V600E mutation detection combined with SWE can improve the sensitivity and negative predictive value in the diagnosis of Bethesda Ⅲ thyroid nodules.

Objective To explore the status quo of job stress and happiness in nurses of three grade A hospitals and mediation effects of hope between above two elements. Methods A cross-sectional survey was conducted. The Hope Status Scale, The Nurse's Job Stressor Scale, General Well-Being Schedule and self-designed demographic questionnaire were delivered to 1200 nurses from nine hospitals. Results The path analysis results showed that the direct effect of job stress on the subjective well-being was-0.193, the indirect effect was (-0.486) × 0.456=-0.222, the total effect of working pressure on the subjective well-being was-0.415, the indirect effect of total effect was 53.49％. want direct effect on subjective well-being of 0.456, job stress on the direct effect of hope for-0.486. Conclusion Hope to play an intermediary role between nurses' job stress and subjective happiness. In the process of trying to reduce nurses' job stress, we should make full use of the intermediary significance of hope to help nurses with low level of hope to build hope and improve their happiness level.

Objective To explore the safety and clinical value of percutaneous ultrasound‐guided core needle biopsy( PUS‐CNB) and endoscopic ultrasound‐guided fine needle aspiration( EUS‐FNA ) in pancreas mass . Methods Ultrasound‐guided biopsy were performed in 109 cases who were difficult to diagnose to get specimens from the highly suspicious parts of the lesions by avoiding vessels . PUS‐CNB were performed in 82 cases , EUS‐FNA in 19 cases and both in 8 cases . T he site and size of lesions were recorded preopeartion . Specimens with clear pathological diagnosis were considered as satisfactory materials . Specimens that were impossible to puncture due to the existence of high risk factors in the process of puncture were considered as unsuccessful biopsy . All patients were followed up after biopsy and complications were recorded . Results The satisfaction rate and success rate of PUS‐CNB were 98 .89% and 100% ,the diagnostic accuracy and false negative rate were 97 .78% and 2 .22% . T he satisfaction rate and success rate of EUS‐FNA were 96 .15% and 96 .30% ,the diagnostic accuracy and false negative rate were 80 .77% and 23 .81% . T here were no serious complications such as pancreatic fistula ,hemorrhage and needle transfer at the needle site after puncture . Conclusions Both PUS‐CNB and EUS‐FNA are safe and effective methods for the diagnosis of benign and malignant pancreatic lesions and have high clinical values . Reasonable selection of EUS‐FNA and PUS‐CNB can safely and reliably identify and diffentiate the benign and malignant pancreatic lesions .

OBJECTIVE： To collect and summarize the pharmacoeconomic studies of adalimumab in the treatment of ankylosing spondylitis， and to explore the economics of adamumab in the treatment of ankylosing spondylitis. METHODS：Retrieved from Medline， Embase， Web of Science， VIP， CJFD and Wanfang databases， Chinese search terms included “adalimumab” “humira” “ankylosing spondylitis” “cost effectiveness” “pharmacoeconomic evaluation” “cost utility” “cost efficacy” etc. English search terms included “Adalimumab” “Humira” “Ankylosing spondylitis” “AS” “Cost effectiveness” “Pharmaceutical economic evaluation” “Pharmacoeconomics” “Cost utility” “Cost efficacy”， etc. The language is Chinese or English.The retrieval time was from January 2002 to May 2019. The pharmacoeconomic studies of adalimumab vs. traditional treatment，adalimumab vs. other biological agents in the treatment of ankylosing spondylitis were collected， including cost analysis， cost-effectiveness analysis， cost-effectiveness analysis and cost-benefit analysis.The included studies were summarized in terms of countires， research method and economic evluation results. RESULTS：Six papers were included， involving six studies. The literature was mainly distributed in the UK， Canada and the Netherlands. The Markov model was most commonly used.The incremental cost-effectiveness ratio of adalimumab in the treatment of ankylosing spondylitis was￡19 275-26 556 in UK， and adalimumab had cost-effectiveness advantage. The cost-effectiveness advantage between adalimumab and other biological agents was varied in different studies. CONCLUSIONS： Compared with conventional therapy， adalimumabhas economic advantages in the treatment of ankylosing spondylitis in UK. But there was lack of relevant research in China， which needs to be carried out urgently.

Augmented renal clearance （ARC）refers to the significant enhancement of patients ’renal function ，which is manifested by the significant increase of glomerular filtration rate ，which increases the clearance of drugs ，and the effective blood drug concentration cannot be achieved under the conventional dose. The efficacy of antibiotics is closely related to the concentration. The influence of renal dysfunction on drug metabolism is an important factor that clinicians should consider when determining the dosage. This article reviews the definition ，risk factors ，occurrence mechanism ，evaluation methods of ARC ，as well as its impact on the pharmacokinetics/pharmacodynamics of antibiotics and administration methods. It is found that ARC widely exists in critically ill patients ，and the risk factors include age （≤50 years old ），brain trauma ，sepsis，multiple trauma ， etc. When using antibiotics in ARC patients ，the therapeutic effect of drugs can be improved by increasing the dosage ，prolonging the duration of administration and increasing the frequency of administration. However ，in order to prevent adverse reactions caused by high concentration accumulation of drugs ，it is recommended to try to combine treatment drug monitoring.

Objective: To explore the safety and clinical value of percutaneous ultrasound-guided core needle biopsy(PUS-CNB) and endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) in pancreas mass. Methods: Ultrasound-guided biopsy were performed in 109 cases who were difficult to diagnose to get specimens from the highly suspicious parts of the lesions by avoiding vessels. PUS-CNB were performed in 82 cases, EUS-FNA in 19 cases and both in 8 cases. The site and size of lesions were recorded preopeartion. Specimens with clear pathological diagnosis were considered as satisfactory materials. Specimens that were impossible to puncture due to the existence of high risk factors in the process of puncture were considered as unsuccessful biopsy. All patients were followed up after biopsy and complications were recorded. Results: The satisfaction rate and success rate of PUS-CNB were 98.89% and 100%, the diagnostic accuracy and false negative rate were 97.78% and 2.22%. The satisfaction rate and success rate of EUS-FNA were 96.15% and 96.30%, the diagnostic accuracy and false negative rate were 80.77% and 23.81%. There were no serious complications such as pancreatic fistula, hemorrhage and needle transfer at the needle site after puncture. Conclusions Both PUS-CNB and EUS-FNA are safe and effective methods for the diagnosis of benign and malignant pancreatic lesions and have high clinical values. Reasonable selection of EUS-FNA and PUS-CNB can safely and reliably identify and diffentiate the benign and malignant pancreatic lesions.