Objective　To investigate the relationship between the tumor angiogenesis and the clinicopathological variables of hepatocellular carcinoma (HCC) and determine whether tumor angiogenesis can be used as an indicator for predicting invasion, metastasis and prognosis of HCC. Methods　Using the immunohistochemical S-P method, CD34 expression was detected in liver tissue from 20 normal individuals, 20 patients with liver cirrhosis and 85 patients with HCC and juxtacancerous tissues and the microvascular density (MVD) determined in those from 85 patients with HCC. Results　CD34 was mainly located in the cell cytoplasm of endothelial cells. The CD34 staining was confined to vessels in the portal triad in the above-mentioned various tissues. In HCC tissues, however, sinusoid-like vessels reacted intensively with anti-CD34 and the MVD was 156.5±62.4 (per 0.74 mm2). MVD was correlated to tumor size, number, differentiation, emboli in the portal vein and capsule (P<0.05 or 0.01) but not to HBsAg and AFP (P>0.05). It was also correlated with prognosis of HCC. The mean tumor-free survival of MVD ≥156 was 14 months while that of MVD <156 was 53 months (P<0.01). Conclusion　The expression of CD34 in sinusoid-like vessels in HCC tissues represents the neovascularization. Angiogenesis in HCC is associated with the progression of HCC. MVD can be used as an indicator to judge the invasion, metastasis and prognosis of HCC.

OBJECTIVETo analyze the risk factors of liver metastasis in patients after radical resection of pancreatic cancer.

METHODSOne hundred and twenty-four patients with non-metastatic, resectable pancreatic cancer treated in our department between 2006 and 2012 were included in this study. All of these patients underwent resection of the primary tumor combined with extensive lymph node dissection. The development of postoperative liver metastases was carefully followed up, and the clinicopathological factors and molecular characteristics were evaluated by univariate analysis and multivariate logistic regression using SPSS 16.0 software.

RESULTSForty-eight cases of liver metastases were found among the 124 cases of pancreatic cancer after radical surgery (38.7%). The rate of liver metastasis of pancreatic cancer after radical surgery in the age groups < 40, 40-60, and > 60 were 68.8%, 33.3% and 35.1%, respectively. The rate of liver metastasis in the body mass index (BMI) group < 20 kg/m2, 20-25 kg/m2, and > 25 kg/m2 were 21.6%, 44.1% and 52.6%, and the rate of liver metastasis in the time between the onset and diagnosis groups ≥ 3 months and < 3 months were 59.4% and 31.5%, respectively. The rate of liver metastasis in patients with preoperative fatty liver was 14.3% and it was 43.7% in patients without preoperative fatty liver. The rate of liver metastasis in patients of histological high, medium and low grade was 10.0%, 35.4% and 49.0%, respectively. The rate of liver metastasis in patients with venous tumor thrombus was 68.8% and it was 34.3% in patients without venous tumor embolus. The rate of liver metastasis in patients with postoperative chemotherapy was 31.2% and it was 51.1% in patients without postoperative chemotherapy. All those differences had statistical significance (P < 0.05). Univariate analysis revealed that age, body mass index (BMI), time between the onset and diagnosis, preoperative fatty liver, histological grading, tumor invasion depth, venous tumor embolus, and postoperative chemotherapy were significantly related to postoperative liver metastasis. Multivariate analysis revealed five statistically independent risk factors for postoperative liver metastasis: BMI, time between onset and diagnosis, preoperative fatty liver, histological grading, and venous tumor embolus.

CONCLUSIONSOur data suggest that patient's BMI, time between onset and diagnosis, histological grade, and venous tumor embolus are significantly correlated with postoperative liver metastases in patients with pancreatic cancer. Pancreatic cancer patients with preoperative fatty liver have less postoperative liver metastasis.

Adult ; Aged ; Body Mass Index ; Humans ; Liver Neoplasms ; secondary ; Lymph Node Excision ; Middle Aged ; Pancreatic Neoplasms ; pathology ; surgery ; Regression Analysis ; Risk Factors

Objective To analyse tratment strategies and to evaluate the relation between different therapies and survival rate of patients of with asynchronous liver metastases after pancreatic cancer surgery (PCLM).Methods From January 2006 to January 2012,48 patients with PCLM were included in this study,and their medical records were retrospectively analyzed.Results Among the 48 patients,27 cases of liver metastases were found within six months after surgery,and the survival rate for 1,3 and 5 years was 22.2％,3.7％ and 0％,respectively,with the median survival of 6 months,and 21 cases of liver metastases were found after six months,and the survival rate for 1,3 and 5 years was 85.7％,30.6％ and 9.2％,with the median survival of 15 months,and the difference between the two groups was statistically significant (P ＜ 0.01).After pancreatic cancer surgery and adjuvant gemcitabine chemotherapy,the probability of liver metastases was 33.3％ (8/24) within six months,the median disease-free survival time was 8 months and the disease-free survival rate for 1,3 and 5 years was 20.8％,4.3％ and 0％.For patients without adjuvant gemcitabine chemotherapy,the probability of liver metastases was 79.2％ (19/24),the median disease-free survival time was 3 months and the disease-free survival rate for 1,3 and 5 years was 4.2％,0％ and 0％,and the difference between the two groups was statistically significant (P ＜ 0.01).The overall survival for patients undergoing resection of liver metastases combined with gemcitabine treatment was better than the other groups (P ＜ 0.01).And the overall survival for patients undergoing transhepatic arterial embolization (TACE) combined with gemcitabine treatment was better than TACE group,gemcitabine group or the observation group (P ＜0.05).There were no difference in overall survival between TACE group,gemcitabine group and observation group.Conclusions Pancreatic cancer patients who develop liver metastasis within six months after surgery have poor prognosis,but postoperative chemotherapy can delay the development of liver metastasis.For patients with resectable lesion,resection of asynchronous liver metastasis is the treatment of choice,and TACE combined with gemcitabine has better efficacy than that of single treatment.

Objective To synthesis,nine N-[3-(2-furanyl)-acryloyl]-N'-substituted benzyl piperazine derivatives were synthesized and evaluated for their primary biological activities.Methods First, the furylacrylic acid was synthesized, Then the target compounds could be obtained by direct furylacrylic acid with the different substituted benzyl piperazine derivatives.In the biological active experiments, taking the different concentrations, comparing with the blank test, the inhibitory effect of the target compounds on VSMC proliferation was investigated by MTT.Results The successful synthesis of nine new compounds.The method was mild and get high yields.The structures of these compounds were confirmed by IR 1 H-NMR, MS, and elemental analysis.The results of preliminary activity test showed that the synthesized products exhibited inhibitory activity at different concentrations , and the highest inhibitory rate was 15μg/mL.Pharmacological results showed that the compounds 3e, 3f and 3 g showed the moderate inhibitory activities against vascular smooth muscle cells proliferation were higher than other compounds , and were worth further studying.Conclusion The synthesized compounds have inhibitory activities and could very well lead to the development of novel types of treat atherosclerosis drug .

Objective To investigate rite effects of loag-term exposure to low-level sevoflurane on reproductive function in mice.Method F0ny male ICR mice,aged 60 d,weighlag 20-25 g,were randomly divided into 4 groups(n=10 each):control group received no sevoflunme(C);group S1-3 were exposed to 0.003%.0.01% and 0.03% sevoflurane 2 h per day for 5 consecutive days per week for 8 weeks respectively. The mice were then sacrificed at the end of the 8 weeks.The testes and epididymis were emoved and sampled for determination of the activities of total lactic dehydregenase(LDH)and lactic dehydrogenase-X(LDH-X),and the motility rate,amount,and aberration rate of sperm.Testicular uhrastructure were observed by transmission electron microscopy.Results The sperm motifity nne were significantly lower.the sperm aberration rate higher and the activity of LDH-X lower in group S3 than in group C(P<0.05),but there was no significant difference in the above parametem between group SI and group S2(P>0.05).The pathology changed of testes occurred only in group S3 among the 3 groups.Conclusion Long-term exposure to 0.03% sevoflurane can result in the abnormality of the reproductive function in male mice but exposure to≤0.01%sevoflurane dose not.

Obejective To explore the effect of combined use of dexmedetomidine and ultra-low dose naloxone on postoperative hyperalgesia induced by remifentanil. Method 80 ASA gradeⅠ-Ⅱ female patients who were scheduled to perform endoscopic sinus surgery (ESS) were randomly divided into four groups: purely remifentanil group (group R) and remifentanil plus different dosage dexmedetomidine and ultra-low dose naloxone group (group RDN1 ~ RDN3). Then the postoperative VAS on 30 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h together with the firstpostoperative pain time , PCA press numbers , fentanyl usage and adverse reaction rate were recorded and evaluated. Results Average VAS of group R are higher than other groups in all 7 time points at the adjusted significant level of 0.0083, and group R > group RDN1 > group RDN2 > group RDN3, while differences between group RDN2 and RDN3 in all time points are not statistical significant.There is no difference between group RDN1 and group RDN2 inthe first postoperative pain time and the PCA press time at 1h after operation. Difference between group RDN2 and group RDN3 in the PCA press time at 24 h after operation was not significant, and the fentanyl usage of RDN groups are significantly less than group R. Conclusions Combined use of dexmedetomidine and ultra-low dose naloxone induced by remifentanil can improving patients′postoperative hyperalgesia , effect increase with the dose of dexmedetomidine increas , and the increasement is more sensitive in acute pain.

OBJECTIVETo explore the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) combined with Surepath liquid-based cytology test for lung and mediastinal lymphadenopathy.

METHODSEighty EBUS-TBNA cases in West China Hospital of Sichuan University collected from December 2011 to June 2014 were retrospectively analyzed. The conventional smears and Surepath liquid based preparations were reviewed and compared with histological biopsy. Evaluated whether liquid based preparation could improve the satisfactory rate and diagnostic accuracy.

RESULTSThis study included 53 men and 27 women, the male to female ratio was 1.96:1.00; the age ranged from 17 to 79 (mean 54) years. One to four lymph node groups were aspirated in each patient, resulting in a total of 109 lymph node groups, including 57 paratracheal, 34 subcarinal, three tracheal bronchial, seven pulmonary and four hilar lymph node groups. The definite locations of four other mediastinal lymph node groups were not known. The overall satisfactory rate of conventional smears and liquid-based cytology test was 90.0% and 92.5%, respectively. By histology, there were 37 cases diagnosed as malignant tumors, nine as tuberculosis, two as sarcoidosis, 11 as unexplained granulomatous inflammation, and 27 as other benign lesions. The sensitivity, specificity and accuracy of conventional cytological smears for tumors were 86.5%, 97.7% and 92.5% respectively; the positive and negative predictive values were 97.0% and 89.4% respectively. The sensitivity, specificity and accuracy of the liquid-based preparation were 89.2%, 97.7% and 93.8% respectively; the positive and negative predictive values were 97.1% and 91.3% respectively. Combining the conventional cytological smears and liquid based preparation, the sensitivity, specificity and accuracy were 91.9%, 97.7% and 95.0% respectively; and the positive and negative predictive values were 97.1% and 93.3% respectively.

CONCLUSIONSEBUS-TBNA is a good method to diagnose lung and mediastinal lymphadenopathy. Surepath liquid based cytology test could improve the sample satisfactory rate, the diagnostic sensitivity and accuracy. If combined with immunocytochemistry it could be useful for further tumor typing. EBUS-TBNA combined with Surepath liquid based preparation is an effective complement for the histologic biopsy.

Adolescent ; Adult ; Aged ; Biopsy, Fine-Needle ; China ; Female ; Humans ; Immunohistochemistry ; Lung ; diagnostic imaging ; Lung Neoplasms ; diagnostic imaging ; Lymph Nodes ; diagnostic imaging ; Lymphatic Diseases ; diagnostic imaging ; Male ; Middle Aged ; Needles ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography ; Young Adult

Objective:To investigate the predictive value of systemic immune inflammation index (SII) for the overall survival of patients with pancreatic cancer by propensity score matching analysis.Methods:The clinical data of 457 patients with pancreatic cancer admitted to the Affiliated Hospital of Qingdao University from August 2000 to December 2019 were retrospectively analyzed. The age, gender, presence of jaundice, pancreatitis and diabetes, serum CA19-9, total bilirubin level, neutrophil count, platelet count, lymphocyte count in blood, presence of radical surgery, tumor TNM stage, tumor location and the like were recorded. The cut-off value of SII was determined by Youden index. The patients were divided into high and low SII groups accroding to the cut-off value. The propensity score matching was applied to reduce the selection bias of patients. Patients were 1∶2 matched and the caliper value was 0.1. The difference on overall survival between the two groups was compared. The prognostic factors were analyzed by univariate and multivariate Cox regression analysis. Kaplan-Meier was used to draw the overall survival curve to calculate the cumulative survival rate, and the differences between the curves were analyzed by Log-Rank test.Results:The cut-off value of SII was 765. There were statistically significant differences between the high SII group ( n=125) and the low SII group ( n=332) on the presence or absence of pancreatitis, the level of total bilirubin in blood, radical surgery, and TNM stage before the propensity score matching (all P value <0.05). After propensity score matching, there was no statistically significant difference between the high SII group ( n=113) and the low SII group ( n=182) on all the clinical parameters mentioned above except for CA19-9, indicating that the two groups were comparable. Univariate analysis showed that the level of CA19-9, SII, radical surgery and different TNM stage were all related to the overall survival of pancreatic cancer patients. Multivariate analysis showed that high CA19-9 level, high SII, no radical surgery, and worse TNM stage were independent risk factors for short overall survival, and high SII ( HR=1.882, 95% CI 1.446-2.450, P<0.001) was significantly associated with poor prognosis. The overall survival of patients with high SII was obviously shorter than the low SII group ( P<0.001), and the average survival time of patients with high and low SII were 8.86 and 11.38 months, respectively. Conclusions:SII is of great value in evaluating the overall survival of pancreatic cancer patients. Higher SII is associated with shorter overall survival.

ObjectiveTo explore the mechanism of Dihuang Yinzi （DHYZ）in improving astrocyte injury in the brain and regulating energy metabolism and autophagy disorder in Alzheimer's disease （AD） model mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + DHYZ group （2.5 g·kg^-1）， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + DHYZ group （2.5 g·kg^-1）， with 20 mice in each group. The mice in the control group and the model group were administered with an equal volume of sterilized normal saline by gavage， once a day for 150 days. Novel object recognition test and step-down test were performed to evaluate the learning and memory ability of mice. The expression of glial fibrillary acidic protein （GFAP） in astrocytes was detected by immunofluorescence and Western blot. High-performance liquid chromatography （HPLC） was used to detect adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in brain tissues of mice， and the data obtained were used to calculate energy charge （EC） levels. The phosphorylation levels of liver kinase B1 （LKB1）， adenosine 5′-monophosphate （AMP）-activated protein kinase （AMPK）， UNC-51-like kinase 1 （ULK1）， and mammalian target of rapamycin （mTOR） and the expression levels of autophagy-related proteins Beclin-1， microtuble-associated protein 1 light chain 3 （LC3）-Ⅱ/LC3-Ⅰ， and p62 in mouse brain were measured by Western blot. ResultCompared with the control group， the model group showed decreased novel object recognition index， shortened retention latency， increased error times in the step-down test， up-regulated protein expression of GFAP， decreased content of ATP， ADP， and EC in brain tissues， elevated AMP ， increased levels of p-AMPK， p-LKB1， and p-mTOR， and protein expression of p62 ， and down-regulated p-ULK1 level and protein expression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ（P<0.01）， while the above experimental indexes were not significantly different in the control + DHYZ group. Compared with the model group， the model + DHYZ group showed increased novel object recognition index（P<0.05）， prolonged retention latency（P<0.01）， decreased error times（P<0.01） in the step-down test， reduced protein expression of GFAP（P<0.05）， increased content of ATP， ADP， and EC in brain tissues （P<0.05， P<0.01）， decreased AMP content（P<0.05）， reduced p-AMPK， p-LKB1， and p-mTOR levels and protein expression of p62， and up-regulated p-ULK1 level and protein expression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ（P<0.01）. ConclusionBy protecting astrocytes， DHYZ can improve energy metabolism and autophagy disorder in AD mice to improve the learning and memory ability of model mice.

ObjectiveTo investigate the mechanism of Dihuang Yinzi in improving astrocyte injury and protecting synaptic structure and function in the brain of Alzheimer's disease （AD） mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. The mice in the control + Dihuang Yinzi group and the model + Dihuang Yinzi group were administered with Dihuang Yinzi by gavage， and those in the control group and the model group received an equal volume of sterilized normal saline， once a day for 150 days. The learning and memory ability of mice was tested by the light-dark box test and Y-maze spontaneous alternation test. The content of glutamate （Glu） and glutamine （Gln） was measured by liquid chromatography-tandem mass spectrometry （LC-MS）. Long-term potentiation （LTP） assay was used to detect synaptic plasticity in brain tissues. The protein expression levels of excitatory amino acid transporter 2 （EAAT2）， postsynaptic density protein95 （PSD95）， and synaptophysin （SYN） in brain tissues were measured by Western blot. Immunofluorescence was used to assess the localization and expression of EAAT2. Colorimetry was performed to detect Na⁺-K⁺ ATPase activity in mouse brain tissues. ResultAs compared with the control group， the model group showed shortened residence latency （P<0.01）， increased number of errors （P<0.01） in the light-dark box test， reduced spontaneous alternation behaviors （P<0.01）， no significant difference in the total number of arm entries in the Y-maze spontaneous alternation test， down-regulated expression of EAAT2， PSD95， and SYN （P<0.01）， blunted activity of Na⁺-K⁺ ATPase （P<0.01）， up-regulated Glu level （P<0.01）， down-regulated Gln level （P<0.01）， and reduced relative population spike （PS） amplitude and the slope of excitatory postsynaptic potential （EPSP） （P<0.05， P<0.01）， while the above experimental indexes were not significantly different in the control + Dihuang Yinzi group. Compared with the model group， the model + Dihuang Yinzi group displayed prolonged residence latency （P<0.05）， decreased number of errors （P<0.01） in the light-dark box test， increased spontaneous alternation behaviors （P<0.01）， no significant difference in the total number of arm entries in the Y-maze spontaneous alternation test， up-regulated expression of EAAT2， PSD95， and SYN （P<0.01）， potentiated activity of Na⁺-K⁺ ATPase （P<0.01）， reduced Glu level （P<0.01）， up-regulated Gln level （P<0.01）， and increased PS amplitude and EPSP slope （P<0.01）. ConclusionDihuang Yinzi can improve cognitive dysfunction in AD mice by protecting astrocytes， increasing Glu uptake to reduce its abnormal accumulation， and protecting synaptic structure and function.