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Objective:To investigate the influencing factors for synchronous colorectal liver metastasis (synCRLM).Methods:The retrospective case-control study was conducted. The clinicopathological data of 3 172 patients with primary colorectal cancer (CRC) who were admitted to the Affiliated Hospital of Qingdao University from January 2010 to January 2016 were collected. There were 1 946 males and 1 226 females, aged (63±12)years, with a range from 21 to 97 years. Observation indicators: (1) general data analysis; (2) clinicopathological data analysis; (3) analysis of influencing factors for synCRLM. Measurement data with normal distribution were represented as Mean±SD. Count data were represented as absolute numbers. The influencing factors for synCRLM were analyzed after excluding missing data of tumor differentiation degree, tumor diameter, pathological T stage and N stage. Univariate analysis was conducted by chi-square test or Logistic regression model. Multivariate analysis was conducted by Logistic regression model. Results:(1) General data analysis: among the 3 172 patients, cases with age ≤29 years, from 30 to 39 years, from 40 to 49 years, from 50 to 59 years, from 60 to 69 years, from 70 to 79 years, and ≥80 years were 15, 82, 342, 774, 965, 759 and 235, respectively. There were 2 972 patients in Qingdao, 172 cases in Yantai and 28 cases in Weihai. Of the 2 972 patients in Qingdao, there were 422 cases in Shinan District, 658 cases in Shibei District, 457 cases in Huangdao District, 144 cases in Laoshan District, 188 cases in Licang District, 205 cases in Chengyang District, 252 cases in Jimo District, 221 cases in Jiaozhou City, 255 cases in Pingdu City, 170 cases in Laixi City. (2) Clinico-pathological data analysis: among the 3 172 patients, there were 1 639 cases of colon cancer including 972 cases with left colon cancer and 667 cases with right colon cancer, 1 533 cases of rectal cancer. There were 2 981 cases of adenocarcinoma, 165 cases of mucinous adenocarcinoma, 10 cases of signet ring cell carcinoma and 16 cases of other types including carcinoid tumor, squamous carcinoma, tubular adenocarcinoma, etc.There were 162 cases with highly differentiated adenocarcinoma, 5 cases with highly-moderately differentiated adenocarcinoma, 2 338 cases with moderately differentiated adenocarcinoma, 80 cases with moderately-poorly differentiated adeno-carcinoma, 396 cases with poorly differentiated adenocarcinoma and 191 cases missing tumor differentiation data. There were 708 cases with tumor diameter <4 cm, 1 957 cases with tumor diameter ≥4 cm and 507 cases missing tumor diameter data. There were 486 cases in T1 or T2 stage of pathological T stage, 2 169 cases in T3 or T4 stage of pathological T stage and 517 cases missing tumor pathological T staging data. There were 1 563 cases in N0 stage of pathological N staging, 1 062 cases in N1 or N2 stage of pathological N staging and 547 cases missing tumor pathological N staging data. There were 2 895 cases without synCRLM and 277 cases with synCRLM. There were 2 799 cases without diabetes and 373 cases with diabetes. There were 2 931 cases without fatty liver and 241 cases with fatty liver. There were 2 989 cases negative for hepatitis B surface antigen (HBsAg) and 183 cases positive for HBsAg. (3) Analysis of influencing factors for synCRLM. Results of univariate analysis showed that gender, tumor location, tumor differentiation degree, tumor diameter, pathological T stage, fatty liver, HBsAg were related factors for synCRLM in primary colorectal cancer ( χ2=7.400, 7.577, 7.111, 4.513, 12.125, 5.686, 5.919, P<0.05), and neutrophils counts, lymphocytes counts, platelet counts, alanine aminotransferase (ALT), aspartate aminotrans-ferase (AST), total bilirubin, γ-glutamyltransferase (GGT), triacylglycerol (TG), total cholesterol (TC), carcinoembryonic antigen (CEA), and CA19-9 were related factors for synCRLM in primary colorectal cancer ( odds ratio=1.101, 0.807, 1.002, 1.017, 1.023, 1.027, 1.012, 0.686, 1.169, 1.007, 1.004, 95% confidence interval as 1.048-1.156, 0.678-0.960, 1.001-1.004, 1.011-1.024, 1.016-1.031, 1.011-1.044, 1.009-1.015, 0.541-0.869, 1.047-1.306, 1.006-1.008, 1.003-1.004, P<0.05). Results of multivariate analysis showed that cases as male, case with positive HBsAg, AST, GGT, TC, CEA and CA19-9 were independent risk factors for synCRLM in primary colorectal cancer ( odds ratio=1.503, 2.492, 1.018, 1.007, 1.301, 1.005, 1.003, 95% confidence interval as 1.038-2.178, 1.443-4.304, 1.003-1.034, 1.003-1.011, 1.112-1.522, 1.003-1.006, 1.002-1.003, P<0.05), and lymphocytes, ALT and TG were independent protective factors for synCRLM in primary colorectal cancer ( odds ratio=0.777, 0.983, 0.602, 95% confidence interval as 0.608-0.993, 0.966-0.999, 0.421-0.862, P<0.05). Conclusion:Cases as male, case with posotive HBsAg, AST, GGT, TC, CEA and CA19-9 are independent risk factors for synCRLM in primary colorectal cancer, while lymphocytes, ALT and TG are independent protective factors for synCRLM in primary colorectal cancer.

ObjectiveTo investigate the effect of ulinastatin on perioperative renal function in patients undergoing orthotopic liver transplantation.MethodsSixty ASA Ⅱ or Ⅲ patients of both sexes aged 35-64 yr weighing 50-75 kg with normal blood urea nitrogen (BUN) and creatinine (Cr) before operation undergoing orthotopic liver transplantation were randomly divided into 2 groups ( n ＝ 30 each):control group (group C) and ulinastatin group ( group U).Anesthesia was induced with midazolam,fentanyl,etomidate and vecuronium and maintained with isoflurane inhalation,propofol TCI,continuous remifentanil infusion and intermittent iv boluses of fentanyl and vecuronium.The patients were tracheally intubated and mechanically ventilated.PET CO2 was maintained at 30-35 mm Hg.Ulinastatin 400 000 IU in normal saline 20 ml was infused iv after induction of anesthesia.Ulinastatin 200 000 IU was then infused every 4 h until 48 h after operation.Urine volume and the amount of furosemide administered were recorded before anhepatic phase,and during anhepatic and neohepatic phase.Venous blood samples and urine were collected before induction of anesthesia (T1),at 15 min of anhepatic phase ( T2 ),at 15min of neohepatic phase (T3),at the end of operation (T4) and 48 h after operation (T5) for determination of serum concentrations of BUN,Cr and creatinine clearance rate and urinary N-acetyl-beta-D-glucosaminidase (NAG)activity and microalbumin concentration.ResultsCompared with group C,ulinastatin significantly decreased the amount of furosemide administered and increased urine volume during anhepatic and neohepatic phase,decreased serum Cr concentration,increased creatinine clearance rate at T2.5,decreased urinary NAG activity and microalbumin concentration at T4.5 and serum BUN concentration at T3-s.ConclusionUlinastatin has protective effect on rehal function during perioperative period in patients undergoing orthotopic liver transplantation.

An LC-MS/MS method was developed to investigate the pharmacokinetic parameters in healthy Chi-nese volunteers following single and multiple oral administration of dimemorfan phosphate. In the Single-dose study,two-period and crossover study was conducted in 12 healthy volunteers,which were administered with single-dose of 10 mg or 40 mg of dimemorfan phosphate. And another 12 volunteers were administered with 20 mg. The values of AUC0-48 h,t1/2,and cmax were (11. 81 ±14. 46),(52. 60 ±96. 01 )and (34. 70 ±29. 59)ng. h/mL,(12. 11 ±2. 54),(12. 16 ±2. 01)and (12. 77 ±1. 27)h,and (0. 9653 ±0. 8178),(3. 150 ±3. 451)and (2. 167 ±1. 650)ng/mL for 10 mg,40 mg and 20 mg oral administration. The same 12 healthy volunteers as the group of single-dose of 20mg were participated in multiple-dose study,which were administered dimemorfan phos-phate 20 mg,three-time a day until the day-8,showed AUC0-48 h,t1/2,and cmax were (115. 9 ±135. 2)ng.h/mL, (11. 22 ±1. 61)h,and (7. 418 ±7. 010)ng/mL. The accumulation parameter Rcmax and RAUC was (3. 14 ±1. 34) and (3. 38 ±1. 22),respectively. Dose proportional of cmax and AUC was not concluded ranging from 10 mg to 40 mg after confidence interval criteria method. An accumulation was occurred after multiple -dose administra-tion with the consequence. And the results demonstrated significant individual difference.

Objective To explore the transfection efficiency of primary lymphocytes from human peripheral blood by different methods to acquire the method with higher transfection efficiency.Methods Mononuclear cells from human peripheral blood were isolated using Ficoll-Hypaque.Cell viability was detected by Trypan blue staining.Suspending lymphocytes were sucked out and were incubated in 24-well plate after cultured in 6-well plate for 2 h.Activated lymphocytes were transfected by electroporation with plasmid(PEGFP-N1).Resting or activated lymphocytes were transfected by lentivirus vector(LVGFP) single infection or repeated infection,respectively.Green fluorescence protein (GFP) was detected under the fluorescence microscopy and percentage of positive cells was checked by flow cytometry at different time points after infection.At the same time,the effectiveness of lentivirus infection was compared under different conditions.Results Purity of mononuclear cells isolated by Ficoll-Hypaque was 95 ％ and its viability was over 95 ％.The percentage of lymphocytes obtained with a uniform shape was 90 ％-95 ％.Scattered fluorescence was observed by electroporation under the conditions of voltage 2 100 V,pulse width 10 ms,pulse number 1 for lymphocyte,while fluorescent became weaker over time and no green fluorescent was observed after transfection for 72 h.After resting lymphocytes were infected once for 48 h by lentivirus vector,green fluorescent was not found and positive cells were less than 1％.1％-5 ％ of activated lymphocytes could express GFP after single lentivirus infection and the expression levels were enhanced with concentration increasing,while 5 ％-10 ％ of activated lymphocytes showed strong green fluorescent by repeated lentivirus infection.In contrast with electroporation,the fluorescent with lentivirus infection was stronger over time.Conclusion Repeated lentivirus infection could efficiently transfect exogenous genes into activated lymphocytes for stable expression.

Objective To investigate the role of receptor for advanced glycation end - products nuclear factor - κB(RAGE - NF - κB)signaling pathway in the lipopolysaccharide - induced acute lung injury(ALI)in neo-natal rats. Methods Thirty - two SD rats were divided into 4 groups by complete randomization method(8 cases in each group).(1)Lipopolysaccharide(LPS)group was given intraperitoneal injection of 9 g/ L saline and 3 mg/ kg LPS 1 h later.(2)Bortezomib group was given intraperitoneal injection of Bortezomib(0. 2 mg/ kg)and 3 mg/ kg LPS 1 h later.(3)Anti - RAGE mAb group was given intraperitoneal injection of anti - RAGE mAb(15 mg/ kg)and 3 mg/ kg LPS 1 h later.(4)Control group was given 9 g/ L saline was given at each time point. All the rats were sacrificed and observed 24 h later. Levels of tumor necrosis factor(TNF) - α in the plasma and bronchoalveolar lavage fluid(BALF) were detected by enzyme linked immunosorbent assay. RAGE and NF - κB levels in tissue homogenates were detected by Western blot and mRNA levels were detected by reverse transcription - polymerase chain reaction. The pathological assessment of the lung tissues was performed by HE staining. Results (1)Among 4 groups,there were significantly differences in TNF - α in serum and BALF(F = 150. 70,P ﹤ 0. 001;F = 165. 83,P ﹤ 0. 001). Levels of TNF - α in LPS group were significantly higher than those of two pretreatment groups(all P ﹤ 0. 05).(2)Western blot figures il-lustrated that the concentrations of RAGE mRNA and NF - κB in anti - RAGE mAb group and bortezomib group were lower than those of the LPS group.(3)Reverse transcription - polymerase chain reaction analysis showed that there were significant differences in the expression of RAGE mRNA and NF - κB mRNA among 4 groups(F = 175. 14,P ﹤0. 05;F = 188. 65,P ﹤ 0. 05). Levels of RAGE mRNA and NF - κB mRNA in the LPS group were significantly higher than those of two pretreatment groups(all P ﹤ 0. 05).(4)Lung injury score differences among 4 groups were statistical-ly significant(F = 106. 01,P ﹤ 0. 001). Pathological changes in two pretreatment groups reduced compared to those of the LPS group(all P ﹤ 0. 05). Conclusions RAGE - NF - κB signaling pathway regulates the LPS - induced ALI in neonatal rats. Anti - RAGE mAb and Bortezomib both have a protective effect on LPS - induced ALI.

Objective To discuss the application value of shear wave elastography (SWE) and superb microvascular imaging (SMI) in pathological grading of breast invasive ductal carcinoma (IDC).MethodsSixty patients with breast tumor were selected,which were totally 64 lesions.Before operation,SWE and SMI pattern were started to detect the lesions.And images in SWE and SMI pattern were saved.All lesions were proved to be IDC and pathological gradings were got according to the pathological result.The mean of Young′s modulus(AveT1) and maximum of Young′s modulus(AveT2) were recorded in SWE pattern,and degree of blood was recorded in SMI pattern followed Adler′s grading standard.Then differences of AveT1,AveT2 and degree of blood in different pathological grading of invasive ductal carcinoma were evaluated.Results ①In pathological grading 1 group,the average of AveT1 was (62.1±10.4)kPa,and the average of AveT2 was (93.0±20.1)kPa.In pathological grading 2 group,the average of AveT1 was (79.8±8.6)kPa,and the average of AveT2 was (120.6±18.7)kPa.In pathological grading 3 group,the average of AveT1 was (92.6±12.1)kPa,and the average of AveT2 was (137.3±21.5)kPa.The AveT1 and AveT2 were gradually growing with higher pathological grading of breast invasive ductal carcinoma,which were statistically significant (P<0.05).②In pathological grading 1 group,there were 7 cases in the degree of blood 0-Ⅰ and 14 in the degree of blood Ⅱ-Ⅲ.In pathological grading 2 group,there were 3 cases in the degree of blood 0-Ⅰ and 18 cases in the degree of blood Ⅱ-Ⅲ.In pathological grading 3 group,there were only 1 case in the degree of blood 0-Ⅰ and 21 cases in the degree of blood Ⅱ-Ⅲ.There were more lesions of rich blood with higher pathological grading of breast invasive ductal carcinoma,which was statistically significant (P<0.05).Conclusions There are differences of elastography and degree of blood in different pathological grading of breast invasive ductal carcinoma,SWE and SMI can prompt pathological grading and provide important clinical reference value.

Objective To explore the relationship of monocyte chemoattractant protein-1(MCP-1)and oxygen-induced retinopathy(OIR).Methods Thirty-six newborn SD rats were divided into 2 expanded litters,18 of which were exposed to 50 mL/L oxygen and then 10 mL/L oxygen in alternating 24-hour periods(experiment group),an additional 18 rats as control rats were raised simultaneously in room air(control group).On postnatal 14 days(P14),oxygen-exposed rats were removed to room air.The eyeballs of 6 rats from each group were enucleated and fixed by formaldehyde at postnatal 14 days(P14),postnatal 17 days(P17),and postnatal 21 days(P21)respectively,and then cross sectioned.The nuclei of proliferative retinal vessels were counted through the crosssections to measure the average retinal capillary density index(RCDI)when stained with hematoxylin and eosin(HE)under light;the expression of MCP-1 was measured by immunohistochemistry.Results There existed obviously differencc between 2 groups in the field of both RCDI and the expression of MCP-1 at the same time point [t(P14)=6.69 P=0.001,t(P17)=3.43 P=0.006,t(P21)=2.37 P=0.039;t(P14)=40.45,t(P17)=43.44,t(P21)=17.45 Pa=0],when RCDI and the expression of MCP-1 were compared among the different time points with in the same group,there existed obviously difference among three time points in the experiment group(F=17.74 P=0.0001;F=421.5 P=0),but no differencc in control group(F=0.016 P=0.984;F=0.006 P=0.994).There existed positive correlation between the expression of MCP-1 and the value of RCDI in experiment group(r=0.822 P=0).Conclusions Neovascularization resulting from OIR occurs before room air recove-ry.MCP-1 is upregulated and subsequently downregulated in OIR.Neovascularization in the OIR model appear to be associated with increased retinal MCP-1.

Objective To explore the pathological changes of the livers from hepatic failure (HF)patients and its association with clinical disease stages.Methods Thirty-nine patients with liver failure caused by HBV infections were investigated,and none accompanied with hepatocellular carci- noma.The sections of tissue were taken from the liver after liver transplantation and stained with he- matoxylin eosin(H&E)or RT(reticular fiber)staining.The pathological features were analyzed and compared between the clinical and pathological diagnosis.Results 1.The range and the grade of the pathological changes were all well-proportioned in the whole liver but quite asymmetrical in the same spicemen.2.4 cases with clinical diagnosis of cirrhosis(active stage)were in accordance with the pathological diagnosis.Only 17 in 35cases can be pathologically diagnosed as chronic severe hepatitis (SH),while the other 18 cases were pathologically diagnosed as cirrhosis(active stage).Conclu- sion There were a great inconsistency between the clinical and pathological diagnosis.

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