Integrins are a family of transmembrane receptors that connect the extracellular matrix and actin skeleton, which mediate cell adhesion, migration, signal transduction, and gene transcription. As a bi-directional signaling molecule, integrins can modulate many aspects of tumorigenesis, including tumor growth, invasion, angiogenesis, metastasis, and therapeutic resistance. Therefore, integrins have a great potential as antitumor therapeutic targets. In this review, we summarize the recent reports of integrins in human hepatocellular carcinoma (HCC), focusing on the abnormal expression, activation, and signaling of integrins in cancer cells as well as their roles in other cells in the tumor microenvironment. We also discuss the regulation and functions of integrins in hepatitis B virus-related HCC. Finally, we update the clinical and preclinical studies of integrin-related drugs in the treatment of HCC.
Humans ; Integrins/metabolism* ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Cell Adhesion ; Carcinogenesis ; Cell Transformation, Neoplastic ; Tumor Microenvironment

Objective To analyze the etiology and prognosis of severe complications of percutaneous nephrolithotomy (PCNL).Methods The clinical data of patients with severe complications after PCNL from December 2004 to December 2015 were retrospectively analyzed.Age of the patients ranged from 25 to 69 years old,with an average of 41 years.There were 64 cases with 29 male and 35 female.Fifty-five cases were diagnosed as renal calculi,including 21 cases of left renal calculi,19 cases of right renal calculi;15 cases of bilateral renal calculi;2 cases of the patients were bilateral upper ureteral calculi;7 patients were renal calculi upper ureteral calculi on the other side.In all cases,the maximum diameter of calculus was 1.8-4.3 cm (mean 2.6 cm) and hydronephrosis depth was 0-5.9 cm (mean 2.3 cm);15 cases were previously treated with nephrolithotomy.The modified Clavien grading system was used to evaluate surgical complications,and ≥grade Ⅲ complications were considered as serious complications.Results Among the 64 cases,28 cases were classified as Clavien Ⅲ class.There were 2 cases of bleeding in operation due to renal parenchyma laceration or multiple access,patients were treated with later open surgery.Postoperative bleeding were revealed in 22 cases,16 of which were hemorrhage from the nephrostomy tubes,4 of which complained of discontinuity gross hematuria and 2 postoperative bleeding were encountered during the nephrostomy tube remove.All the cases received renal arteriography and were diagnosed with pseudoaneurysm,bleeding were stopped after embolization.3 cases of pleural injury were treated with closed thoracic drainage,1 colon injury was treated with open colostomy.There were 32 cases of urinary sepsis considered as Clavien Ⅳ complications,and these patients were transferred to the Intensive Care Unit.Clavien Ⅴ class 4 cases:1 died of hemorrhagic shock due to pleural injury,2 cases died of urinary sepsis and multiple organ failure and another case died of pulmonary embolism.Conclusions PCNL has high risk of serious complications,which should be always strictly follow the principles.Adequate preoperative preparation,appropriate surgery access,carefully and gently operate,appropriate antibiotic use and postoperative management are the key measures to reduce the incidence of complications.

OBJECTIVE:To study the alleviation effect of nervonic acid on movement disorder of model mice with Parkinson's disease(PD). METHODS:Mice were randomly divided into blank control group(normal suline),model group(normal saline), Levodopa and benserazide hydrochloride tablet group (positive control,calculated by L-dopamine 120 mg/kg),nervonic acid low-dose,medium-dose,high-dose groups(20.0,40.0,80.0 mg/kg),10 in each group. Except for blank control group,mice in other groups were inducced for PD models. After modeling,mice were intragastrically given relevant medicines,once a day,for 14 d. After the last administration,behavioral changes of mice in each group were observed. HPLC was conducted to detect dopa-mine(DA)and its metabolites dihydroxybenzoic acid(DOPAC),homovanillic acid(HVA)concentrations in the striatum of mice. RESULTS:Compared with blank control group,climbing time was extended in model group,drum time was shortened,spontane-ous movement times was decreased,and DA,DOPAC,HVA contents in the striatum were reduced (P<0.05). Compared with model group,climbing time was shortened in Levodopa and benserazide hydrochlo ride tablet group,nervonic acid dose groups, drum time was extended,and DA,DOPAC,HVA contents in the striatum were increased(P<0.05);and spontaneous movement times was increased in Levodopa and benserazide hydrochloride tablet group,and nervonic acid high-dose group(P<0.05). CON-CLUSIONS:Nervonic acid can effectively improve symptoms of movement dysfunction of model mice with PD. The mechanism may associate with increasing DA content in the striatum.

OBJECTIVE: To analyze chromosome damage and its possible influencing factors in patients with occupational chronic benzene poisoning. METHODS: Fifty patients with occupational chronic benzene poisoning were selected as chronic benzene poisoning group,and 53 workers without occupational exposure to benzene and other toxic substances were chosen as control group by using convenience sampling method. Questionnaire and routine blood test were conducted on all study subjects. Micronucleus rate test was performed by micronucleus blocking cytokinesis assay. RESULTS: Peripheral blood tests of chronic benzene poisoning group showed significantly reduced hemoglobin level,counts of red blood cells,white blood cells,platelets,lymphocytes and neutrophils( P < 0. 01),and higher lymphocyte micronucleus rates compared to control group( !: 6. 26‰ vs 3. 91‰,P < 0. 01). The proportion of increased lymphocyte micronucleus rate in chromic benzene poisoning group was also higher than that in control group( 46. 0% vs 5. 7%,P < 0. 01). The multivariate Poisson analysis results indicated that the time after disengagement from benzene exposure was the influencing factor of micronucleus rate in chronic benzene poisoning group( P < 0. 05),after adjusting the confounding factors of gender,age,smoking status,alcohol drinking status and working age of benzene exposure. CONCLUSION: Occupational chronic benzene poisoning leads to increase of chromosome damage in lymphocytes of patients. The time after disengagement from benzene exposure was positively correlated with chromosome damage.

Objective To investigate the molecular mechanisms of glial cell derived neurotrophic factor in promoting proliferation of spermatogonial stem cell.Methods RNAi expression vectors,targeted at GDNF,were constructed and transfected into SSCs from 5 to 7 days old mice.The SSCs with highest effectiveness of GDNF interfere was set as study group.And the SSCs without GDNF interfere was considered as control group.The ELISA method was used to compare the proliferative rate between study group and control group.Flow cytometry,RT-PCR were used to detect the expression of GDNF,RTKs,Fyn and FAK's mRNA,and the apoptosis of SSCs.Results From 1 to 4 days after transinfection,the absorbable A value in study group was 0.45 ± 0.02,0.68 ± 0.03,1.12 ± 0.03,2.24 ± 0.04,respectively.Meanwhile,the same item in control group was 0.46 ± 0.03、0.73 ± 0.02、1.32 ± 0.05、1.15 ± 0.06,respectively (P ＜ 0.05).There were significant different between experiment groups (25.43 ± 1.91) ％ and control group (5.61 ± 0.16)％ in the apoptosis rates of SSCs (P ＜ 0.05).Significant differences were noted between experimental group and control group(P ＜ 0.05).The mRNA expression rates of GDNF was (12.32 ± 1.22) ％ in study group and (54.25 ± 1.34)％ in control group (P ＜0.01).The mRNA expression rates of RTKs and Fyn and FAK in study group and control group were (16.24 ± 1.35)％ vs (45.35 ± 1.37)％,(18.32 ±1.34)％ vs (38.37 ± 1.55)％,(20.04 ± 1.65)％ vs (43.27 ± 1.28)％,respectively (P ＜0.05).Conclusions The glial cell line derived neurotrophic factor was important in course of SSCs' proliferation,which may up-regulating the expression of RTKs,Fyn and FAK.

Objective To explore the application value of end-to-side closed in situ pancreaticojejunostomy in pancreaticoduodenectomy.Methods The clinical data of 22 patients with obstructive jaundice who were admitted to the Second Affiliated Hospital of Harbin Medical University from January to March 2014 were retrospectively analyzed.All the patients were explored whether tumors invaded inferior vena cava, superior mesenteric vein and portal vein after gallbladder decompression under general anesthesia by tracheal intubation.The standard or extended pancreaticoduodenectomy was applied according to the intraoperative results.The method of pancreaticojejunostomy was end-to-side closed in situ anastomosis of pancreatic duct and jejunal seromuscular layer.The operation time, intraoperative blood loss, postoperative gastrointestinal function recovery time, amylase concentration of drainage at postoperative day 1,3,5, postoperative complication, pathological classification and duration of hospital stay were observed.Patients were followed up by outpatient examination and telephone interview till May 2014.The out-patient follow-up included color Doppler ultrasound examination of effusion near the pancreatic stump, and the telephone interview included whether there were diarrhea of exocrine pancreatic insufficiency.Measurement data with normal distribution were presented as-x ± s (range) , and measurement data with skewed distribution as M(range).Results All the 22 patients underwent successfully the operation, including 17 undergoing standard pancreaticoduodenectomy and 5 undergoing extended pancreaticoduodenectomy, with end-to-side closed in situ anastomosis of pancreatic duct and jejuna seromuscular layer.The operation time of pancreaticoduodenectomy and end-to-side closed in situ pancreaticojejunostomy were (313 ± 37)minutes (range, 228-360 minutes) and(13 ± 4) minutes (7-22 minutes) , respectively.The intraoperative blood loss was (400 ± 207) mL (range, 100-800 mL).The mean tumor size was 3.69 cm2(range, 0.72-1.68 cm2).The recovery time of gastrointestinal function was (5 ±2)days (range, 4-7 days).The serum amylase at postoperative day 1, 3, 5 in the 21 patients was (145±30)U/L (range, 116-180 U/L), (136±40)U/L (range, 105-176 U/L), (147 ±38)U/L(range, 110-175 U/L), and the drainage amylase was (220 ±56)U/L (range, 172-289 U/L), (240 ±54)U/L (range, 192-300 U/L) , (245 ± 52) U/L (range, 190-298 U/L) , respectively.The serum amylase at postoperative day 1, 3, 5 in the patient with pancreatic fistula was 156 U/L, 178 U/L and 177 U/L, and the drainage fluid amylase was 500 U/L, 620 U/L and 605 U/L, respectively.There was 1 patient in the 22 patients with pancreatic duct stent and without death.Among the 4 patients with postoperative complications, 1 patient with grade A postoperative pancreatic fistula recovered after continuous external drainage, the other 3 including 1 case of infection,1 case of pneumonia and 1 of stress ulcer bleeding also recovered after symptomatic and supportive treatment.Postoperative pathological examinations of the 22 patients showed 12 cases of ductal adenoeareinoma, 2 of neuroendocine tumors, 1 of simple cyst, 1 of cystadenocarcinoma, 1 of squamous carcinoma, 1 of adenocarcinoma, 1 of ampullary carcinoma, 1 of tubular adenoma, 1 of leiomyoma and 1 of atypical intraductal hyperplasia.The average length of hospital stay was (11 ±3)days (range, 2-15 days).There were no effusion near the pancreatic stump showed in color Doppler ultrasound examination and diarrhea of exoerine pancreatic insufficiency.Conclusion End-to-side closed in situ pancreaticojejunostomy is safe and feasible, and can be applied to any pancreatic duct size and texture.

Objective To investigate the clinical outcomes derived from Ningmitai combined with tamsulosin to prevent double-J stent syndrome after laser lithotripsy with ureteroscope. Methods 117 patients underwent laser lithotripsy with ureteroscope and then placed a double-J stent for draining were collected from January 2010 to January 2013. Patients with double-J stent placement were divided into four groups determined by dosage regimen. Tamsulosin group (30 cases) was treated with tamsulosin (0.4 mg once daily) lonely, Ningmitai group (29 cases) was treated with Ningmitai (1.52 g, trice time a day) lonely, tamsulosin combined Ningmitai group (30 cases) was treated with tamsulosin and Ningmitai at the same time, operation control group (28 cases) was neither tamsulosin nor Ningmitai. The catheter was removed on the 3rd day post-lithotripsy and then remained double-J stent for 1 month. The scores of urinary tract, pain and the incidence of gross hematuria were assessed. Results The significant differences in the improvement of symptom score (χ2=22.038, P=0.000), pain score (χ2=9.876, P=0.020) and hematuria (χ2=8.000, P=0.046) were found among tamsulosin group, Ningmitai group, and tamsulosin combined Ningmitai group. The number of patients with symptomless, slight symptom in tamsulosin combined Ningmitai group were higher than those of tamsulosin group, Ningmitai group, operation control group (symptomeless:14 vs. 6, 3 and 2 cases;slight symptom:13 vs. 9, 5, 4 cases). The number of patients with>Ⅱpain score (7 vs. 9, 14, 17 cases) and incidence of hematuriag [26.6%(8/30) vs. 56.7%(17/30), 58.6% (17/29), 53.6% (15/28)] were lower in tamsulosin combined Ningmitai group than those of tamsulosin group, Ningmitai group, operation control group. The drug combination of Ningmitai with tamsulosin had the synergism to relived symptom and pain, and showed the more obviousthan lonely use. Conclusion The drug combination of Ningmitai with tamsulosin can be used in clinic for prophylactic purpose to prevent double-J syndrome.

China ; Humans ; National Health Programs ; standards ; statistics & numerical data ; United Kingdom

OBJECTIVETo evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride (VC)-induced chromosomal damage in peripheral lymphocytes.

METHODSIn this study, 317 workers occupationally exposed to VC were recruited from a factory in Shandong Province, China. The micronucleus (MN) frequency in peripheral lymphocytes was used as an indicator of chromosomal damage. Polymerase chain reaction-restriction fragment length polymorphism and created restriction site combined with restriction fragment length polymorphism were used to determine the five single nucleotide polymorphisms in XRCC1 and APE1 genes in the base excision repair pathway. The association of chromosomal damage with these polymorphisms and the haplotype of XRCC1 was analyzed using Poisson regression and PHASE 2.0.2.

RESULTSIt was found that among the VC-exposed workers, individuals with XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) had a significantly higher MN frequency than those with homozygous wild-type genotypes, with frequency ratios (FR) as follows, respectively: FR = 1.21, 95%CI: 1.05∼1.39 (P < 0.05); FR = 1.14, 95%CI: 1.00∼1.38 (P < 0.05); FR = 1.26, 95%CI: 1.11∼1.44 (P < 0.05); FR = 1.23, 95%CI: 1.08∼1.46 (P < 0.05). APE1 Asp148Glu was found of no significant relationship with MN frequency. Haplotype analysis of XRCC1 demonstrated that the MN frequencies in subjects with CTAA/CTAA and CCAA/CTAA were significantly higher than that in those with TCGG/TCGG (FR = 1.19, 95%CI: 1.02∼1.32, P < 0.05; FR = 1.41, 95%CI: 1.02∼1.87, P < 0.05). Furthermore, association was found between accumulated exposure to VC and XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) after adjustment for age, sex, drinking, and smoking.

CONCLUSIONVC can induce chromosomal damage even when the exposure level is lower than the national occupational health standard of China (PC-TWA: 10 mg/m(3)); the polymorphisms in XRCC1 and APE1 are associated with chromosomal damage induced by VC.

Adult ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Haplotypes ; Humans ; Male ; Micronuclei, Chromosome-Defective ; Middle Aged ; Occupational Exposure ; adverse effects ; Polymorphism, Restriction Fragment Length ; Vinyl Chloride ; poisoning ; X-ray Repair Cross Complementing Protein 1 ; Young Adult

Objective To compare the safety and efficacy of the 2μm laser and the bipolar electrotome used in transurethral re-section of bladder tumor(TURBT)for treating non-muscle invasive bladder cancer(NMIBC).Methods The clinical data in the pa-tients with NMIBC treated by TURBT in our hospital from March 2009 to May 2013 were retrospectively analyzed.All patients were divided into the 2μum laser group(n=89)and the bipolar electrotome group(n=82).The operation time,complications,post-operative hospital stay and recurrence rate were compared between the two groups.Results There were no statistically significant differences in the operation time,postoperative hospital stay and recurrence rate between the two groups(P>0.05).Compared with the 2 μm laser group,the bipolar electrotome group showed significantly higher occurrence rate of the obturator nerve reflex (20.7%vs.0,P<0.05)and the bladder perforation(7.3% vs.0,P<0.05)and longer postoperative bladder irrigation time [(3.1±0.9)d vs.(2.2±1.0)d,P<0.05],the differences between the two groups had statistical significance.Conclusion Com-pared with bipolar electrotome,the 2μm laser used in TURBT is safe and effective with few complications for treating NMIBC.