BACKGROUNDTo study the effect and safety of tissue specific gene therapy of suicide gene for lung adenocarcinoma.

METHODSRetroviral vector of G1CEACDNa contained a carcinoembryonic antigen (CEA) promoter regulated cytosine deaminase expression cassete (CEA/CD). By means of infection of virus, tissue specific expressing vectors and non-specific expressing vectors were transfected into A549 cell, which was CEA-producing lung adenocarcinoma cell line and then xenografted in nude mice, and the anti-tumor effect was evaluated. Then the retrovirus was injected directly into the tumor mass on nude mice, and the sensitivity of the xenograft to G1CEACDNa/5-fluorocytosine (5-FC) and the side effects were observed.

RESULTS(1) After transfected and untransfected A549 cells were implanted into nude mice, there was no difference in tumor formation among all the groups. (2) After 5-FC administration, the tumor transfected with tissue-specific gene displayed a higher sensitivity to the drug than those treated with non-specific in vitro gene-therapy. (3) The tumor-bearing nude mice were randomized in a blind manner based on comparable size to receive the supernatant of recombinant retrovirus G1CEACDNa followed by 5-FC, and significant growth suppression could be observed. (4) Comparing to the group with injection of 5-fluorouracil (5-FU) alone, tissue-specific suicide gene therapy showed lower suppression to bone marrow.

CONCLUSIONSThe results suggest that tissue-specific suicide gene therapy may play an important role in individual treatment of lung cancer.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

Vasectomy damage is a common complication of open nonmesh hernia repair. This study was a retrospective analysis of the characteristics and possible causes of vas deferens injuries in patients exhibiting unilateral or bilateral vasal obstruction caused by open nonmesh inguinal herniorrhaphy. The site of the obstructed vas deferens was intraoperatively confirmed. Data, surgical methods, and patient outcomes were examined. The Anderson-Darling test was applied to test for Gaussian distribution of data. Fisher's exact test or Mann-Whitney U test and unpaired t-test were used for statistical analyses. The mean age at operation was 7.23 (standard deviation [s.d.]: 2.09) years and the mean obstructive interval was 17.72 (s.d.: 2.73) years. Crossed (n = 1) and inguinal ( n = 42) vasovasostomies were performed. The overall patency rate was 85.3% (29/34). Among the 43 enrolled patients (mean age: 24.95 [s.d.: 2.20] years), 73 sides of their inguinal regions were explored. The disconnected end of the vas deferens was found in the internal ring on 54 sides (74.0%), was found in the inguinal canal on 16 sides (21.9%), and was found in the pelvic cavity on 3 sides (4.1%). Location of the vas deferens injury did not significantly differ according to age at the time of hernia surgery ( ≥ 12 years or <12 years) or obstructive interval (≥15 years or <15 years). These results underscore that high ligation of the hernial sac warrants extra caution by surgeons during open nonmesh inguinal herniorrhaphy.
Male ; Humans ; Young Adult ; Adult ; Child ; Vas Deferens/surgery* ; Herniorrhaphy/methods* ; Retrospective Studies ; Hernia, Inguinal/surgery* ; Iatrogenic Disease ; Laparoscopy

OBJECTIVETo evaluate the safety and efficacy of individual cylindrical abdominoperineal resection (CAPR) for locally advanced low rectal cancer.

METHODSFrom June 2011 to February 2012, 11 patients with locally advanced low rectal cancer underwent individual CAPR. There were 7 male and 4 female patients, aged from 32 to 74 years with a median of 64 years. Forty-seven patients underwent classic CAPR from January 2008 to February 2012. Preoperative and postoperative parameters such as clinical information of patients, tissue morphometry and complications were compared.

RESULTSIn the individual surgical group, 6 patients were treated with one side levator ani muscle totally or partially reserved, 3 patients with sacrococcyx reserved, and 2 patients with dissection close to the anterior rectal wall. Compared with classical surgery, the individual surgical specimens of horizontal section area ((2197 ± 501) mm(2)) and intrinsic muscle layer outer area ((1722 ± 414) mm(2)) were small, but the difference was not statistically significant (P = 0.150 and 0.167). The operative time, intraoperative blood loss, circumferential resection margin, total cross sectional tissue area, cross sectional tissue area outside the muscularis propria and bowel perforation rate between the two groups were not significantly different. Individual CAPR showed less incidence of chronic perineal pain (2/11, χ(2) = 6.116, P = 0.013) and sexual dysfunction (2/9, χ(2) = 4.412, P = 0.036) compared with classic CAPR.

CONCLUSIONSIndividual CAPR has the potential to reduce the risk of chronic perineal pain and sexual dysfunction without influencing the radical effect when compare with classic CAPR for the treatment of low rectal cancer.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Perineum ; surgery ; Postoperative Complications ; epidemiology ; Rectal Neoplasms ; pathology ; surgery ; Rectum ; surgery ; Survival Rate ; Treatment Outcome

OBJECTIVETo study surgical treatment of postoperative stricture of anastomosis for lower rectal cancer.

METHODSThe data of 9 cases who were diagnosed as postoperative stricture of anastomosis after operation of intersphincteric resection for lower rectal cancer during January 2008 to June 2011 were analyzed retrospectively. Transanal excision of stricture were used in 3 cases diagnosed as membranous stricture. Transanal radial incision of stricture were used in 5 cases diagnosed as tubulous stricture. Biologic patch was used to repair the defect of the posterior wall of rectum after excision of severe stricture in 1 case.

RESULTSAll 9 cases of postoperative stricture of anastomosis were cured by surgery. Anal dilation were performed every day by patients themselves after discharge. Digital examination showed that 1 to 2 fingers could pass through the anastomosis after operation. The patient whose rectal defect was repaired by biological patch underwent colonoscopy examination two weeks after operation. Colonoscopy showed that the biological patch had been filled with granulation and integrated into the surrounding intestinal tissue. All patients defecated without difficulty and the anal function of all patients was good after restoration of intestinal continuity.

CONCLUSIONAggressive surgery, combining with the use of biological patch if necessary is an effective therapy of postoperative stricture of anastomosis for lower rectal cancer.

Aged ; Anastomosis, Surgical ; Constriction, Pathologic ; surgery ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications ; surgery ; Rectal Neoplasms ; surgery ; Rectum ; surgery ; Retrospective Studies

OBJECTIVETo investigate the antitumor effect of lycorine on renal cell carcinoma ACHN cells and explore the possible mechanism.

METHODSWe used flow cytometry to examine the effect of lycorine on ACHN cell cycle and apoptosis. The cell proliferation, migration and invasion were assessed with MTS assay, wound healing assay, and Transwell assay, respectively. Colony forming assay was performed, and the mRNA and protein levels of Bax, Bcl-2, survivin, caspase-3, cyclin D1 and CDK4 were measured with qRT-PCR and Western blotting.

RESULTSLycorine obviously inhibited the proliferation of ACHN cells with an IC(50) of 24.34 µmol/L. Lycorine also induced apoptosis of ACHN cells, caused cell cycle arrest at G(0)/G(1) phase, and suppressed the colony forming ability of the cells in a dose-dependent manner. The migration and invasion of ACHN cells were significantly inhibited by 5 µmol/L lycorine. Lycorine up-regulated the mRNA levels of CDK4, Bax, caspase-3 while down-regulated the levels of survivin, Bcl-2 and Cyclin D1; the protein levels of CDK4 and Bax were increased and cyclin D1, Bcl-2 and surviving expressions were decreased, but caspase-3 expression showed no significant changes following the treatment.

CONCLUSIONLycorine has obvious antitumor effect against ACHN cells, suggesting its value as a new therapeutic agent for renal cell carcinoma.

Amaryllidaceae Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Carcinoma, Renal Cell ; pathology ; Caspase 3 ; metabolism ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Phenanthridines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the major cause of in-stent restenosis (ISR). Intervention proliferation and migration of VSMCs is an important strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase inhibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of G0/G1 phase cells after 12 h (69.57±3.65 vs. 92.50±1.68, P=0.000), 24 h (80.87±2.24 vs. 90.25±0.79, P=0.000) and 48 h (88.08±3.86 vs. 88.87±2.43, P=0.427) as compared with control group. Roscovitine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concentration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine (30 μmol/L) led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.
Animals ; Cell Cycle ; drug effects ; Cell Line ; Cell Movement ; drug effects ; Graft Occlusion, Vascular ; drug therapy ; metabolism ; pathology ; Muscle, Smooth, Vascular ; metabolism ; pathology ; Myocytes, Smooth Muscle ; metabolism ; pathology ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Rats

OBJECTIVETo explore the effects of Yishen Zhuanggu decoction ([Chinese characters: see text], YSZGD) on the fracture healing and function of wrist joint in osteoporotic distal radius fractures (ODRF) of elderly patients.

METHODSNinety patients of ODRF were treated with splint external fixation and YSZGD, including 28 males and 62 females, with an average age of 63 years (ranged, 61 to 91 years). According to AO classification, all the patients were classified as type A or B1. Among the patients, 80 patients had a type of Colles fracture,7 patients were with a type of Smith fracture,and 3 patients had a type of Barton fracture. They were randomly divided into three groups included TCM, Western medicine and control group (30 cases each group) after the fractures were fixed manually by splint. Patients in TCM group took YSZGD orally, one potion and two time each day; the patients in Western medicine group treated with Calcitonin (50 units, intramuscular, 2 times each week), Caltrate D (1 tablets, taken orally, one time each day) and Alfacalcidol Soft Capsules (0.5 units, taken orally, one time each day); and the patients in control group took no medicine. X-ray examination on the fractured wrist was taken at the 4, 6, 8, 12th weeks after treating to observe, the fracture healings, the evaluation of wrist function and comparision of curative effects were taken at the 2nd month.

RESULTSThe fracture healing time in TCM group was 7.12 +/- 2.32 weeks and that in the Western medicine group was 9.25 +/- 3.05 weeks, showing significant differences between them (PC < 0.05), and that in the control group was 11.57 +/- 1.93 weeks which was longer thant in that in the two medicine groups (P < 0.05); According to Dienst wrist rating system, the excellent and good rates of three groups were 93.3%, 86.7% and 60% respectively which showing significant differences between medicine groups and control group (P < 0.05), and the curative effects of medicine groups were more excellent than that of control group through Ridit analysis.

CONCLUSIONYSZGD can promote the fracture healing evidently and shorten the healing time, whose curative effect surpassed Western medicine and promoted the restoration of wrist function.

Aged ; Aged, 80 and over ; Bone Density Conservation Agents ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fracture Fixation ; Humans ; Male ; Radius ; surgery ; Radius Fractures ; drug therapy ; surgery ; Treatment Outcome

BACKGROUNDEndoplasmic reticulum (ER) stress and ER stress-mediated apoptosis were reported to be involved in the pathogenesis of several diseases. In a recent study, it was reported that the ER stress pathway was activated in the lungs of lipopolysaccharide (LPS)-treated mice. It was also found that the C/EBP homologous protein (CHOP), an apoptosis-related molecule, played a key role in LPS-induced lung damage. The aim of this study was to verify whether LPS could activate the ER stress response in airway epithelial cells and which molecule was involved in the pathway. This study was also aimed at finding new reagents to protect the airway epithelial cells during LPS injury.

METHODSER stress markers were observed in LPS-incubated NCI-H292 cells. SiRNA-MUC5AC was transfected into NCI-H292 cells. The effects of dexamethasone and erythromycin were observed in LPS-induced NCI-H292 cells.

RESULTSLPS incubation increased the expression of ER stress markers at the protein and mRNA levels. The knockout of MUC5AC in cells attenuated the increase in ER stress markers after incubation with LPS. Dexamethasone and erythromycin decreased caspase-3 activity in LPS-induced NCI-H292 cells.

CONCLUSIONSLPS may activate ER stress through the overexpression of MUC5AC. Dexamethasone may protect human airway epithelial cells against ER stress-related apoptosis by attenuating the overload of MUC5AC.

Animals ; Apoptosis ; drug effects ; genetics ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Dexamethasone ; pharmacology ; Endoplasmic Reticulum ; drug effects ; metabolism ; Erythromycin ; pharmacology ; Humans ; Lipopolysaccharides ; pharmacology ; Mice ; Mucin 5AC ; genetics ; metabolism ; RNA, Small Interfering

BACKGROUNDAlthough bronchoscopy has been widely performed in China, little has been known about its current state and development. In order to investigate the clinical application of bronchoscopy and make instructions for future education and development, the Chinese Society of Respiratory Diseases conducted postal surveys in both 2008 and 2010 in China.

METHODQuestionnaires were sent to 40 tertiary grade A hospitals in 2008 and 58 tertiary grade A hospitals in 2010 to investigate bronchoscopies performed in 2007 and 2009 respectively.

RESULTSThirty (75%) hospitals returned the completed questionnaires in 2008 and forty-one (71%) hospitals in 2010. All the respondents possessed flexible bronchoscopes. Fifty percent of the respondents had less than five in 2007, while more than 50% of the respondents had 5-9 bronchoscopes in 2009. All the respondents performed a radiograph or CT scan before bronchoscopy. Percentage of general anesthesia and no pre-medication before bronchoscopy increased, while atropine usage decreased in 2009 compared to 2007. During bronchoscopy, pulse oximetry was the most widely used monitoring method. Most respondents used the nasal route to perform routine bronchoscopy. After the procedure, they used sinks to wash and glutaraldehyde to disinfect the bronchoscopes. The total number of flexible bronchoscopies performed during 2007 was 37 874 and the average was 1262. Whereas in 2009, the total number was 60 178 and the average was 1468. Diagnostic bronchoscopy was more widely used than therapeutic bronchoscopy. The mortality rate was 0.076‰ in 2007 and 0.032‰ in 2009.

CONCLUSIONSThe two surveys, to some extent, reflected the current status and development of bronchoscopy in China. The results are worthy of future education and developing of new guidelines. Regular surveys and monitoring of bronchoscopies across China are needed.

Bronchoscopy ; methods ; utilization ; China ; Hospitals ; statistics & numerical data ; Humans ; Surveys and Questionnaires