Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer.

Metadherin (MTDH) is a multifunctional oncogene involved in tumor cell migration and metastasis through regulating a number of oncogenic signaling pathways in various human malignancies. Previous studies have demonstrated that MTDH is overexpressed in human colorectal cancer (CRC) and associated with cancer progression and a poor prognosis. However, the underlying mechanisms remain largely unknown. The present study investigated the expression and role of MTDH in CRC cells as well as the underlying mechanism of this. Western blot analysis and quantitative polymerase chain reaction were conducted to determine protein and mRNA expression of MTDH in three human CRC cell lines. A short hairpin RNA (shRNA) targeting MTDH was introduced into CRC HCT116 cells to stably inhibit MTDH expression. A Cell Counting Kit­8 assay, colony formation assay, Transwell assay and flow cytometry were used to investigate the effect of MTDH­knockdown on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was performed to examine the protein expression levels of cell growth­ and apoptosis­associated genes. The results demonstrated that MTDH was commonly expressed in CRC cell lines. MTDH silencing significantly suppressed cell growth, colony forming ability and migration while inducing the apoptosis of HCT116 cells. In addition, MTDH depletion induced S phase cell cycle arrest in HCT116 cells. Mechanistically, knockdown of MTDH markedly downregulated the expression of phosphorylated protein kinase B, c­Myc, proliferating cell nuclear antigen and B­cell lymphoma 2 (Bcl­2) protein in HCT116 cells, and the expression of p53 and Bcl­2­associated X protein was significantly increased compared with the negative control shRNA group (P<0.05), suggesting that MTDH may function through the expression of numerous types of apoptosis­associated and signaling channel proteins in CRC cells. Taken together, these data indicated that MTDH may serve as a biomarker and candidate therapeutic target for CRC.

Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in hepatocellular carcinoma cells.

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells.

[Case-control study on therapeutic effects of Rigidfix cross pins combined with Intrafix pins for the reconstruction of anterior or posterior cruciate ligament under arthroscopy].

OBJECTIVE: To evaluate therapeutic effects of Rigidfix cross pins combined with Intrafix pins for the reconstruction of anterior or posterior cruciate ligament under arthroscopy. METHODS: From January 2009 to June 2010,34 patients with anterior or posterior cruciate ligament injuries were divided into two groups : group A and group B. There were 24 patients in group A, including 19 males and 5 females,with an average age of (31.83±9.57) years old. The patients in group A were treated with anterior cruciate ligament reconstruction under arthroscopy; Rigidfix cross pins and Intrafix pins were used to fix femoral and tibial side respectively. Among the 10 patients in group B, 8 patients were male and 2 patients were female, with an average age of (27.20+7.59) years old. The patients in group B were treated with posterior cruciate ligament reconstruction under arthroscope; Intrafix pins and Rigidifix cross pins were used to fix femoral and tibial side sepectively. The drawer test and Lachaman test were used to evaluate postoperative knee stability. All the patients were followed up at least 18 months. Lysholm and Tegner knee scores were used to evaluate the clinical therapeutic effects. RESULTS: All the 34 patients were followed up, and the duration ranged from 18 to 26 months,with an average of (20.79±2.39) months. All the patients obtained good pain relief and knee stability. In group A,Lysholm scores significantly increased from 43.04±7.57 preoperatively to 85.41±4.68, 92.50±3.05, and 93.45±2.57 at 6,12, and 18 months postoperatively; Tegner scores significantly increased from 2.62±0.92 preoperatively to 7.45±1.14, 8.58±0.77, and 8.95±0.55 at 6, 12, and 18 months postoperatively. In group B,Lysholm scores significantly increased from 46.20±8.27 preoperatively to 86.40±5.14,90.40±2.67,and 92.00±3.85 at 6,12,and 18 months postoperatively ;Tegner scores significantly increased from 2.00±0.66 preoperatively to 7.10±0.99, 8.60±0.84, and 8.80±0.42 at 6,12, and 18 months postoperatively. There were no differences in Lysholm and Tegner scores between group A and B at different times during follow-up. Lysholm scores of all patients significantly increased from 43.97±7.79 preoperatively to 85.70±4.76,91.88±3.06,and 93.02±3.01 at 6,12,and 18 months postoperatively. Tegner scores of all patients significantly increased from 2.44±0.89 preoperatively to 7.35±1.09, 8.58±0.78, and 8.91±0.51 at 6,12,and 18 months postoperatively. During the follow-up period,there were no serious immunological rejection and complications. CONCLUSION: Reconstruction of anterior or posterior cruciate ligament under arthroscopy with Rigidfix cross pins and Intrafix pins fixation is feasible therapy for anterior or posterior cruciate ligament injuries, and the fixation is rigid. The therapy restores knee stability and provides a satisfactory short-term results.

[Comprehensive evaluation of AIDS spending in Dehong prefecture of Yunnan province in 2010].

OBJECTIVE: To comprehensive evaluate the rationality of Acquired Immune Deficiency Syndrome (AIDS) expenditure through the analysis of AIDS expenditure circumstances based on the application of National AIDS Spending Assessment in Dehong prefecture in 2010. METHODS: Demographic and economic indicators of Mang City, Yingjiang, Longchuan, Ruili City, Lianghe and Wanting zone in Dehong prefecture of Yunnan province were collected from the reports issued by Dehong Statistical Bureau of 2010, and HIV/AIDS epidemic indicators were collected from the annual report of national AIDS prevention and control data.NASA method was used to analyze the actual spending and demand index was used to calculate the demand of AIDS funding in these counties (cities). The correlations between HIV/AIDS expenditures and demographic, economic and HIV/AIDS epidemic index were analyzed, respectively, as well as the correlation between the expenditures of AIDS prevention and control and proportion of major transmission approaches. RESULTS: In 2010, the actual expenditures on HIV/AIDS in the 5 counties (cities) of Dehong prefecture was ¥28 752 772, the population was 1 211 400, and Gross Domestic Product (GDP) was ¥11 693. The intervention expenditures in injection drug users, sexually transmitted people, and prevention of mother to child transmission in Ruili county were ¥130 345, ¥71 484 and ¥164 100, the proportions of HIV transmission in these groups were 23.9% (49/205), 73.7% (151/205), and 0.5% (1/205), respectively; and in Lianghe county was ¥141 665, ¥257 142, and ¥99 961, and the proportions of HIV transmission were 17.1% (6/35), 80.0% (28/35) and 0.0% (0/35), respectively. The intervention expenditures in Ruili and Lianghe counties were positive related to the proportion of corresponding people with HIV infection (both r values were 0.99, all P values < 0.05). In the other 4 counties (cities) and the development zone, no correlations. The expenditures of government departments, international projects, domestic research programs and personal and family pays (r value were 0.94, 0.83, 0.99 and 0.88, respectively, all P values < 0.05) were positive related to the number.Except the personal and family pays, other sources of expenditures were all positive related to the number of reported HIV/AIDS cases (r values were 0.94, 0.89 and 0.81, respectively, all P values < 0.05). CONCLUSION: Population and HIV/AIDS epidemic index were considered as factors in AIDS spending. The expenditures corresponded with the demand of different areas basically.

[The application of National AIDS spending assessment in a county of Dehong prefecture, Yunnan province, China].

OBJECTIVE: To calculate the actual expenditures in a county of Dehong prefecture, Yunnan province, China by using the method of National AIDS Spending Assessment (NASA) in 2010. METHODS: Data were collected through NASA data collection form based on adapted NASA classification in the county of Dehong prefecture from October to December, 2011, and complemented by semi-structured interview with 16 well trained programmatic and financial representatives in 8 spending units. Data were entered in Resource Tracking Software (RTS) V 2009.3.0, and SPSS 13.0 was used for data processing and analysis. RESULTS: The NASA estimations showed that the county spent a total of ¥16 235 954 on HIV/AIDS in 2010. Public funds constituted 96.3% of the total expenditure (¥15 630 937), followed by Global Fund which accounted for 3.0% (¥484 585) and private sources which accounted for 0.7% (¥120 432). Findings based on NASA categories showed that AIDS spendings were mainly on 4 areas, and expenditure on Care & Treatment was ¥12 401 382 (76.4% of total expenditure), followed by Prevention which accounted for 14.3% (¥2 325 707), Program Management & Administration which accounted for 7.8% (¥1 268 523) and human resources which accounted for 1.5% (¥240 342). The most beneficial population group was People Living with HIV (PLHIV), accounting for 84.7% of total expenditure. (¥13 753 428), followed by 4.8% for high risk population, including female sex workers and their partners (¥297 333), injection drug users and their partners (¥293 143), men having sex with men and their partners (¥185 136) and 1.5% (¥241 429) for the general population. CONCLUSION: The local funds for HIV/AIDS in this county was insufficient. The local government should increase corresponding funds based on central government funding. Care and treatment was the first spending priority in the county and the investment of prevention services needs to be increased. Prevention and treatment and care should be combined to ensure the effectiveness of comprehensive prevention and treatment of AIDS.

[Initial experience of 640-slice CT coronary angiography in pacemaker patients].

OBJECTIVE: To investigate the feasibility and image quality of coronary artery angiography with 640-slice CT system in the pacemaker patients. METHODS: ECG-triggered 640-slice CT coronary angiography was performed in 16 pacemaker patients. Image quality of the fifteen coronary segments and metal-related artifact originating from pacemaker were assessed by two experienced radiologists in consensus. Image quality was assessed using a 4-point grading scale. ECG trigger information was recorded. RESULTS: The rate of available diagnostic images was 99.07% (Grade 1 in 83.64%, Grade 2 in 15.42%, Grade 3 in 0.47% and Grade 4 in 0.47% of patients, respectively). Image quality and the effect of streak artifact were similar between the high heart rate group and low heart rate group (P > 0.05) and between normal pacing group and arrhythmia group (P > 0.05). In coronary MSCT angiography, streak artifact of the pacemaker can render segments of the coronary artery uninterpretable, especially on S1, S2, S3, S4 and S8 segments of the coronary artery. Small shifts in the reconstruction window resulted in significance reduction of streak artifact (χ(2) = 151.818, P < 0.01). CONCLUSIONS: 640-slice gated CT coronary angiography could provide excellent image quality for patients with pacemaker. The streak artifact induced by pacemaker on some segments of the coronary artery could be improved by small shifts in the reconstruction window.

[Cost-effectiveness of female sex worker interventions by using SEX 2.0 Tool in Dehong prefecture, Yunnan province].

OBJECTIVE: To perform cost-effectiveness analysis of interventions in female sex workers in Dehong prefecture in China, with an aim of providing evidence for rational resource allocation in female sex worker interventions in the future. METHODS: The data of expenses for female sex worker interventions in Dehong from 2005 - 2007 were obtained through questionnaire survey. Meanwhile, the data from baseline survey in 2004, from surveillance of female sex workers from 2005 through 2007 as well as from the special survey on sexual transmission in 2007 were collected. Intervention effectiveness was estimated by using SEX 2.0 Tool recommended by UNAIDS. The cost-effectiveness ratio is calculated as the total cost divided by the number of estimated non-HIV patients due to these interventions. RESULTS: The total cost for female sex worker interventions is 916 400 RMB from 2005 through 2007, and a total of 3297 female sex workers were effectively intervened in these three years. Thus, the actual intervention cost for each female sex worker (unit cost) is 277.9 RMB. If all the intervention work is performed as required, the predicted unit cost for female sex worker intervention would be 500.5 RMB. During the period of 2005 through 2007, 69 female sex workers had been successfully prevented from HIV infection; therefore, the cost-effectiveness ratio is 13 282 RMB. CONCLUSION: Intervention among female sex workers is highly cost-effective.

[Value of Radiation Therapy Oncology Group guidelines based on MR imaging in diagnosing lymph node metastasis of nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: Radiation Therapy Oncology Group (RTOG) and other major cooperative groups endorse the consensus guidelines for the delineation of the node levels in stage N0 cases. But it is unclear if these guidelines can be extrapolated to N+ cases. This study was to explore the value of RTOG guidelines in delineating cervical target volumes for nasopharyngeal carcinoma (NPC) patients with lymph node metastasis. METHODS: Conventional magnetic resonance imaging (MRI) of the nasopharynx, including plain and contrast enhanced sequences, was performed on 254 naive NPC patients. The lymph nodes were divided into six cervical levels plus retropharyngeal nodes (RN) according to RTOG guidelines proposed in 2003. RESULTS: Anatomic boundaries of node levels were observed clearly on MRI. Of the 254 patients, 107 (42.1%) had obvious lymph node necrosis, 78 (30.7%) had extracapsular nodal spread, four (1.6%) had skipped metastasis. The levels of lymph node metastases in 51 (20.1%) patients were beyond RTOG guidelines, 42 of which were above cranial level IIb, six were behind the anterior edge of the trapezius muscle, and 23 were below the caudal of level IV; 20 patients had two regions of lymph node metastases beyond RTOG guidelines. No patient only with lymph node metastasis beyond RTOG guidelines was found. CONCLUSIONS: MRI is feasible to diagnose cervical node metastasis with RTOG guidelines. The boundaries of node levels should be enlarged rationally when delineating target volumes for the N+ NPC patients according to RTOG guidelines.

[Analysis of the epidemiologic patterns of HIV transmission in Dehong prefecture, Yunnan province].

OBJECTIVE: To uncover the transmission patterns of the HIV epidemic in Dehong prefecture. METHODS: The reviewed case reports, data of sentinel surveillance, testing and special survey were analyzed by SAS 8.0 program. The transmission patterns were modeled by utilizing data including sizes of the whole population and the high risk groups, high risk behavior data from 1989 to 2007, and the population index such as sex ratio and fertility rate. RESULTS: In 2005, case reports showed the proportion of people infected with HIV through sexual contact was 39.1%, and 46.9% in 2006. Among 1636 cases reported between January 1 to September 20, 2007, the proportion of people infected with HIV through sexual contact was 52%. From 1989 to 2007, the proportion of HIV infection among drug users was declining, while HIV infection through sexual contact was rising after standardizing the population tested/surveyed. The Asian Epidemic Model has shown that the proportions of incident HIV infections through sexual transmissions were 50.6%, 52.3% and 52.7% respectively from 2005 to 2007. Correspondingly, the proportions of incident cases by injecting drug user were 48.9%, 47.2% and 46.7% respectively during this period. Moreover, the Workbook method has shown that, among adults living with HIV in 2007, 50.3% were infected through injecting drugs and 48.4% through unsafe sexual activity. CONCLUSION: The rapid rise in HIV infections through injecting drug in Dehong prefecture has been initially curbed. HIV epidemic has already witnessed a change from predominantly through drug injecting-related activity to an almost equally fuelled epidemic by sexual and drug-related transmission.

[Study of prophylactic intra-iliac and hepatic arterial infusion chemotherapy against pelvic recurrence and liver metastasis after radical resection for rectal cancer].

OBJECTIVE: To study the effects of prophylactic intra-iliac and hepatic arterial infusion chemotherapy on pelvic recurrence and liver metastasis after radical resection for rectal cancer. METHODS: Eighty-four rectal cancer patients,undergone radical resection on Dukes stage B or C,were randomly assigned to postoperative intra-iliac and hepatic arterial infusion chemotherapy group(group I) and routine vein chemotherapy group(group II). Five-year survival and recurrence rates were compared between the two groups. RESULTS: Among the 84 rectal cancer patients with radical resection, the 5-year liver metastasis and pelvic recurrence rates were 30.2% (13/43) and 18.6% (8/43) respectively in group II, 17.1% (7/41) and 9.8% (4/41) in group I, the difference was significant between 2 groups (chi(2)=4.31, P<0.05). The mean tumor-free survival time was 26.2 months in group I and 15.8 months in group II (t=5.05, P<0.01), the difference was significant (t=5.05, P<0.01). The five-year survival rate in group I (65.9%) was significantly higher than that in group II (56.5%) (u=8.86, P<0.01). Cox multivariate analysis showed that, compared with those in group II, the relative risks of pelvic recurrence and liver metastasis in group I decreased 20% (coefficient of relative risk: 0.7959), and the five-year mortality also decreased 20% (coefficient of relative risk: 0.8034). CONCLUSION: Prophylactic intra-iliac and hepatic arterial infusion chemotherapy can reduce the rates of pelvic recurrence and liver metastasis after radical resection of rectal cancer.