Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma

AIM: To explore the expression of leukemia related protein 16 (LRP16) in colorectal carcinoma, and analyze its correlation with clinicopathologic features and prognosis. METHODS: Immunohistochemistry for LRP16 was performed in 201 cases of colorectal carcinoma and 60 cases of distal normal mucosa. Medical records were reviewed and clinicopathological analysis was performed. RESULTS: LRP16 expression was detected in 117 of 201 cases of the colorectal carcinoma and in 21 cases of 60 distal normal mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa (χ 2 = 9.999, P = 0.002). LRP16 protein expression was found in 43.3% (52/120) of carcinoma at stage Ⅰ and Ⅱ , and 80.2% (65/81) of carcinoma at stage Ⅲ and Ⅳ (χ 2 =27.088, P = 0.001). Correlation between LRP16 expression and clinicopathological factors was significant in differentiation (P = 0.010), tumor size (P = 0.001), infiltrative depth (P = 0.000) and distant metastasis (P = 0.027). The difference of median survival time between cancer patients with LRP16 expression (38.0 mo) and those without was statistically significant (105.0 mo, Log rank = 41.455, P = 0.001). The multivariate survival analysis revealed that LRP16 expression was correlated significantly (Cox’s regression: P = 0.001, relative risk = 2.082) with shortened survival in the patients with colorectal cancer. CONCLUSION: The expression of LRP16 is related to the degree of differentiation, invasiveness, metastasis and prognosis of colorectal carcinoma.

EZH2 and STAT6 expression profiles are correlated with colorectal cancer stage and prognosis

AIM: To investigate the role of enhancer of zeste homologue 2 (EZH2) and STAT6 immunohistochemistry in the evaluation of clinical stages and prognosis of colorectal cancer (CRC). METHODS: The expression patterns were examined by immunohistochemistry in both tumor and adjacent non-neoplastic tissues of 119 CRC patients who underwent operation during the time period from 2002 to 2004. RESULTS: The positive rates of EZH2 and STAT6 in CRC cases were 69.7% (83 of 119) and 60.5% (72 of 119), respectively, and there was signifi cant differ-ence when compared with tumor adjacent non-neoplastic tissues (P < 0.05). In all CRC cases, patientswith EZH2-positive, or STAT6-positive expression had lower survival rates than those with EZH2-negative or STAT6-negative expression (P = 0.002 and P = 0.005, respectively). Co-expression of EZH2 and STAT6 showed signifi cantly higher levels in CRC cases of high clinical TNM stages (P = 0.001), and the expression of STAT6 was also correlated with lymph node metastasis and distant metastasis (P = 0.001 and P = 0.016, respectively). Multivariate analysis revealed that EZH2 expression was an independent prognostic indicator of CRC (P = 0.039). CONCLUSION: EZH2 and STAT6 expressions have significant values in distinguishing clinical stages of CRC and predicting the prognosis of the patients.

Magnetic resonance imaging-guided percutaneous cryoablation of hepatocellular carcinoma in special regions

BACKGROUND: Local cryoablation guided by CT or ultrasound has been widely applied in the treatment of hepatocellular carcinoma. However, it is still difficult to apply this technique in certain regions such as the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. This study aimed to evaluate the safety and efficacy of using magnetic resonance imaging (MRI)-guided percutaneous cryoablation as well as the effect of using an open MRI system in guiding and monitoring the treatment of hepatocellular carcinoma in these regions. METHODS: Cryoablation, guided by an open 0.35T MRI scanner and with the assistance of an MRI-compatible optical navigation system, was performed on 32 patients with hepatocellular carcinoma at the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. Each patient had one or two tumors. The total number of tumors treated was 36. The tumor diameters ranged from 2.5 to 10.0 cm (mean 4.7+/-1.8 cm). The cryosurgical system was MRI-compatible and equipped with cryoprobes 1.47 mm in outside diameter. Under the guidance of MRI in combination with the optical navigation system, the cryoprobes were introduced percutaneously into a tumor at the planned targeting points while critical organs or tissues were avoided. Each cryoablation procedure included two freezing-thawing cycles, and MRI images were acquired dynamically to monitor the ablation of the tumor from time to time during the operation. In order to investigate the therapeutic effects of a cryoablation procedure, AFP measurements and liver-enhanced MRI or CT-enhanced scans were performed at regular times. RESULTS: MRI and optical navigation system-guided cryoablation procedures were successfully performed on all 32 patients (36 tumor sites) and no serious complications occurred. The follow-up period ranged from 5 to 12 months. The 6- and 12-month overall survival rates were 96.8% and 90.6%, respectively. According to the diagnosis of liver-enhanced MRI scans, 10 patients (31.3%) had complete ablation, 18 (56.3%) partial ablation (>80%), 3 (9.4%) stable disease (>50% ablation), and 1 (3.1%) progressive disease (a new tumor site in the liver). The overall efficacy was 87.5%. CONCLUSIONS: MR-guided percutaneous cryoablation using optical navigation is a safe and effective minimally invasive procedure for the treatment of hepatocellular carcinoma at certain special regions, which is difficult to treat with other imaging guidance approaches. With its unique and superb imaging functions, MRI plays an important role in the display, guidance, and monitoring of the cryoablation procedure in treating hepatocellular carcinoma at these special regions. Equipped with an MRI-compatible optical navigation system, MRI-guided therapy makes the cryoablation procedure more precise and safe.

Resection of hepatic caudate lobe hemangioma:experience with 11 patients

BACKGROUND: Caudate lobectomy is now considered to be the most appropriate surgical treatment for benign tumors in the caudate lobe. But how to resect the caudate lobe safely is a major challenge to current liver surgery and requires further study. This research aimed to analyze the perioperative factors and explore the surgical technique associated with liver resection in hepatic caudate lobe hemangioma. METHODS: Eleven consecutive patients with symptomatic hepatic hemangiomas undergoing caudate lobectomy from November 1990 to August 2009 at our hospital were investigated retrospectively. All patients were followed up to the present. RESULTS: In this series, 9 were subjected to isolated caudate lobectomy and 2 to additional caudate lobectomy (in addition to left lobe and right lobe resection, respectively). The average maximum diameter of tumors was 9.65+/-4.11 cm. The average operative time was 232.73+/-72.16 minutes. Five of the 11 patients required transfusion of blood or blood products during surgery. Ascites occurred in I patient, pleural effusion in the perioperative period in 1, and multiple organ failure in 1 on the 6th day after operation as a result of massive intraoperative blood loss, who had received multiple transcatheter hepatic arterial embolization preoperatively. The alternating left-right-left approach produced the best results for caudate lobe surgery in most of our cases. All patients who recovered from the operation are living well and asymptomatic. CONCLUSIONS: For large hemangioma of the caudate lobe, surgery is only recommended for symptomatic cases. Caudate lobectomy of hepatic hemangioma can be performed safely, provided it is carried out with optimized perioperative management and innovative surgical technique.

Neurogenic nitric oxide facilitates the central nociceptive transmission of migraine attacks

Recent studies have shown that nitric oxide （NO） can induce migraine attacks at three possible sites of action： nitroxidergic nerves, the vascular endothelium, and the central nervous system. Most previous studies have focused on the former two sites of action. Several experiments using exogenic NO donors have suggested that nitroglycerin may induce migraine via central mechanisms. However, few studies have investigated the source of the NO involved in the central mechanisms of migraine. The present study used a cat model of migraine to represent migraine attacks in humans. We performed immunochemical staining of successive frozen sections of the brainstem and upper cervical spinal cord, and then used c-Fos protein expression to label nerve cell activation. We observed the effects of N^ω-nitro-L-arginine methyl ester （L-NAME）, a non-selective nitric oxide synthase （NOS） inhibitor, and 7-nitroindozole （7-NI）, a selective neuronal NOS inhibitor, on c-Fos and nNOS expression, which were induced by electrical stimulation to the dura mater near the superior sagittal sinus. The results demonstrated that c-Fos or nNOS immunoreactive cells was concentrated in the superficial layers （laminae Ⅰ and Ⅱ） of the spinal nucleus of trigeminal nerve. L-NAME and 7-NI pre-treatment significantly decreased c-Fos and neurogenic NOS expression; and there was a significant linear correlation between c-Fos and NOS expression （r = 0.858 2, P 〈 0.01）. These findings suggest that neurogenic NO could facilitate migraine nociceptive transmission to second-order neurons of the trigeminal nerve. However, L-NAME and 7-NI may block the activation of neurons in the spinal nucleus of the trigeminal nerve by inhibiting NO synthesis, and thereby attenuate acute migraine attacks.

Survival after radical cystectomy for bladder cancer:Multicenter comparison between minimally invasive and open approaches

Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer who underwent radical cystectomy(RC)in 13 centers of the Chinese Bladder Cancer Consortium(CBCC).Perioperative outcomes were compared between MIRC and ORC.The influence of surgical approaches on overall survival(OS)and cancer-specific survival(CSS)in the entire study group and subgroups classified according to pathologic stage or lymph node(LN)status was assessed with the log-rank test.Multivariable Cox proportional hazard models were used to evaluate the association among OS,CSS and risk factors of interest.Results:Of 2098 patients who underwent RC,1243 patients underwent MIRC(1087 laparoscopic RC and 156 robotic-assisted RC,respectively),while 855 patients underwent ORC.No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate.MIRC was associated with less estimated blood loss,more LN yield,higher rate of neobladder diversion,longer operative time,and longer length of hospital stay.There was no significant difference in OS and CSS according to surgical approaches(pZ0.653,and 0.816,respectively).Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement.Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS.Conclusions:Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

Comparison of unipedicular and bipedicular percutaneouskyphoplasty for treating osteoporotic vertebral compression fractures：a meta-analysis

Background Percutaneous vertebroplasty （PKP） has proved its effectiveness regarding minimal invasion, rapid pain reduction, safe cement augmentation, restoring vertebral height, and accelerating complete recovery of osteoporotic vertebral compression fractures （OVCFs）. Whether unipedicular or bipedicular PKP provides a better outcome is controversial.

Effect of resection following downstaging of unresectable hepatocelluar carcinoma by transcatheter arterial chemoembolization

Background This retrospective study was undertaken to analyze the outcome of hepatic resection in fifty-two patients with unresectable hepatocellular carcinoma （HCC） between January 2004 and December 2008.Methods Among these fifty-two patients,the mean diameter of the tumor was 7.9 cm （4.4-15.5 cm,median 8.5 cm） prior to the first transcatheter arterial chemoembolization （TACE）.After 1-6 times of TACE （median 2）,the median tumor diameter was reduced to 4.2 cm （0-8.4 cm） prior to resection.The duration between the last TACE treatment and sequential resection varied from one to six months （median 2.7 months）.Serum α-fetoprotein （AFP） levels were abnormal in thirty-eight out of the fifty-two patients.In AFP producing HCCs,AFP levels returned to normal （≤400 μg/L） in twenty-five out of thirty-eight patients.Hepatic segmentectomy,multiple hepatic segmentectomy or partial hepatic resection were performed in forty-five patients,two underwent extended left hemihepatectomy,and one underwent right posterior branch portal vein thrombectomy.One patient received a right hemihepatectomy and three had left hemihepatectomies.Results Complete tumor radiological response （CR） occurred in five patients （9.6%）.There were three cases of perioperative mortality in the fifty-two patients （5.8%）.One patient underwent salvaged orthotopic liver transplantation,and twenty-one patients observed tumor recurrence within two years.The 1-,3- and 5-year survival rates of the fifty-two patients were 77.0% （n=40）,55.0% （n=29）,and 52.0% （n=28）,respectively.The median survival time after surgery was 49 months （95% confidence interval 7.5-52.7 months）.Conclusions TACE treatment provides a better chance for HCC resection in patients initially diagnosed with unresectable HCC.Furthermore,liver resection should be performed once the tumor is downstaged to be compatible for successful resection

Predictive factors improving survival after gastric and hepatic surgical treatment in gastric cancer patients with synchronous liver metastases

Background The prognosis for patients with gastric cancer and synchronous liver metastases is very poor.However,a standard therapeutic strategy has not been well established.The clinical benefit and prognostic factors after hepatic surgical treatment for liver metastases from gastric cancer remain controversial.Methods Records of 105 patients who underwent gastrectomy regardless of hepatic surgical treatment for gastric cancer with synchronous liver-only metastases in our center between 1995 and 2010 were retrospectively reviewed.Results The overall survival rate for the 105 patients was 42.1%,17.2%,and 10.6% at 1,2,and 3 years,respectively,with a median survival time of 11 months.Multivariate survival analysis revealed that the extent of lymphadenectomy （D） （P 〈0.001）,lymph node metastases （P 〈0.001）,extent of liver metastases （H） （P=0.008）,and lymphovascular invasion （P=-0.002） were significant independent prognostic factors for survival.Among patients who underwent D2 lymphadenectomy,those who underwent hepatic surgical treatment had a significantly improved survival compared with those who underwent gastrectomy alone （median survival,24 vs.12 months; P 〈0.001）.However,hepatic surgical treatment was not a prognostic factor for patients who underwent D1 lymphadenectomy （median survival,8 vs.8 months;P=0.495）.For the 35 patients who underwent gastrectomy plus hepatic surgical treatment,D2 lymphadenectomy （P 〈0.001）,lymph node metastases （P=-0.015）,and extent of liver metastases （H1 vs.H2 and H3） （P=-0.017） were independent significant prognostic factors for survival.Conclusions D2 lymphadenectomy plus hepatic surgical treatment may provide hope for long-term survival of judiciously selected patients with hepatic metastases from gastric cancer.Patients with a low degree of lymph node metastases and H1 liver metastases would make the most appropriate candidates.However,if D2 dissection cannot be achieved,hepatic surgical treatment is not recommended.

Earlier application of loading doses of aspirin and clopidogrel decreases rate of recurrent cardiovascular ischemic events for patients undergoing percutaneous coronary intervention

Background Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention.Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation.Methods Thrombelastograph （TEG） determinations were used to evaluate the effect of antiplatelet therapy.According to the results,90 patients were divided into three groups and given different doses of aspirin and clopidogrel.Thirty patients with both an inhibition rate of aspirin 〉50% and an inhibition rate of clopidogrel 〉50% were defined as the control group.Sixty patients with an inhibition rate for aspirin 〈50% and an inhibition rate for clopidogrel 〈50% were defined as the resistance group.Patients in resistance group were randomly assigned to be given a routine dose （100 mg aspirin plus 75 mg clopidogrel per day,which we called a resistance plus routine dose group,R＋R） and a loading dose （200 mg aspirin and 150 mg clopidogrel per day,which we called resistance plus loading dose group,R＋L） of antiplatelet therapy.A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events.Results After 6 months of antiplatelet therapy,the inhibition rate of aspirin in the R＋L group increased from （31.4±3.7）% to （68.6±7.1）%,which was significantly higher than that in R＋R group,（51.9±8.2）% （P 〈0.01）.The inhibition rate of clopidogrel in the R＋L group increased from （22.1±3.8）% to （60.2±7.4）%,which was significantly higher than in the R＋R group,（45.9±4.3）% （P 〈0.01）.The occurrence rates of cardiovascular ischemic events,stent thrombosis,recurrent unstable angina and myocardial infarction in the R＋R group were 20%,36% and 17%,respectively.Occurrence was significantly increased compared with that in the control group,3%,10% and 1%,respectively （P 〈0.01）.In contrast,the occurrence rates in the R＋L group （10%,23% and 6%,respectively） were attenuated compared with those in the R＋R group （P 〈0.01 ）,although still higher than in the control group （P 〈0.01）.Conclusions Almost all of the cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention.According to the result of TEG determinations,earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events.

Nosocomial bloodstream infection in patients caused by Staphylococcus aureus： drug susceptibility, outcome, and risk factors for hospital mortality

Background Previous studies have different viewpoints about the clinical impact of methicillin resistance on mortality of hospital-acquired bloodstream infection （BSI） patients with Staphylococcus aureus （S.aureus）.The objective of this study was to investigate the mortality of hospital-acquired BSI with S.aureus in a military hospital and analyze the risk factors for the hospital mortality.Methods A retrospective cohort study was performed in patients admitted to the biggest military tertiary teaching hospital in China between January 2006 and May 2011.All included patients had clinically significant nosocomial BSI with S.aureus.Multivariate Logistic regression analysis was used to identify the risk factors for hospital mortality of patients with S.aureus BSI.Results One hundred and eighteen patients of more than one year old were identified as clinically and microbiologically confirmed nosocomial bacteraemia due to S.aureus,and 75 out of 118 patients were infected with methicillin-resistant S.aureus （MRSA）.The overall mortality of nosocomial S.aureus BSI was 28.0%.Methicillin resistance in S.aureus bacteremia was associated with significant increase in the length of hospitalization and high proportion of inappropriate empirical antibiotic treatment.After Logistic regression analysis,the severity of clinical manifestations （APACHE Ⅱ score） （odds ratio （OR） 1.22,95% confidence interval （CI） 1.12-1.34） and inadequacy of empirical antimicrobial therapy （OR 0.25,95% CI 0.09-0.69） remained as risk factors for hospital mortality.Conclusions Nosocomial S.aureus BSI was associated with high in-hospital mortality.Methicillin resistance in S.aureus has no significant impact on the outcome of patients with staphylococcal bacteremia.Proper empirical antimicrobial therapy is very important to the prognosis.

Noise-induced nitrotyrosine increase and outer hair cell death in guinea pig cochlea

Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactive nitrogen species （RNS） during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Method Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL （A-weighted） for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide （PI）, a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine （NT） in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Results Either after noise exposure or after SIN1 perfusion, outer hair cells （OHCs） death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiology of noise-induced hearing loss.

Role of microRNA-181a in the apoptosis of tubular epithelial cell induced by cisplatin

Background Cisplatin （DDP） is one of most effective and most commonly used therapeutic agent in treating tumors,it can accumulate in the kidney and lead to acute renal failure.MicroRNA-181a can induce cell apoptosis by suppressing the expression of Bcl-2 family.In the present study,we investigated the role of microRNA-181a in the apoptosis of tubular epithelial cell induced by DDP.Methods HK-2 cells were cultured,transfected with microRNA-181a inhibitor for 48 hours,and stimulated with 50 μmol/L cisplatin for 24 hours.MicroRNA-181a expression was analyzed by real time PCR,and cell apoptosis was detected by flow cytometry.Moreover,Bcl-2 and Bcl-2-associated X protein （Bax） expression were measured by Western blotting.Results MicroRNA-181a expression significantly down-regulated in cells transfected with microRNA-181a inhibitor,compared with that in untransfectd cells （21.19±2.01 vs.38.87±1.97,P 〈0.05）.Cell apoptosis induced by DDP significantly decreased in cells transfected with MicroRNA-181a inhibitor.Compared with DDP treated cells alone,Bcl-2 expression strikingly was up-regulated and Bax expression was down-regulated in cells transfected with microRNA-181a inhibitor.Conclusion One pathway of DDP induces apoptosis of tubular epithelial cell by suppressing Bcl-2 expression is achieved by regulating the target gene of MicroRNA-181a.

Characteristics of bone tunnel changes after anterior cruciate ligament reconstruction using Ligament Advanced Reinforcement System artificial ligament

Background There are different materials used for anterior cruciate ligament （ACL） reconstruction. It has been reported that both autologous grafts and allografts used in ACL reconstruction can cause bone tunnel enlargement. This study aimed to observe the characteristics of bone tunnel changes and possible causative factors following ACL reconstruction using Ligament Advanced Reinforcement System （LARS） artificial ligament. Methods Forty-three patients underwent ACL reconstruction using LARS artificial ligament and were followed up for 3 years. X-ray and CT examinations were performed at 1,3, 6, 12, 24, and 36 months after surgery, to measure the width of tibial and femoral tunnels. Knee function was evaluated according to the Lysholm scoring system. The anterior and posterior stability of the knee was measured using the KT-1000 arthrometer. Results According to the Peyrache grading method, grade 1 femoral bone tunnel enlargement was observed in three cases six months after surgery. No grade 2 or grade 3 bone tunnel enlargement was found. The bone tunnel enlargement in the three cases was close to the articular surface with an average tunnel enlargement of （2.5＋0.3） mm. Forty cases were evaluated as grade 0. The average tibial and femoral tunnel enlargements at the last follow-up were （0.8＋0.3） and （1.1＋0.3） mm, respectively. There was no statistically significant difference in bone tunnel width changes at different time points （P 〉0.05）. X-ray and CT measurements were consistent. Conclusions There was no marked bone tunnel enlargement immediately following ACL reconstruction using LARS artificial ligament. Such enlargement may, however, result from varying grafting factors involving the LARS artificial ligament or from different fixation methods.

Psychological trauma of funnel chest in adolescents and the appropriate age for minimally invasive surgery repair

Background Funnel chest has a negative effect on adolescents and it has a strong effect on adolescents＇ psychological and behavior. This study aimed to investigate the psychological characteristics and factors that affect adolescents with funnel chest and to evaluate the relationship between the patients＇ age and their physiological and psychological health. We aimed to establish an age model for maximum surgery benefits for funnel chest patients to provide an objective basis for choosing surgery. Methods The study adopted a general evaluation approach to assess the risk and benefits of minimally invasive surgery for funnel chest. The funnel chest index, the Symptom Checklist-90, and the Eysenck Personality Questionnaire were used as assessment tools to observe physiological and psychological features in funnel chest patients. A sample of 234 adolescents with funnel chest was selected from a third-grade class-A hospital in Beijing. Age groups were adopted as an independent variable, and other factors in funnel chest patients were dependent variables. Results There was a significant difference in the relapse rate for funnel chest in the different age groups （X2=11.883, P=-O.008）. There was a higher relapse rate in patients of 〈10 or 〉-19 years old than in patients of 11-18 years old. There was a significant difference in the SCL-90 total score in the different age groups （F=12.538, P=-0.0001）, the patients older than 13 years had a higher score than those younger than 13 years in the SCL-90. There was a significant difference in the standard score of E （introversion/extraversion） in the different age groups （F=10.06, P=0.0001）. There was also a significance in the funnel chest index before surgery in the different psychological scales （P〈0.01）, with a higher funnel chest index score associated with more obvious psychological trauma. Age and the number of variables, including the relapse rate, SCL-90 score, standard score of E, and standard score of N in the EPQ were significantly correlated （correlation indices were 0.402, 0.623, -0.505, and 0.473, respectively, P〈0.01）. Conclusions There are higher complication rates after surgery and relapse rates when funne{ chest patients are too young or too old. There is more obvious psychological trauma in patients with a high funnel chest index. Our results indicate that the best age for surgery for funnel chest is 14-16 years.

Evaluation of efficacy and safety of sunitinib regimen in 22 patients with metastatic renal cell carcinoma： at least 12-month follow-up

Background Sunitinib has been proved an effective new option for treatment of metastatic renal cell carcinoma （mRCC）. Analysis of clinical data of 22 patients, who were exposed to sunitinib for at least 1 year, was conducted to evaluate the long-term efficacy and safety of sunitinib for the treatment of mRCC. Methods A total of 54 patients with mRCC were treated with sunitinib malate, 50 mg/d orally, on a 4-weeks-on and 2-weeks-off dosing schedule in Peking University First Hospital. Treatment continued until disease progression, unacceptable adverse events （AEs）, or death. Among them, 22 patients continued treatment for at least I year. The clinical data of these 22 patients were prospectively collected for analysis. AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0. Tumor response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Results Median progression-free survival was 19.5 months until last follow-up. The best efficacy results achieved were complete response, partial response, and stable disease for 2, 9, and 11 patients, respectively. Objective response rate was 50%. The most common AEs were hand-foot syndrome （95%） and hypertension （91%）. Other common AEs were thyroid-stimulating hormone elevation （82%）, platelet decrease （77%）, and loss of appetite （77%）. Only one patient withdrew from treatment for cardiac infarction. Another nine patients experienced dose modifications or short-term suspensions. Conclusion Long-term exposure to sunitinib malate showed encouraging efficacy in the treatment of mRCC. At the same time, the tolerability was good.

Efficacy and safety of micafungin for invasive candida infections：a meta-analysis of randomized controlled trials

Background Invasive fungal infections such as candidiasis and mold infections cause significant morbidity and mortality in seriously ill patients.Micafungin is an echinocandin antifungal agent with potent activity against most species of Candida and Aspergillus.We did this meta-analysis to clarify whether micafungin offers superior efficacy and safety compared with other antifungal agent for treating infections associated with invasive candidiasis.Methods We did a meta-analysis of randomized controlled trials to examine whether micafungin has superior efficacy and safety compared with other antifungal agents recommended by the treatment guidelines for fungal infection.Seven trials involving 2913 patients were included in this analysis.Odds ratios （OR） and 95% confidence intervals （CI） were calculated.Results Micafungin was associated with significantly better treatment success compared with the comparator antifungal agents （modified intention to treat,2851 patients; random-effects model,OR 1.20,95% CI 1.00-1.45,P=0.0487）.In addition,micafungin was more effective than the comparators for antifungal prophylaxis of neutropenic patients undergoing hematopoietic stem cell transplantation （OR 1.47,95% CI 1.08-2.00,P=0.01）.Although there was no significant difference between the compared regimens in terms of the incidence of adverse drug effects （OR 0.94,95% CI 0.77-1.11）,fewer patients treated with micafungin withdrew from the studies because of adverse events （OR 0.64,95% CI 0.44-0.94）.Conclusions Micafungin has a good safety and tolerability profile,with an efficacy at least comparable to the other antifungal agents.Micafungin offers advantages over other agents for antifungal prophylaxis.Micafungin offers an appropriate alternative for antifungal prophylaxis rather than the treatment of invasive candida infections.

Altered regional homogeneity in spontaneous cluster headache attacks： a resting-state functional magnetic resonance imaging study

Background Functional neuroimaging study has opened an avenue for exploring the pathophysiology of cluster headache （CH）.The aim of our study was to assess the changes in brain activity in CH patients by the regional homogeneity method using resting-state functional magnetic resonance imaging technique.Methods The functional magnetic resonance imaging scans were obtained for 12 male CH patients with spontaneous right-sided headache attacks during “in attack” and “out of attack” periods and 12 age- and sex-matched normal controls.The data were analyzed to detect the altered brain activity by the regional homogeneity method using statistical parametric mapping software.Results Altered regional homogeneity was detected in the anterior cingulate cortex,the posterior cingulate cortex,the prefrontal cortex,insular cortex,and other brain regions involved in pain processing and modulation among different groups.Conclusion It is referred that these brain regions with altered regional homogeneity might be related to the pain processing and modulation of CH.

Antitumor effects of mutant endostatin are enhanced by Bcl-2 antisense oligonucleotides in UM-UC-3 bladder cancer cell line

Background Endostatin is a potent inhibitor of tumor angiogenesis. In the preliminary studies, we developed a mutant endostatin containing Arg-Gly-Asp-Arg-Gly-Asp （RGDRGD） sequences. In this study, we compared the antitumor effects of mutant endostatin and Bcl-2 antisense oligonucleotides both in combination and individually. Methods The artificially synthesized Bcl-2 ASODN （antisense oligonucleotides） included a translation-initiation site and was transfected into the bladder cancer cells by Lipofectamine. Cell growth was investigated by the tumor cell growth chart, MTT assay, caspase-3 activity detection assay, AO/EB fluorescein stain, and the annexin V-FITC apoptosis detection assay. In the in vivo study, UM-UC-3 bladder cancer cells were subcutaneously implanted into nude mice and the growth of tumor was examined. The ultrastructure of the tumor tissues in the treated and control groups were observed. Results The cell growth chart showed that the cell population of the treated combination group decreased by 52.04% compared to the control group. The inhibition rate of the treated combination group was （79.66＋6.79）%, whereas those of the individual ASODN and ES groups were （53.39＋3.22）% and （50.22＋5.46）% respectively. In the caspase-3 activity detection using AO/EB fluorescein stain and annexin V-FITC apoptosis detection assay, the co-inhibitory effect was higher than the individual inhibitory effects （P〈0.05）. There were significant differences in the inhibition of the solid tumor growth in the in vivo study. Conclusions Our findings indicated that Bcl-2 antisense oligonucleotides enhance the antitumor effects of mutant endostatin both in vitro and in vivo. We noted the synergistic effects of Bcl-2 antisense oligonucleotides combined with mutant endostatin.

Comparison of Charlson＇s weighted index of comorbidities with the chronic health score for the prediction of mortality in septic patients

Background Comorbidity is one of the most important determinants ot short-term and long-term outcomes in septic patients. Charlson＇s weighted index of comorbidities （WIC） and the chronic health score （CHS）, which is a component of the acute physiology and chronic health evaluation （APACHE） II, are two frequently-used measures of comorbidity. In this study, we assess the performance of WIC and CHS in predicting the hospital mortality of intensive care unit （ICU） patients with sepsis. Methods A total of 338 adult patients with sepsis were admitted to a multisystem ICU between October 2010 and August 2012. Clinical data were collected, including age, gender, underlying diseases, key predisposing causes, severity-of- sepsis, and hospital mortality. The APACHE II, CHS, acute physiology score （APS）, sequential organ failure assessment （SOFA） and WIC scores were assessed within the first 24 hours of admission. Univariate and multiple Logistic regression analyses were used to compare the performance of WlC and CHS. The area under the receiver operating characteristic curve （AUC） was used to predict hospital mortality over classes of risk. Results Of all the enrolled patients, 224 patients survived and 114 patients died. The surviving patients had significantly lower WlC, CHS, APACHE II, and SOFA scores than the non-surviving patients （P 〈0.05）. Combining WIC or CHS with other administrative data showed that the hospital mortality was significantly associated with age, severe sepsis, key predisposing causes such as pneumonia, a history of underlying diseases such as hypertension and congestive cardiac failure, and WlC, CHS and APS scores （P 〈0.05）. The AUC for the hospital mortality were 0.564 （95% confidence interval （CO 0.496-0.631） of CHS, 0.663 （95% CI 0.599-0.727） of WIC, 0.770 （95% CI 0.718-0.822） of APACHE II, 0.856 （95% Cl 0.815-0.897） of the CHS combined with other administrative data, and 0.857 （95% CI 0.817-0.897） of the WlC combined with other administrative data. The diagnostic value of WIC was better than that of CHS （P=0.0015）. Conclusions The WlC and CHS scores might be independent determinants for hospital mortality among ICU patients with sepsis. WlC might be an even better predictor of the mortality of septic patients with comorbidities than CHS. Chin Med J 2014;127 （14）： 2623-2627