Ulinastatin improves myocardial ischemia-reperfusion injury in rats through endoplasmic reticulum stress-induced apoptosis pathway.

OBJECTIVE: To investigate the protective role of ulinastatin (UTI) on myocardial ischemia-reperfusion (I/R) injury in rats via endoplasmic reticulum stress (ERS)-induced apoptosis pathway. MATERIALS AND METHODS: A total of 60 rats were randomly divided into normal group (n=20), myocardial I/R model group (model group, n=20), and myocardial I/R model+UTI treatment group (treatment group, n=20). The myocardial function indicators [creatinine (Scr) and creatine kinase (CK)] were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to measure serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). Meanwhile, the contents of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) in rat left ventricular tissues were determined by ELISA as well. The cardiac function indexes were determined via magnetic resonance imaging (MRI) and echocardiography (ECG). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining assay was carried out to detect the apoptosis of myocardial tissues. Additionally, the expression levels of endoplasmic reticulum stress and apoptosis genes were measured through quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) assay and Western blotting analysis, respectively. RESULTS: Serum levels of alanine aminotransferase (ALT), CK, and Scr in model group were significantly higher than those in normal group (p<0.05). Besides, rats in model group had significantly lowered SOD, ejection fraction (EF, %), and fractional shortening (FS, %) than those in normal group (p<0.05). In addition, remarkably increased contents of TNF-α, IL-6, MMP-9, MDA, and ROS, as well as higher left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) were observed in model group in comparison with normal group (p<0.05). TUNEL staining results revealed that there were more apoptotic cells in model group than that in the other two groups (p<0.05). Expression levels of cysteine aspartic acid-specific protease 12 (Caspase-12) and glucose-regulated protein 78 (GRP78) were evidently higher in model group than those in normal group (p<0.05), while the expression level of B-cell lymphoma 2 (Bcl-2) was clearly lower in model group than that in normal group (p<0.05). UTI treatment partially reversed the above expression changes (p<0.05). CONCLUSIONS: UTI has a protective effect against myocardial I/R injury in rats by repressing the occurrence of ERS-induced apoptosis.

CircABCB10 promotes the proliferation and migration of lung cancer cells through down-regulating microRNA-217 expression.

OBJECTIVE: We aimed at studying the role and molecular mechanism of circular RNA circABCB10 in the progression of lung cancer (LCa). PATIENTS AND METHODS: We collected LCa tissues using quantitative real-time polymerase chain reaction (qRT-PCR) technology to determine circABCB10 expression and performed survival analysis based on the clinical data of LCa patients. At the same time, the specific effects of circABCB10 on the biological function of LCa cell lines were determined by certain cell function experiments, including cell counting kit-8 (CCK-8) test, plate cloning experiment, transwell and cell wound healing assays. The downstream key gene microRNA-217 of circABCB10 was predicted through bioinformatics analysis and the potential regulation between them was confirmed by luciferase assay. microRNA-217 was knocked down in LCa cell lines to verify its important role in the progression of LCa. RESULTS: CircABCB10 showed abnormally high expression in LCa tissues and cell lines and was related to the poor prognosis of patients. In vitro cell experiments demonstrated that knocking down circABCB10 remarkably suppressed the proliferation and migration ability of LCa cells. In addition, circABCB10 can specifically bind to microRNA-217 and negatively regulate its expression of microRNA-217 in LCa cells. Finally, cell functional experiments showed that microRNA-217 is a key downstream gene that mediates the regulation of circABCB10 on LCa cell function. CONCLUSIONS: CircABCB10, abnormally highly expressed in LCa tissues, is able to induce the malignant progression of this cancer.

[The clinical efficacy of laparoscopic cornuotomy on interstitial tubal pregnancy which diameter was shorter than 3 cm].

Objective: To investigate the clinical efficacy of Laparoscopic cornuotomy on Interstitial Tubal Pregnancy (IP) which diameter was shorter than 3 cm. Methods: The women who had IP under 3 cm diameter were selected from January, 2016 to December, 2018 at the Department of Gynecology, JiaXing Maternity and Child Health care Hospital. A total of 32 IP patients were divided into two groups. They were all treated with laparoscopic surgery. 17 patients were in study group, conducted by a cornuotomy and suturing the cornual.15 patients were in control group, conducted by a cornual resection and suturing the cornual. Patients' genenral conditions were not significantly different(all P values>0.05). The peri-surgical data and the related clinical data were compared in the two groups. Results: All the 32 patients were successfully treated by laparoscopic surgery. The mean operating time was significantly shorter for cornuotomy than for cornual resection[ (33±6) min vs (53±9) min, P<0.05].Changes in blood loss[(45±5) ml vs (50±7) ml]、the total hospital stays[ (4.4±1.4) d vs (4.6±1.4) d] and the recovery time of HCG[(16±5) d vs (15±5) d] were not significantly different between the two groups (all P values>0.05) . There were no persistent ectopic pregnancy and uterine rupture happened in two groups. Compared with the control group,the interval time to pregnancy was shorter[ (8±3) m vs (16±4) m, P<0.05] and the number of full-term pregnancy cases were more (9 vs 3, P<0.05). Conclusion: The Laparoscopic cornuotomy was feasible and safe on interstitial tubal pregnancy which diameter was shorter than 3cm. It deserved popularization in the clinical work and regarded as one of selection operative treatment on interstitial heterotopic pregnancy.

MiR-506 suppresses papillary thyroid carcinoma cell proliferation and metastasis via targeting IL17RD.

OBJECTIVE: The aim of this study was to determine the role of microRNA-506-3p (miR-506) in papillary thyroid carcinoma (PTC), and to further explore the underlying mechanism. PATIENTS AND METHODS: The expression level of miR-506 in clinical cases was detected by Real Time-fluorescence quantitative Polymerase Chain Reaction (RT-qPCR). Meanwhile, RT-qPCR was performed to determine miR-506 expression in different PTC cell lines. Bioinformatics software was used to predict the possible target genes of miR-506. Dual-Luciferase reporter gene assay together with Western blot (WB) assay were used to verify the prediction results. Finally, cellular functions such as proliferation and metastasis capacities were detected in vitro. RESULTS: RT-qPCR was used to measure the expression level of miR-506 in 80 paired PTC cases. The results showed that the expression level of miR-506 in PTC tissues was significantly decreased. In vitro, miR-506 expression was also markedly suppressed in four PTC cell lines. TPC-1 cells expressed the lowest level of miR-506. Subsequently, the target gene of miR-506 was predicted by TargetScan, miRBase and miRanda. The prediction results indicated that IL17RD was an alternative target gene of miR-506. Furthermore, miR-506 was found to remarkably inhibit the Luciferase activity of wild-type IL17RD. However, it had no effect on mutant-type. Besides, the protein expression level of IL17RD was significantly reduced in miR-506-overexpressing TPC-1 cells. More importantly, the restored expression of IL17RD could alleviate the blocking effects of miR-506 on cell proliferation, migration and invasion. CONCLUSIONS: In this study, we found that miR-506 could inhibit the proliferation and metastasis of PTC cells. Meanwhile, IL17RD might be a downstream target of the biological process. Our findings provided a new therapeutic direction for the treatment of PTC.

[Effects of endotoxin/lipopolysaccharide on early apoptosis of human neutrophil through PIM3].

Objective: To explore the effects of endotoxin/lipopolysaccharide (LPS) on early apoptosis of human neutrophil through PIM3. Methods: Venous blood samples were collected from a healthy adult volunteer to isolate neutrophils. The neutrophils were divided into control group, LPS group, and LPS+ PIM447 group according to the random number table. No treatment was given to the cells in control group. The cells in LPS group underwent LPS stimulation (1 µL, 1 µg/mL). The cells in LPS+ PIM447 group underwent PIM447 (1 µL, final amount-of-substance concentration of 5 µmol/L) intervention 30 min before having the same LPS stimulation as that in LPS group. After conventional culture for 1 h, the early cell apoptosis rate was determined with flow cytometer; the generation level of reactive oxygen species (ROS) was assessed with dihydrogenrhodamine 123 fluorescent probe staining method; and the level of PIM3 was detected by Western blotting. After conventional culture for 2 h, the cell chemotaxis distance was measured by agarose chemotaxis cell model. The sample numbers of each group in the 4 experiments were all 5. Data were processed with one-way analysis of variance and Student-Newman-Keuls test. Results: (1) The early apoptosis rate of cells in LPS group [(0.891±0.012)%] was close to that in control group [(1.351±0.183)%, P>0.05)]. The early apoptosis rate of cells in LPS+ PIM447 group [(82.057±0.121)%] was higher than that in LPS group (P<0.01). (2) The cell chemotaxis distance of cells in LPS group [(984±5) µm] was significantly shorter than that in control group [(2 241±7) µm, P<0.01]. The cell chemotaxis distance of cells in LPS+ PIM447 group [(1 785±11) µm]was significantly longer than that in LPS group (P<0.05). (3) The generation level of ROS in cells of LPS group was significantly higher than that in control group (P<0.05). The generation level of ROS in cells of LPS+ PIM447 group was significantly lower than that in LPS group (P<0.05). (4) The expression level of PIM3 in cells of LPS group (1.297±0.015) was significantly higher than that in control group (0.789±0.021, P<0.05). The expression level of PIM3 in cells of LPS+ PIM447 group (0.731±0.011) was significantly lower than that in LPS group (P<0.05). Conclusions: LPS stimulation can reduce the early apoptosis of human neutrophils. Pre-intervention with PIM447 can significantly increase the early apoptosis of neutrophils after LPS stimulation, recover the chemotaxis, and inhibit the production of ROS. The mechanism may be related to LPS promoting the expression of PIM3.

Effects of Ulinastatin on myocardial oxidative stress and inflammation in severely burned rats.

OBJECTIVE: By constructing the severe burns model in rat, we explored the effects of different doses of Ulinastatin (UTI) on protecting myocardium from oxidative stress and inflammatory reaction. MATERIALS AND METHODS: The severe burns model in rat was first constructed. Burned rats were intervened with different doses of UTI. Contents of cardiac troponin I (cTnI), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in rat serum and heart homogenate were detected by enzyme-linked immunosorbent assay (ELISA). Activities of SOD (superoxide dismutase), CAT (catalase), GSH-Px (glutathione peroxidase), and MDA (malondialdehyde) were detected by commercial kits. The inflammation and pathological changes in rat heart were observed by HE (Hematoxylin-Eosin) staining. Protein expressions of Cox-2, iNOS, NF-κB, Nrf2, and HO-1 in rat myocardium were detected by Western blot. RESULTS: Higher levels of cTnI, IL-1, IL-6, and TNF-α were found in model group than those of control group (p<0.05). Besides, decreased contents of cTnI, IL-1, IL-6, and TNF-α were observed in both UTI 50 ku/kg group and UTI 100 ku/kg group compared with those of model group (p<0.05). Decreased activities of SOD, CAT, and GSH-Px, as well as increased MDA level were observed in model group than those of control group (p<0.05). However, UTI treatment remarkably elevated SOD, CAT, and GSH-Px activities, whereas downregulated MDA level in burned rats (p<0.05). Abundant infiltration of inflammatory cells was found in the rat's myocardium of model group, which was alleviated in UTI group in a dose-dependent manner. Upregulated Cox-2, iNOS, and NF-κB, as well as downregulated Nrf2 and HO-1 were found in model group compared with those of control group (p<0.05). UTI pretreatment remarkably reversed the above-mentioned trends. CONCLUSIONS: Ulinastatin alleviates myocardial injury induced by severe burns. It exerts a protective role in myocardium via inhibiting oxidative stress and inflammatory response.

Pinopode score around the time of implantation is predictive of successful implantation following frozen embryo transfer in hormone replacement cycles.

STUDY QUESTION: Is pinopode measurement of any prognostic value? SUMMARY ANSWER: Pinopode expression was significantly associated with the occurrence of pregnancy after frozen embryo transfer. WHAT IS KNOWN ALREADY: Pinopodes are expressed in the endometrium during the implantation period. Pinopode measurement has been proposed as a marker of endometrial receptivity. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was conducted at the Center of Reproductive Medicine, Sir Run Run Shaw Hospital, between 2014 and 2016, recruiting 172 women with infertility and undergoing frozen embryo transfer following IVF treatment. Among 172 participants, 46 women took part in the first study to quantify the daily changing pattern of pinopodes 3-7 days after the initiation of progesterone therapy in the hormone replacement cycles and the remaining 126 women with infertility participated in a study to examine the relationship between pinopode count and pregnancy outcome following frozen embryo transfer in hormone replacement cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean age of participants was 29 years old. All participants received an artificial hormone replacement protocol capable of supporting successful implantation. Endometrial biopsies from 46 women were obtained 3, 4, 5, 6 and 7 days after the initiation of progesterone therapy (P + 3, n = 6; P + 4, n = 6; P + 5, n = 11; P + 6, n = 13; P + 7, n = 10, respectively). Another 126 endometrial biopsies were obtained precisely 6 days after the initiation of progesterone. Scanning electron microscopy was used to capture the pinopode images, followed by use of the image J program to quantify the count and subtype of the pinopodes. MAIN RESULTS AND THE ROLE OF CHANCE: We found that at least 60 microscopic fields were necessary to achieve a reproducible result. An intra-observer variability study showed good agreement between two measurements regarding the developing pinopode (DP) subtype (r = 0.95) and the fully developed pinopode (FDP) subtype (r = 0.86) but not for the regressing (RP) pinopode subtype (r = 0.39). The proportion of DP/total pinopodes (TP) declined rapidly form day P + 4 to a minimum on day P + 6. The percentage of FDP/TP increased rapidly from day P + 4 to reach a peak on day P + 6. On the other hand, the percentage of RP/TP reached a peak on day P + 7. Participants who conceived had a significantly (P = 0.011) higher percentage of FDP/TP on day P + 6 and significantly (P = 0.005) lower percentage of DP/TP on the same day compared with participants who did not become pregnant. Using a scoring system incorporating the percentages of DP and FDP, it was found that the pregnancy rate and the embryo implantation rate of women with a high pinopode score (82.3%; 63.0%) was significantly (P = 0.001; P = 0.046) higher than that of women with a low pinopode score (53.3%; 46.7%), respectively. There remains a possibility that the observations could have arisen due to chance. LIMITATIONS, REASONS FOR CAUTION: This study examined pinopode count and subtype in the HRT cycles, and it is uncertain whether the same observations apply to in natural cycles. WIDER IMPLICATIONS OF THE FNDINGS: Pinopodes have been questioned as a potential marker of endometrial receptivity for many years. Our results suggested that pinopode measurement may be of value in predicting pregnancy. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the grants from the general project of medicine and health in Zhejiang Province of China (2015KYA142; 2018KY106), the Key Research and Development Program of Zhejiang Province (2017C03022) and the National Natural Science Foundation of China (81701514).The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. TRIAL REGISTRATION NUMBER: ISRCTN26300668.

[Co-culture with endometrial stromal cells promotes the differentiation of menstrual blood-derived mesenchymal stem cells into endometrial epithelial cells].

Objective: To study the potential of differentiation of menstrual blood-derived mesenchymal stem cells (MenSC) into endometrial epithelial cells (EEC) in vitro. Methods: Endometrial stromal cells (ESC) and MenSC were cultured and identified by certain methods.MenSC were co-cultured with ESC, added 10 ng/ml TGF-ß1, 10 ng/ml EGF, 10 ng/ml PDGF-BB and 1×10(-7) mol/L 17-ß-estradiol.The expression of cytokeratin, which was marker of EEC, was tested by immunofluorescence in differentiated MenSC. Results: MenSC proliferated quickly in vitro, and showed fusiform shape and clear structure within 10 generations.The expression rate of superficial markers of MenSC, CD44, CD90, CD73, and CD29, were 98.4%, 90.77%, 94.75% and 97.01% respectively.The expression of vimentin, which was stromal marker, was positive in cultured ESC (P3). After co-cultured with ESC for 3 weeks, MenSC morphology changed from fibroblast-like cells into epithelial-like cells.Immunofluorescence assay showed that the differentiated MenSC expressed cytokeratin. Conclusion: Under the condition of co-culture with ESC, MenSC has the ability to differentiate into endometrial epithelial cells. Cell growth factor and estrogen play the important roles in this process.

Comparative efficacy of whole-brain radiotherapy with and without elemene liposomes in patients with multiple brain metastases from non-small-cell lung carcinoma.

PURPOSE: We explored and compared the clinical effects of whole-brain radiotherapy (wbrt) with and without elemene liposomes in patients with multiple brain metastases from non-small-cell lung carcinoma (nsclc). METHODS: We retrospectively analyzed 62 patients with multiple brain metastases from nsclc who received wbrt (30 Gy in 10 fractions) at Shengjing Hospital of China Medical University from January 2012 to May 2013. In 30 patients, elemene liposomes (400 mg) were injected intravenously via a peripherally inserted central catheter for 21 consecutive days from the first day of radiotherapy. Overall survival (os) and nervous system progression-free survival (npfs) for the two groups were compared by Kaplan-Meier analysis. Factors influencing npfs were examined by Cox regression analysis. Chi-square or Fisher exact tests were used for group comparisons. RESULTS: The median os was 9.0 months in the wbrt plus elemene group and 7.8 months in the wbrt-alone group (p = 0.581); the equivalent median npfs durations were 5.2 months and 3.7 months (p = 0.005). Patient treatment plan was an independent factor associated with npfs (p = 0.002). Tumour response and disease-control rates in the wbrt plus elemene group were 26.67% and 76.67% respectively; they were 18.75% and 62.5% in the wbrt group (p = 0.452). Compared with the patients in the wbrt-alone group, significantly fewer patients in the wbrt plus elemene group developed headaches (p = 0.04); quality of life was also significantly higher in the wbrt plus elemene group both at 1 month and at 2 months (p = 0.021 and p = 0.001 respectively). CONCLUSIONS: The addition of elemene liposomes to wbrt might prolong npfs in patients with multiple brain metastases from nsclc, while also reducing the incidence of headache and improving patient quality of life.

[Gene typing and antibiotic resistance of methicillin-resistant Staphylococcus aureus isolated from lower respiratory tract at two hospitals in Shanghai].

OBJECTIVE: To study the genotyping characteristics and antibiotic resistance of methicillin-resistant Staphylococcus aureus(MRSA) isolated from lower respiratory tract at 2 different level hospitals in Shanghai. METHODS: The subjects included 155 patients at Ruijin Hospital and Tongren Hospital between January 2013 and June 2014, including 108 males and 47 females, with a mean age of 67.8±16.5. The 155 MRSA strains were isolated from lower respiratory tract specimens and multilocus sequence typing (MLST) and spa typing were analyzed by the PCR method. The antimicrobial resistance of MRSA was tested by VITEK-32. Fisher's exact test was used for statistical analysis. RESULTS: Among the 155 strains, 28 MLST-spa molecular types were identified, of which ST764-t002(41.29%), ST239-t037(17.42%) and ST239-t030(10.32%) were the most predominant types. The MRSA strains were susceptible to linezolid, vancomycin and teicoplanin, and also had a lower resistance to trimethoprim-sulfamethoxazole and rifampin, with a susceptible rate of 83.9% and 83.2% respectively, but were highly resistant to other antibiotics. The resistance rate of ST239-t037 to trimethoprim-sulfamethoxazole was higher than that of other types, and the resistance rate of ST239-t030 to rifampin was higher than that of other types, the differences being significant(P<0.001). The mean length of hospital stay of the 155 patients was (97±84) days, and mechanical ventilation were used in 78(50.3%) patients, while 108(69.7%))patients received invasive procedures. Broad-spectrum antibiotics were used in 136 (87.1%) patients. There were differences in age, hospitalization days, smoking history, history of COPD, mechanical ventilation, and operation between the 2 hospitals(P<0.05). CONCLUSION: Most of the MRSA strains at Ruijin Hospital and Tongren Hospital between January 2013 and June 2014 were multi-drug resistant, and the susceptibility spectrum of different genotypes was different.

CASP-9 gene functional polymorphisms and cancer risk: a large-scale association study plus meta-analysis.

We investigated the association between CASP-9 polymorphisms and susceptibility to neoplasm. Fourteen studies with a total of 2733 neoplasm cases and 3352 healthy controls were included. Meta-analysis showed that the rs4645981 T allele and the rs4645981 T allele carrier were positively associated with neoplasm susceptibility [odds ratio (OR) = 1.43, 95% confidence interval (95%CI) = 1.12-1.81, P = 0.004; OR = 1.46, 95%CI = 1.10-1.93, P = 0.009, respectively]. However, the rs1052576 A allele, rs1052576 A carrier, rs2308941 T allele, and rs2308941 T carrier might decrease the risk of cancer (OR = 0.72, 95%CI = 0.58-0.89, P = 0.003; OR = 0.76, 95%CI = 0.63-0.92, P = 0.004; OR = 0.20, 95%CI = 0.09-0.45, P < 0.0001; OR = 0.21, 95%CI = 0.06-0.75, P = 0.02, respectively). There was no significant association between rs1263, rs1052571, rs2308950, rs4645978, rs4645980, rs4645982, and rs4646018 and cancer risk (all P > 0.05). In conclusion, this meta-analysis suggests that CASP-9 gene polymorphisms are involved in the pathogenesis of various cancers. The rs4645981 T allele and the rs4645981 T allele carrier might increase the risk of cancer, but the rs1052576 A allele, rs1052576 A carrier, rs2308941 T allele, and rs2308941 T carrier might be protective.

Meta-analysis demonstrates association of XRCC1 genetic polymorphism Arg399Gln with esophageal cancer risk in the Chinese population.

We made a meta-analysis of the association between X-ray cross-complementing gene 1 (XRCC1) genetic polymorphism Arg399Gln and esophageal cancer (EC) risk. Statistical analysis was performed with the Review Manager version 4.2.8 software program and STATA version 11.0. We selected 16 case-control studies for this meta-analysis, including 3591 EC cases and 5752 controls. Overall, the Gln399 allele was not associated with EC risk, compared with the Arg399 allele in the populations included in the analysis. However, stratified analysis revealed that the Gln399 allele was associated with increased EC risk among the Chinese population in a recessive model [odds ratio (OR) = 1.42; 95% confidence interval (95%CI) = 1.07-1.90; P = 0.02 for heterogeneity] and by homozygote contrast (OR = 1.43; 95%CI = 1.05-1.96; P = 0.02 for heterogeneity), particularly for the tumor histology of squamous cell carcinoma (OR = 1.46; 95%CI = 1.10-1.95 for the recessive model and OR = 1.42; 95%CI = 1.03-1.95 for the homozygote contrast). We conclude that the XRCC1 Arg399Gln polymorphism has potential as a biomarker for EC susceptibility in the Chinese population, particularly for squamous cell carcinoma.

A literature-based systematic HuGE review and meta-analysis show that CASP gene family polymorphisms are associated with risk of lung cancer.

The caspase (CASP) gene family is known to be involved in apoptosis, cytokine maturation, cell growth, and differentiation. A large number of single nucleotide polymorphisms (SNPs) in the CASP gene family have been increasingly recognized as important regulators in the development of lung cancer. However, this specific association is still controversial. In this Human Genome Epidemiology review and meta-analysis, we summarized the available evidence associating lung cancer with the CASP gene family. Seven studies, which included 1155 lung cancer cases and 1120 healthy controls, met the inclusion criteria and were included in our meta-analysis. In seven studies, 19 different SNPs have been studied in seven CASP genes, including CASP-1, -2, -5, -7, -8, -9, and -10. Meta-analysis results showed positive associations between heterozygote (A/G) of rs507879 in the CASP-5 gene, the T allele of rs12415607 in the CASP-7 gene, and the T allele and T carrier (C/T+T/T) of rs4645981 in the CASP-9 gene with lung cancer susceptibility [odds ratio (OR) = 1.83, 95% confidence interval (95%CI) = 1.07-3.12, P = 0.03; OR = 1.18, 95%CI = 1.02-1.37, P = 0.03; OR = 1.43, 95%CI = 1.12-1.81, P = 0.004; OR = 1.46, 95%CI = 1.10-1.93, P = 0.009; respectively]. However, we found that homozygote (G/G) of rs2227310 in the CASP-7 gene, del allele, heterozygote (ins/del), and del carrier (ins/del + del/del) of rs3834129 in CASP-8 could be protective factors for lung cancer (OR = 0.17, 95%CI = 0.14-0.21, P = 0.0003; OR = 0.83, 95%CI = 0.72-0.97, P = 0.02; OR = 0.74, 95%CI = 0.64-0.85, P < 0.0001; OR = 0.81, 95%CI = 0.71-0.93, P = 0.002; respectively). In conclusion, based on this meta-analysis, we suggest that SNPs in CASP-5, -7, -8, and -9 are associated with susceptibility to lung cancer.

Serum levels of selenium in patients with brain metastases from non-small cell lung cancer before and after radiotherapy.

PURPOSE: This study was to evaluate the influence of radiotherapy on the selenium serum levels of non-small cell cancer patients with brain metastases. PATIENTS AND METHODS: This prospective study included 95 non-small cell cancer patients with brain metastases treated by radiotherapy from December 2007 until November 2010. Plasma selenium levels were determined before and at the end of the radiotherapy. Age, body mass index (BMI), prior chemotherapy, pathological type and personal habits (smoking and alcoholism) were recorded for each patient. RESULTS: The mean age was 63 years; the mean BMI was 27.6. Seventy-six patients (80%) were non-smokers. Sixty-two patients (65.3%) showed no drinking habits and 8 (8.4%) have no prior chemotherapy. Thirty-nine patients (41.1%) were adenocarcinoma, 51 (53.7%) were squamous cell carcinoma and five (5.3%) were large cell carcinoma. At the beginning of radiotherapy, the mean selenium level for all patients was 90.4 µg/l and after radiation this value dropped to 56.3 µg/l. Multivariate analysis showed statistically significant difference in the plasma selenium concentration before and after radiotherapy for age (P<0.001), BMI (P<0.001), smoking (P<0.001), alcoholism (P<0.001), prior chemotherapy (P<0.001) and pathological type (P<0.001). CONCLUSION: Significant reduction in plasma levels of selenium was recorded in patients undergoing radiotherapy, suggesting attention to the nutritional status of this micronutrient and other antioxidant agents.

Safety and radiation-enhancing effect of sodium glycididazole in locoregionally advanced laryngeal cancers previously treated with platinum-containing chemotherapy regimens: A preliminary report.

PURPOSE: To determine the safety and radiation-enhancing effect of sodium glycididazole in laryngeal squamous cell carcinoma (stage T3-4,N0-3,M0) with conventional radiotherapy. PATIENTS AND METHODS: Patients with locoregional advanced laryngeal cancer (stage T3-4,N0-3,M0) were included: group 1(control, n=30)were not administered of sodium glycididazole; group 2 (test, n=30) received sodium glycididazole at a dose of 700 mg/m(2) intravenous infusion 30 minutes before radiotherapy three times a week. Surrogate end-points of efficacy were tumor and nodal size. Safety parameters were vomiting, nausea, mucositis, laryngeal edema, esophagus and skin reaction, dysphagia, dyspnea, neurological deficit. Patients were evaluated weekly during treatment for 7 weeks and thereafter monthly for 3 months. RESULTS: In the test, the overall response rate was 88.89% (95%CI, 71.00-97.00%) at 7 weeks and 92.59% (95%CI, 76.00 to 99.00%) at 1 month of follow-up. In the control, the overall response rate was 62.5% (95%CI, 41.00 to 81.00%) at 7 weeks and 58.33% (95%CI, 37.00 to 78.00%) at 1 month of follow-up. The short-term locoregional response rate was better in the test group at 7 weeks (p=0.027) and at 1 month (p=0.005) of follow-up. The test group had significantly more nausea and vomiting in weeks 1 (p=0.047), 2 (p=0.007), and 3 (p=0.01) of treatment. CONCLUSIONS: The study indicates sodium glycididazole is an effective radiation-enhancing agent that improves short-term locoregional control and is well tolerated in patients with locoregionally advanced laryngeal cancer.

Aortic root remodeling in atheromatous aneurysms: the role of selected sinus repair.

OBJECTIVE: Atheromatous ascending aortic aneurysms (AAA) frequently present with aortic regurgitation (AR) from dilatation of the sino-tubular junction (STJ) and extension of the pathological process into the root. Experience suggests that root dilatation begins in the non-coronary, then right coronary sinus. Rather than employ aortic root replacement or the David procedure, we have elected to replace the ascending aorta and remodel the STJ and involved sinuses. We studied the outcome after selective sinus replacement in 29 consecutive AAA patients between 1995 and 2001. METHODS: There were nine male and 20 females. Age ranged from 47 to 79 years (mean 67.5). Seven had arch aneurysms and four coronary artery disease. Nineteen were NYHA III or IV. Grade of AR was IV in 20, III in five and II in four. The STJ was dilated >50% of annulus diameter in each case (5.3-10.0 cm, mean 6.4 cm). All valves had three cusps. All patients underwent ascending aortic replacement. Seven had arch replacement and four coronary artery bypass. Seven had replacement of both right and non-coronary sinuses with re-implantation of the right coronary ostium. Twelve had replacement of the non-coronary sinus alone whilst nine had right coronary sinus replacement. One with dextrocardia had left coronary sinus replacement with ostial re-implantation. The graft size was within 2 mm of annulus size except for two patients (24 mm 12, 26 mm 11, and 28 mm six). Post operative echocardiographic studies were performed. None of the patients received anticoagulation. RESULTS: There were no hospital or late deaths and no thromboembolic or infective complications. Two patients had mild to moderate aortic regurgitation. These had a size 28 graft, which in retrospect was too large. Others had no significant regurgitation. CONCLUSIONS: The native aortic valve can be preserved in the majority of patients with AAA. Remodelling of the STJ and selective sinus replacement restores valve competence. Anticoagulation and prosthesis related complications are thereby avoided.

Pericardial and porcine stentless aortic valves: are they hemodynamically different?

BACKGROUND: We sought to compare the early hemodynamic performance of pericardial stentless aortic valves with that of well-established porcine stentless aortic prostheses. METHODS: A total of 169 patients (97 men and 72 women, aged 73+/-6 years) undergoing aortic valve replacement received either a pericardial (Pericarbon, Sorin Biomedica, Saluggia, Italy; n = 89) or a porcine (Freestyle, Medtronic, n = 80) stentless aortic valve. Aortic valve hemodynamics and root dynamism were assessed by Doppler echocardiography at discharge and 12 months after implantation. RESULTS: Clinical demographic data, valve size (24.0+/-1.9 vs 24.6+/-2.3 mm), and body surface area (1.85+/-0.19 vs 1.80+/-0.19 m2) did not differ between porcine and pericardial valves (both p > 0.05). The 1-year postoperative mean valve pressure gradient (4.2+/-2.6 vs 3.7+/-2.6 mm Hg), effective orifice area (2.2+/-0.8 vs 2.2+/-0.8 cm2), and left ventricular ejection fraction (62+/-13 vs 63+/-13, %) also did not differ (all p > 0.05). However, at discharge, systolic increase in aortic sinus diameter was significantly greater in pericardial valves than in porcine ones (7.7+/-5.7 vs 4.9%+/-4.2%, p < 0.01). Furthermore, pericardial valves had a greater slope of effective orifice area-systolic aortic flow relationship (0.89+/-0.07 vs 0.70+/-0.06, cm2/100 mL/s, p < 0.01). CONCLUSIONS: Nonprosthetic thin-walled pericardial valves appear to offer better aortic root dynamism and more efficient hemodynamics than those of porcine valves immediately after implant. At 1-year follow-up, however, both types of stentless valves provide equally excellent hemodynamics. The clinical choice between the two will depend on their long-term durability.

Pericardial stentless aortic valves: effects of sizing on hemodynamics and root geometry.

The objective of this study was to determine the effects of sizing policy for pericardial stentless valves on hemodynamic performance and aortic root geometry. Discharge echocardiography was performed on 103 patients out of 110 consecutive implants (54 men and 49 women, mean age 75 +/- 9 years, and 36% with Co-CABG). Valve prosthesis size was based on largest annulus size plus 1 to 2 mm in the first 50 implants (group A, n = 48). Following continuous echo assessment, sizing policy was changed to annulus size plus 3 to 4 mm in the next 60 implants (group B, n = 55). Sinotubular (ST) junction was kept within 115% of the annulus size by surgical remodeling of aortic root. In comparison with group A, group B had a 7% larger valve size (25.2 +/- 2.1 mm v 23.6 +/- 2.3, mm, P <.01) implanted for patients of same body surface area and left ventricular cavity size. However, group B has a 38% lower mean pressure gradient (4.0 +/- 2.7 v 6.5 +/- 3.2, mm Hg, P <.01), a 32% greater effective orifice area (2.3 +/- 0.9 cm(2) v 1.7 +/- 0.7 cm(2), P <.01), better root distensibility (9.3% +/- 6.0% v 6.8% +/- 4.1%, P =.026), and a lower ratio of ST junction to valve size (0.92 +/- 0.13 v 0.99 +/- 0.14, P =.009). Group B also had lower grade of prosthesis regurgitation (0.35 +/- 0.62 v 0.89 +/- 1.1, P =.002). Sizing of pericardial stentless aortic valves by annulus diameter plus 3 to 4 mm provides better valve competence and hemodynamic efficiency by improving aortic root geometry and distensibility. Pericardial stentless valves may be of advantage in elderly patients with significant geometric root mismatch.

In vivo hemodynamic characteristics of porcine stentless aortic valves.

The objective of this study was to elucidate the relationship of aortic pressure gradient (mPG) and effective orifice area (EOA) with mean systolic flow rate of left ventricle in patients who received a stentless aortic valve. Two hundred thirteen patients (age: 73 +/- 6 years, 123 men and 90 women) who received a Freestyle stentless valve in subcoronary position for aortic valve diseases were studied. EOA, mPG, and systolic aortic flow rate were determined by Doppler echocardiography at 1 and 20 months after implant. With follow-up, there was a 13% increase in EOA and a 30% decrease in mPG, both P <.01. Although systolic aortic flow did not change, the intercept of EOA-flow relationship increased significantly at late follow-up (0.56 +/- 0.13 v 0.11 +/- 0.13, P <.01). Multiple regression analysis showed that systolic aortic flow accounted for 54%, and mPG for only 27%, variation of EOA. Linear relationship between EOA and systolic aortic flow provides a comprehensive approach to describe stentless valve performance, when mean valve pressure gradient appears to be flow independent. These hemodynamic features distinguish stentless valves from stented or mechanical prosthesis. Ultimately, the variations in aortic root anatomy, surgical experience and their interactions are likely to become major determinants of in vivo performance of stentless aortic valves.