Association between smoking and Behçet's disease: a nationwide population-based study in Korea.

BACKGROUND: There have been conflicting results about the association between Behçet's disease and smoking. Smoking has been reported to be a protective factor for Behçet's disease, whereas smoking may have a role in triggering Behçet's disease. OBJECTIVES: The aim of this study was to investigate the incidence of Behçet's disease in Korea according to smoking status using nationwide population data. METHODS: We analysed clinical data from individuals 20 years of age and older who received a health examination arranged by the Korean national insurance programme between 2009 and 2012. The incidence of Behçet's disease was analysed according to smoking status reported by individuals during their health examination. Newly diagnosed cases of Behçet's disease were identified using claims data from baseline to the date of diagnosis or until 31 December 2016. RESULTS: The risk of Behçet's disease was lower in current smokers compared with never-smokers regardless of the amount and duration of smoking. The decreased risk of Behçet's disease in current smoker persisted after adjusting for age, sex, regular exercise, drinking status, BMI, diabetes mellitus, hypertension, and dyslipidaemia, history of stroke and/or history of ischaemic heart diseases. LIMITATIONS: Genetic susceptibility or family history of Behçet's disease was not considered. CONCLUSIONS: This study found a decreased incidence of Behçet's disease in current smokers compared with never-smokers. Further investigation of the pathophysiology responsible for the negative association between smoking and Behçet's disease is needed.

DNA Repair: Translation to the Clinic.

It has been well established that an accumulation of mutations in DNA, whether caused by external sources (e.g. ultraviolet light, radioactivity) or internal sources (e.g. metabolic by-products, such as reactive oxygen species), has the potential to cause a cell to undergo carcinogenesis and increase the risk for the development of cancer. Therefore, it is critically important for a cell to have the capacity to properly respond to and repair DNA damage as it occurs. The DNA damage response (DDR) describes a collection of DNA repair pathways that aid in the protection of genomic integrity by detecting myriad types of DNA damage and initiating the correct DNA repair pathway. In many instances, a deficiency in the DDR, whether inherited or spontaneously assumed, can increase the risk of carcinogenesis and ultimately tumorigenesis through the accumulation of mutations that fail to be properly repaired. Interestingly, although disruption of the DDR can lead to the initial genomic instability that can ultimately cause carcinogenesis, the DDR has also proven to be an invaluable target for anticancer drugs and therapies. Making matters more complicated, the DDR is also involved in the resistance to first-line cancer therapy. In this review, we will consider therapies already in use in the clinic and ongoing research into other avenues of treatment that target DNA repair pathways in cancer.

[Application of surgical cricothyrotomy in emergency and complicated airway management].

Objective:To explore the feasibility of intercricothyrotomy in emergency airway management. Method:Characteristics of 27 cases underwent surgical cricothyrotomy were analyzed. Result:The main causes of emergency were severe trauma of head and neck, larynx stenosis, interspaces infection of the floor of the mouth and submaxillary space, etc; all the patients were divided into 2 groups : surgical cricothyrotomy as the first choice (group A,16/27) and surgical cricothyrotomy after conventional tracheotomy (group B,11/27); The average time of opening airway for group A was much shorter than group B ï¼»(58.12±24.41)s, (739.09±245.29)s,respectively, P<0.01)ï¼½; Bleeding in group A (14 cases) was much less than group B (13 cases) ï¼»(2.36±1.16)ml, (4.65±4.31)ml,respectively, P<0.01ï¼½; Except 1 cases died from primary disease, 4 cases with laryngeal stenosis underwent laryngeal dilation with T type expansion tube and 2 cases of bilateral recurrent laryngeal nerve palsy, the average time with tracheal tube of the remaining 20 patients was (12.35±7.29)d, no postoperative complications such as larynx or tracheal stenosis were found. All of them were successfully extubation. Conclusion:Surgical cricothyrotomy procedure is fast and safe with simple and convenient that can be used as the preferred method of rapid airway opening when a critical respiratory tract was difficult to manage.

Twist2 and CD24 expression alters renal microenvironment in obesity associated kidney cancer.

OBJECTIVE: Obesity emerged as a major public health problem worldwide, and prolonged condition with increased BMI causes various metabolic disorders include the development of kidney cancer. The metabolic changes alter the renal microenvironment and thereby promoting tumor. Hence, detailed studies of genes that regulate these this changes are keen to understand. MATERIALS AND METHODS: Initially, we successfully initiate kidney tumor using prolonged intake of a high-fat diet in Wistar rats, which are confirmed with pathological changes observed through histological sectioning. The expression of Twist2 and CD24 was assessed using Immunohistology and Western Blotting in a different time interval of kidney cancer. RESULTS: The rats fed with high-fat diet for 8 months shows 1.5 times increased in body mass whereas rats fed with high-fat diet for 16 months shows triple the size when compared with controls. Histological sectioning confirms the development of lesions and proteinaceous casts in 8 months high-fat fed rats, whereas we observed the high proliferative mass of cells in 16 months high-fat fed rats. Interestingly, we also observed elevated expression of Twist2 in initial stages of kidney cancer, which are down-regulated in the latter stages of kidney cancer. The experiments with CD24 shows the gradual increase of the expression of CD24 as a tumor develops to the next level. CONCLUSIONS: The correlation between Twist2 and CD24 expression conclude that Twist2 overexpression in initial stage augments CD24 to express more in the latter stage of kidney cancer. Reversely, the overexpression of CD24 and down-regulation of Twist2 in later stages of kidney cancer suggest the CD24 expression is dependent on Twist2 expression level.

Supraglottic jet oxygenation and ventilation during colonoscopy under monitored anesthesia care: a controlled randomized clinical trial.

OBJECTIVE: Supraglottic jet oxygenation and ventilation may provide active pulse oxygenation and ventilation in patients with respiratory suppression. This randomized controlled clinical study was designed to determine the efficacy and safety of supraglottic jet oxygenation/ventilation during monitored anesthesia care (MAC) by intravenous (IV) infusion of propofol in patients undergoing colonoscopy. PATIENTS AND METHODS: Forty-nine adult patients receiving colonoscopy were randomly divided into two groups: the control group with passive oxygen supply from regular nasal cannula (N = 24) and the supraglottic jet oxygenation/ventilation (SJV) group with active pulse oxygen supply and ventilation using a manual jet ventilator (N = 25). MAC was induced and maintained by intravenous injection of propofol. HR, ECG, BP, SaO2 were continuously monitored during and 1 hour after the procedure. RESULTS: Demographic characteristics were similar in height, weight, age and BMI (Body Mass Index) between the two groups. Compared to the control group, the SJV group had similar averaged lowest SaO2, but highest SaO2 in SJV group were significantly lower during operation (p = 0.01). The proportion of maximum chest rise movement were increased significantly in SJV group (p = 0.03) compared with control group. Demographic characteristics were similar in the times needed to use facial mask ventilation, percentage of time to maintain SaO2 above 96%, average PetCO2 during the procedure, or complications between the two groups. CONCLUSIONS: SJV can provide adequate oxygenation/ventilation during monitored anesthesia care and convenient monitoring for patients' breath, without complications.

Low CHD5 expression activates the DNA damage response and predicts poor outcome in patients undergoing adjuvant therapy for resected pancreatic cancer.

The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.

A PC-based laparoscopic surgery skills training and assessment system.

The purpose of this study is to build a cost-effective and easy-to-popularize laparoscopic training system based on improving traditional training box. The system has the capability of objective skills assessment and the function of automatic recording of training process and results, as well as 3-dimensional coordinate tracking of instruments. The results of pilot experiment in laparoscopic-assisted grip skill assessment had been shown the system can assess the different grip ability level between the senior surgeons and junior residents. Regarding to the evaluation of training effectiveness, five subjects without laparoscopic surgery experiences were asked to perform grip training for five days to observe their training curves. According to the experimental results, the total time taken for subject 1 to subject 5 are improved by 54.9%, 52.0%, 60.6%, 23.3%, and 63.5% separately.

Waldenström macroglobulinaemia presenting as a perirenal mass: a case report.

Perirenal masses are a rare manifestation of Waldenström macroglobulinaemia (WM). We report a 70-year-old male diagnosed with Waldenström macroglobulinaemia arising as a huge perirenal mass, which was discovered by abdominal ultrasound and computed tomography. The patient underwent ultrasound-guided aspiration biopsy and the histopathological examination showed a monoclonal lymphoplasmocitoid proliferation of B-cells arranged in a diffuse pattern. This case report shows not only the importance of image and biopsy studies, but also the good response to chemotherapy with the CHOP regimen.

Synthetic radiation-inducible promoters mediated HSV-TK/GCV gene therapy in the treatment of oral squamous cell carcinoma.

OBJECTIVE: To investigate the therapeutic effect of herpes simplex virus thymidine kinase (HSV-TK) gene mediated by synthetic radiation-inducible promoters in the treatment of oral squamous cell carcinoma (OSCC) in vitro and in vivo. METHODS: The plasmids pcDNA3.1(+)E6-HSV-TK were constructed, in which the HSV-TK genes were mediated by synthetic radiation-inducible promoters. The recombined plasmids were transfected into the Tca8113 cells and golden hamster buccal carcinoma, respectively. Low-dose radiotherapy was used to upregulate the HSV-TK genes expression. HSV-TK mRNA was assayed by RT-PCR. Apoptosis and proliferating cell nuclear antigen were detected respectively by in situ end-labeling and immunohistochemical method. RESULTS: Compared with control group, the comparative survival rate of Tca8113 cells in HSV-TK/GCV/IR group was markedly decreased and the golden hamster buccal carcinoma in HSV-TK/GCV/IR group was obviously suppressed. Up-regulation of HSV-TK gene expression was found in the Tca8113 cells and in the golden hamster buccal carcinoma resulting from exposure to low-dose irradiation. The apoptosis indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly higher than those without irradiation. At the same time, the proliferation indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly lower than those without irradiation. CONCLUSION: The results indicate that the synthetic radiation-inducible promoters can serve as a molecular switch to adjust the expression of HSV-TK gene in the treatment of OSCC, and low-dose induction radiation can significantly improve therapeutic efficiency.

Remote metastatic cervical carcinoma to kidneys mimicking bilateral renal abscesses.

A 53-year-old woman presented bilateral renal masses, which were interpreted as abscesses with a computed tomography scan 9 years after primary surgery for cervical carcinoma. Subsequent biopsies under ultrasound guidance revealed metastatic adenocarcinoma of kidneys originating from the cervical carcinoma. Clinical detection of renal involvement from cervical cancer is extremely rare. There were only seven cases reported in the literature, and three cases were interpreted as abscesses initially. In comparison with these cases, the time between renal metastases and initial detection of cervical carcinoma is the longest in our case.

Investigation of the corticotropin-releasing hormone-proopiomelanocortin axis in various skin tumours.

BACKGROUND: Various types of external stress cause the skin and central neuroendocrine system to express corticotropin-releasing hormone (CRH)-proopiomelanocortin (POMC) axis-related hormones. However, the precise role of the CRH-POMC axis-related hormones in various skin tumours is unclear. OBJECTIVES: This study examined expression patterns of the CRH-POMC axis-related hormones in skin tumours. METHODS: The production of CRH, adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various tumour cell lines including HaCaT and primary keratinocytes was examined using an enzyme-linked immunosorbent assay. Immunohistochemical analysis of the skin tumours was also performed. RESULTS: CRH, ACTH and alpha-MSH were strongly expressed in malignant skin tumour cell lines such as G-361 and DX-3 (both malignant melanoma, MM). However, normal and haematological malignancy cell lines did not express the CRH-POMC axis-related hormones. Immunohistochemical analysis of the skin tumours showed that MM (80%), squamous cell carcinoma (SCC, 70%) and basal cell carcinoma (BCC, 10%) had strong immunoreactivity (++/+++) for CRH. Strong ACTH and alpha-MSH expression was observed in MM (70% and 50%, respectively), SCC (80% and 60%, respectively) and BCC (70% and 50%, respectively). CONCLUSIONS: We report that an increase in the level of the CRH-POMC axis-related hormones is associated with malignant skin tumours such as MM. These results highlight the importance of the CRH-POMC axis-related hormones in the malignant tendency of skin tumours.

Redistribution of androgen receptors in acquired hormone-refractory prostate cancer cells.

The dynamic translocation of androgen receptors (ARs) in prostate cancer cells after hormone conversion was studied. The prostate cancer cell line LNCaP was converted into androgen-independent sublines after long-term treatment with 5alpha-reductase inhibitor and steroid-depleted medium. Immunohistochemical, immunofluorescent staining and laser scanning microscopy were used to observe the redistribution and serial translocation of ARs in these tumor cells. The androgen-independent tumor cells (LNCaP/Fin and LNCaP/HR) grew slower than native cells with fibroblastic-like characteristics. On immunohistochemical and immunofluorescent double staining, translocation and exocytosis of ARs were noted in androgen- independent tumor cells much more markedly than in native cells. Furthermore, laser-scanning microscopy revealed serial image changes of AR vesicle shifting and exocytosis in androgen-converted tumor cells. Translocation and exocytosis processes were observed in androgen-independent prostate cancer cells. ARs lose partly normal cellular biologic role during hormone manipulation.

Increasing expression of GST-pi MIF, and ID1 genes in chemoresistant prostate cancer cells.

The differential expression of genes and related proteins of multidrug resistance in chemoresistant prostate cancer cell lines were elucidated in this study. RNA extracted from doxorubicin-resistant rat prostate cancer (PCa) cells (AT3/ADR1000) and native PCa cells was hybridized to expression arrays containing cDNAs from 588 known genes. Differential expression of selected genes was confirmed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. Protein contents were measured by fluorescent flow cytometry and immunoblotting. Localization of selected proteins in cells was observed by immunocytochemical staining. Up-regulation of eleven genes and down-regulation of one single gene were displayed in the chemoresistant prostate cancer cells. Overexpression of mRNAs in macrophage migration inhibitory factor (MIF), DNA binding protein inhibitor 1 (ID1), and glutathione S-transferase-pi (GST-pi) were confirmed by gene-specific RT-PCR. Protein over-expression of GST-pi, MIF, and ID1 in resistant cells were 3.3-, 1.5-, and 1.5-fold to native cells, respectively. Immunocytochemistry revealed that GST-pi, MIF, and ID1 were present primarily in the cytoplasm of tumor cells, but ID1 also could be found in the nucleus. AT3/ADR1000 drug-resistant PCa cells displayed significantly increased expression of GST-pi, MIF, and ID1 proteins when compared with native PCa cells. It indicates these genes may play a role in drug resistance of prostate cancer.

Modulation of MDR-1 gene by MIF and GSTpi with drug resistance generation in hormone independent prostate cancer.

The expression of MIF and GSTpi were upregulated in prostate cancer cells with mulitdrug resistant phenotype. The aim of this study is to determine the relationship between these genes and multidrug resistance (mdr-1) gene in acquired multidrug resistance of prostate cancer. The expression of MIF, GSTpi and gp-170 in multidrug resistant (MDR) subline or native cells were determined using flow cytometry and western blotting. The mRNA level of various genes was analyzed with RT-PCR method. The chemosensitivity of tumor cells and stable transfectants to paclitaxel was measured using MTT (tetrazolium bromide) assay. The protein levels of MIF, GSTpi and gp-170 increased in MDR sublines of prostate cancer when compared with their parental cells. The MIF and GSTpi stable transfectants expressed higher MIF and GSTpi protein levels than their parental cells in western blotting analysis, respectively. The expression of mdr-1 gene and the production of pg-170 were also increased in either MIF or GSTpi stable transfectants when compared with vector control by using RT-PCR and flow cytometric analysis. The MTT results demonstrated that the increased chemoresistance was correlated with the increased production of gp-170 protein in either MIF or GSTpi transfectants. The upregulation of MIF and GSTpi during the development of acquired drug resistance of hormone independent prostate cancer may simultaneously and partially modulate the activation of gp-170.