[Research progress on the relation and related mechanism of night shift work and cardiovascular disease].

Cardiovascular disease is a class of diseases involving the heart or blood vessels, which accounts for about one-third of all deaths worldwide each year. Unhealthy diet, lack of physical activity, smoking and excessive alcohol consumption are all risk factors for cardiovascular disease. With the increasing number of night shift workers, the number of patients with cardiovascular disease has increased, and night shift work has gradually become a risk factor of cardiovascular disease. At present, the mechanism of cardiovascular disease caused by night shift work is still unclear. This review summarizes the relationship between night shift work and cardiovascular disease and its related biochemical indicators, and discusses the research on related mechanisms.

[Feasibility study on the preparation of novel negative pressure materials for constructing new matrix of full-thickness skin defect wounds in rats].

Objective: To explore the feasibility on the preparation of novel negative pressure materials for constructing new matrix of full-thickness skin defect wounds in rats. Methods: The experimental research method was applied. The microstructure of polyurethane foam dressing which was commonly used in negative pressure treatment was observed under scanning electron microscope, and its pore diameter was detected (n=5). Polycaprolactone (PCL) and polybutylene succinate (PBS) were used respectively as raw materials for the preparation of PCL and PBS negative pressure materials by melt spinning technology, with the measured pore diameter of polyurethane foam dressing as the spinning spacing at the spinning rates of 15, 25, and 35 mm/s, respectively. The microstructures of the prepared negative pressure materials were observed under scanning electron microscope, and their fiber diameters were measured. The tensile strength and tensile modulus of the prepared negative pressure materials and polyurethane foam dressing were measured by tensile testing machine and composite testing machine, respectively (n=5), to screen the spinning rate for subsequent preparation of negative pressure materials. Human skin fibroblasts (Fbs) in logarithmic growth phase were co-cultured with PCL negative pressure material and PBS negative pressure material prepared at the selected spinning rate, respectively. After 1, 4, and 7 day (s) of co-culture, the cell activity and adhesion in the materials was detected by living/dead cells detection kit, and the cell proliferation level in the materials was detected by cell counting kit 8 method (n=5). A full-thickness skin defect wound was prepared on the back of 18 5-6 weeks old Sprague-Dawley rats (gender unlimited). Immediately after injury, the injured rats were divided into PCL+polyurethane group, PBS+polyurethane group, and polyurethane alone group according to the random number table (with 6 rats in each group). The wounds were covered with materials containing corresponding component and performed with continuous negative pressure suction at the negative pressure of -16.7 kPa. The wound tissue along with materials directly contacted to the wound (hereinafter referred to as wound specimens) were collected from 3 rats in each group after 7 and 14 days of negative pressure treatment (NPT), respectively. The growth of granulation tissue and the attachment of material to wound surface were observed after hematoxylin-eosin staining, the collagen fiber deposition was observed after Masson staining, and CD34 and interleukin-6 (IL-6) positive cells were detected and counted by immunohistochemical staining. Data were statistically analyzed with one-way analysis of variance, analysis of variance for factorial design, least significant difference-t test, Kruskal-Wallis H test, Mann-Whitney U test, and Bonferroni correction. Results: The microstructure of polyurethane foam dressing was loose and porous, with the pore diameter of (815±182) µm. The spinning spacing for the subsequent negative pressure material was set as 800 µm. The microstructures of PBS negative pressure material and PCL negative pressure material were regular, with vertically interconnected layers and continuous fibers in even thickness, but the fibers of PBS negative pressure material were straighter than those of PCL negative pressure material. There was no obvious difference in the microstructure of negative pressure materials prepared from the same raw material at different spinning rates. The fiber diameters of PCL negative pressure materials prepared at three spinning rates were similar (P>0.05). The fiber diameters of PBS negative pressure materials prepared at spinning rates of 25 mm/s and 35 mm/s were significantly smaller than the fiber diameter of PBS negative pressure material prepared at the spinning rate of 15 mm/s (with t values of 4.99 and 6.40, respectively, P<0.01). Both the tensile strength and tensile modulus of PCL negative pressure materials prepared at three spinning rates were similar (P>0.05). The tensile strength of PBS negative pressure materials prepared at spinning rates of 15 mm/s and 25 mm/s was significantly lower than that of PBS negative pressure materials prepared at the spinning rate of 35 mm/s (with t values of 9.20 and 8.92, respectively, P<0.01), and the tensile modulus was significantly lower than that of PBS negative pressure materials prepared at the spinning rate of 35 mm/s (with t values of 2.58 and 2.47, respectively, P<0.05). Subsequently, PCL negative pressure material was prepared at the spinning rate of 35 mm/s, and PBS negative pressure material was prepared at the spinning rate of 15 mm/s. After 1, 4, and 7 day (s) of co-culture, the number of human skin Fbs that adhered to PCL negative pressure material and PBS negative pressure material increased with time, and there was no significant difference between the two materials. After 1 and 7 day (s) of co-culture, the proliferation levels of human skin Fbs between the two negative pressure materials were similar (P>0.05). After being co-cultured for 4 days, the proliferation level of human skin Fbs in PBS negative pressure material was significantly higher than that in PCL negative pressure material (t=6.37, P<0.01). After 7 days of NPT, the materials were clearly identifiable and a small amount of collagen fibers were also observed in the wound specimens of rats in the three groups; a small amount of granulation tissue was observed in the wound specimens of rats in polyurethane alone group. After 14 days of NPT, a large number of granulation tissue and collagen fibers were observed in the wound specimens of rats in the three groups; the materials and wound tissue in the wound specimens of rats in PCL+polyurethane group could not be clearly distinguished. After 7 and 14 days of NPT, the collagen fibers in the wound specimens of rats in polyurethane alone group were denser than those in the other two groups. After 7 days of NPT, the number of CD34 positive cells in the wound specimens of rats in PBS+polyurethane group was 14.8±3.6 per 400 times visual field, which was significantly less than 27.8±9.1 in polyurethane alone group (t=3.06, P<0.05); the number of IL-6 positive cells was 60 (49, 72), which was significantly more than 44 (38, 50) in polyurethane alone group (Z=2.41, P<0.05). After 14 days of NPT, the number of IL-6 positive cells in the wound specimens of rats in PBS+polyurethane group was 19 (12, 28) per 400 times visual field, which was significantly more than 3 (1, 10) in PCL+polyurethane group and 9 (2, 13) in polyurethane alone group (with Z values of 2.61 and 2.40, respectively, P<0.05). Conclusions: The prepared PCL negative pressure material and PBS negative pressure material have good biocompatibility, and can successfully construct the new matrix of full-thickness skin defect wounds in rats. PCL negative pressure material is better than PBS negative pressure material in general.

[Research progress on the role of lncRNA in the occurrence and development of malignant mesothelioma].

Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.

[Effect of PPAR-γ agonist pioglitazone on the prolifeiration of malignant nesothelionma cells induced by HMGB1].

Objective: To investigate the effect and mechanism of PPAR-γ agonist Pioglitazone (PGZ) on the proliferation of malignant mesothelioma (MM) cells. Methods: In December 2019, MM cell lines MSTO-211H and NCI-H2452 were incubated with different final concentrations of PGZ (0, 10, 50, 100, 150, and 200 µmol/L) for different periods of time (24 h, 48 h, and 72 h) , and then the cell proliferation level was detected by CCK8 assay. After given various final concentration of PGZ (0, 10, 50, 100, 150, 200 µmol/L) the for 72 hours, the changes of number and morphology of MM cells were observed under an inverted microscope. The expressions of PPAR-γ and HMGB1 mRNA were determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) after treatment of MM cells with PGZ of 0, 10, 50, 100 µmol/L for 72 h. The MM cells were treated with PGZ at concentration of 0, 100 µmol/L for 72 h, and the protein expressions of HMGB1 were examined using Western blotting and immunofluorescence; the protein expressions of Ki67 were assessed by immunohistochemistry. Results: The cell viability rate of MM cells was decreased after treated with PGZ (P<0.05) . Cell number in PGZ-treated group was significantly less than that in control group and morphology changes were observed under light microscope. QRT-PCR results revealed significantly increased PPAR-γ mRNA expression in the PGZ-treated group compared to the control group (P<0.05) . There was a significant decrease in the mRNA expression level of HMGB1 in the PGZ-treated group (100 µmol/L) as compared to the control group in MSTO-211H (P<0.05) ; however, the expression level of HMGB1 in NCI-H2452 was an increase or no significant differences (P>0.05) . Western blotting and immunofluorescence results showed that the protein expression of HMGB1 was reduced in the PGZ-treated group compared with the control group in MSTO-211H (P<0.05) , but the protein expression of that in NCI-H2452 was no significant differences (P>0.05) . Immunohistochemistry results showed increased expression of proliferation marker Ki-67. Conclusion: Pioglitazone suppresses the proliferation of MM cells through inhibition of HMGB1 by the activation of PPAR-γ.

[The impact of CD8 and CTLA-4 expression on histopathological character and survival in mesothelioma].

Objective: To investigate the survival and death risk factors of mesothelioma cases stratified by the expression levels of CD8 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) , providing new clue to evaluate disease progression and clinical outcome. Methods: This was a retrospective case report, which included 47 clinically and pathologically confirmed mesothelioma cases on November 2016. Their clinical and pathological information, asbestos exposure history and survival data were collected. Infiltrated lymphocyte, 5-methylcytosine (5-mC) , CTLA-4, CD8 and Ki-67 antigen were detected using hematoxylin-eosin staining and immunohistochemistry. Survival time and death risk factors of mesothelioma patients with different CD8 and CTLA-4 protein expression characteristics were analyzed. And analyze the influence of Ki-67 expression on the survival of patients with different CD8 and CTLA-4 protein and gene expression characteristics. Results: Among the 47 cases, 63.8% (30/47) had low/medium level of infiltrated lymphocyte. The immunohistochemistry scores of CTLA-4, CD8, 5-mC and Ki-67 were 92.97 (54.95, 120.65) , 72.41 (36.62, 89.82) , 11.09 (3.40, 52.89) and 5.88 (2.41, 11.48) , respectively. Patients with CD8(high) CTLA-4(high) had higher 5-mC level than those with CD8(high) CTLA-4(low) (P<0.01) . The median survival time of 27 cases was 0.83±0.29 year. The median survival times of those with CD8(high) CTLA-4(high) and CD8(high) CTLA-4(low) were 0.58±0.51 year and 0.83±0.30 year, respectively (P=0.521) . The immunohistochemistry score of Ki-67 ≥5.88 was an independent death risk factor for patients with CD8(high) CTLA-4(low) (HR=8.40, P=0.01) . Under different CD8 and CTLA-4 protein expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 expression were 0.57±0.11 years and 2.31±0.46 years, respectively (P<0.01) . Under different CD8 and CTLA-4 mRNA expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 mRNA expression were 1.20±0.36 years and 3.38±0.43 years, respectively (P=0.018) . Conclusion: Mesothelioma case with high CD8 but low CTLA-4 content might coexist DNA hypomethylation. In the presence of high Ki-67 expression, their survival time appears to be shortened with increased death risk.

[Detection and comparison of fiber count concentration in processing environment of asbestos and man-made mineral fiber].

Objective: To connect with the measurement data of asbestos dust fiber concentration in foreign countries, improve the accuracy of asbestos fiber detection in China, and understand the dust exposure in the working environment of asbestos and man-made mineral fiber production and processing sites in Zhejiang Province. The fiber count concentrations of working environment in glass fiber, ceramic fiber and asbestos processing plants were measured and compared. Methods: The dust concentration in the working environment of two glass fiber factories, one ceramic fiber factory and eight asbestos products processing factories was measured. The total dust mass concentration was measured according to GBZ/T 192.1-2007, and the fiber count concentration was measured by phase contrast microscope. Kruskal Wallis was used to test and compare the dust concentration in the working environment of each post. The correlation between asbestos mass concentration and fiber count concentration was analyzed by Spearman correlation. Results: Under the phase contrast microscope, there were many short and fine asbestos fibers in the field of vision, and there were many impurities around. The average dust concentration of asbestos processing plant was 3.2 f/ml, and the dust concentration of cotton ginning was the highest (6.68 f/ml) . There was a significantly positive correlation between asbestos fiber count concentration and mass concentration (r=0.535, P=0.033) . The average fiber count concentration of glass fiber factory was 0.001 f/ml, and the highest was 0.005 f/ml. The average fiber count concentration of ceramic fiber factory was 0.001 f/ml, and the highest was 0.006 f/ml. Conclusion: The fiber count concentration in the working environment of asbestos factory in Zhejiang Province is obviously over the standard, which is one of the important reasons for the high incidence of mesothelioma in this area. Short and small asbestos fibers are easy to be ignored when counting. It is necessary to improve the actual operation process of fiber counting to form a laboratory standard in China.

[Comparison of the accuracy of neuronavigation and linear measurement in the positioning of parasagittal meningioma].

Objective: To explore the accuracy of preoperative positioning of neuronavigation and linear measurement localization in the parasagittal meningioma. Methods: Thirty-eight patients with parasagittal meningioma who underwent neurosurgery in the First Affiliated Hospital of Bengbu Medical College from January 2016 to April 2018 were preoperatively positioned with neuronavigation localization and linear measurement localization. The actual position of the tumor was observed during operation, and the accuracy of the two methods was compared. The time taken by the neural navigation positioning and the linear measurement positioning method was recorded, and the difference between the two methods was compared. Results: All cases were treated with neuronavigation and linear measurement, and the tumors were completely exposed after localization. Compared with the actual tumor center position measured during surgery, the average error distance between 38 nerve navigation and actual tumor center position was (2.7±1.9) mm, and the average error distance between linear measurement and actual tumor center position was (3.2±1.3) mm. The difference was not statistically significant, P value=0.207. Neuronavigation includes booting, data import, registration, positioning, etc., which takes an average of (22.3±2.3) minutes. The linear positioning method included image data measurement and localization, and the average time was(1.7±0.3) minutes. The difference between the two groups was statistically significant, and the P value was less than 0.001. Conclusion: The linear measurement localization method and the neuronavigation localization method have good accuracy for preoperative localization of the parasagittal meningioma.

[Application of modified brain protection double-lumen drainage tube in external drainage of chronic subdural hematoma].

Objective: To compare the clinical effects of modified double-lumen drainage tube and traditional silicone tube in external drainage of chronic subdural hematoma. Methods: Selected 49 patients suffering from chronic subdural hematoma hospitalized in the Department of Neurosurgery, the First Affiliated Hospital of Bengbu Medical College between July 2016 and June 2018 who underwent external drainage, and divided them randomly into experimental groups (using modified brain protection double lumen drainage tube in 23 cases) and control group (using traditional silicone drainage tube in 26 cases). Comparison of postoperative hematoma residual volume, the tube indwelling time, the numbers of drainage tube contact with brain tissue and arachnoid membrane, the numbers of infections, the numbers of postoperative epilepsy cases, and changes in Modified Rankin Scale scores between the two groups. Results: At the time of extubation, the residual amount of hematoma in the experimental group was (13±7) ml, and that in the control group was (17±8) ml. There was no significantly statistical difference in the residual amount of hematoma between the experimental group and the control group (P>0.05). The tube indwelling time of the experimental group was (2.0±0.9) days, and that of the control group was (2.7±0.8) days. The difference between the experimental group and the control group in the drainage tube indwelling time was statistically significant (P<0.05). No cases of drainage tube contact with brain tissue and/or arachnoid membrane appeared in the experimental group, and 7 cases of drainage tube contact with brain tissue or arachnoid membrane appeared in the control group. No infection occurred in both groups. No cases of epilepsy occurred in preoperative, and there were 0 cases of epilepsy in the experimental group and 1 case in the control group in postoperative. There were significantly statistical differences in each of the two groups in the modified Rankin scale before and after surgery (P<0.001), there was no significant difference in postoperative Modified Rankin Scale scores between the two groups. Conclusion: The modified brain protection double-lumen drainage tube has good drainage effect in the external drainage of chronic subdural hematoma, and the short tube retention time, causing fewer complications. It is a safe and effective tool for treating chronic subdural hematoma, and it is worthy of clinical promotion.

[The curative effect analysis of unilateral subfrontal combined with interhemispheric approach on the microsurgery of large anterior skull base meningioma].

Objective: To explore the surgical technique and curative effect of microsurgical resection of large anterior skull base meningioma via unilateral subfrontal and interhemispheric approach. Method: The clinical data of 14 patients with large anterior skull base meningioma who received surgical treatment in the Department of neurosurgery in First Affiliated Hospital of Bengbu Medical College from April 2015 to September 2017 were analysed retrospectively.Of 9 cases were olfactory groove meningioma and 5 cases were tuberculum sellae meningioma.The microsurgical resection approach of all the patients was the unilateral subfrontal combined with interhemispheric approach. Results: According to the Simpson classification of meningioma resection, 13 cases(92.8%) were Simpson grade Ⅰand Ⅱ, 1 case was grade Ⅲ.The clinical symptoms were improved in 12 cases (85.7%), and no improvement in 2 cases.Fourteen patients had postoperative complications in 2 cases (14.2%), and all of them were no cerebrospinal fluid leakage and death. Conclusion: Microsurgical removal of large anterior skull base meningioma through unilateral frontal and interhemispheric approach is safe and effective, providing a new way for surgical treatment of large anterior skull base meningioma. It had a positive significance for the prognosis of patients.

[Curative effect analysis of 15 cases of cervical intra-and extra-spinal tumors by microsurgical resection].

Objective: To explore the curative effect of microsurgical treatment of cervical intra- and extra-spinal tumors. Methods: The clinical data of 15 patients with cervical intra-and extra-spinal tumors in Department of Neurosurgery, the First Affiliated Hospital of Bengbu Medical College from January 2013 to February 2017 were retrospectively analyzed. According to Shaw's tumor stage: 6 cases in stage Ⅰ, 5 cases in stage Ⅱ, 3 cases in stage Ⅲ, and 1 case in stage Ⅳ. About the surgical methods: 9 cases were treated via posterior median semi-laminectomy approach, of which were internal fixation in 2 cases, and via posterior median approach spinous process and vertebral plate complex orthotopic replantation to spinal canal plasty in 3 cases, other 3 cases were operated via anterior cervical approach, including internal fixation in 1 case. After the surgery, vertebral canal MRI was adopted to evaluate the tumor, and CT three-dimensional reconstruction or X-ray of the spine was used for assessing the stability of spinal column, and Frankel grading standard was employed to evaluate the recovery of spinal cord function. Results: The tumors were totally resected in the first stage with the help of a microscope. Histological types of the tumors included schwannoma in 14 cases, gangliocytoma in 1 case. There was no leakage of cerebrospinal fluid and infection of incisional wound after operations. After the surgery, Frankel grading standard was adopted to assess the recovery of the spinal cord function, and the results showed grade D in 4 patients and grade E in 11 patients. All patients were followed-up for 1 to 24 months with an average of 13 months without tumor recurrence and spinal instability. Conclusion: Appropriate surgical approach should be selected to treat the cervical intra- and extra-spinal tumors, totally resection of the tumor could be achieved under the microscope, and the corresponding vertebral reconstruction and spinal fixation should be used to maintain spinal stability if necessary.

[Curative effect analysis of two surgical methods for removal of pituitary adenoma via endonasal transsphenoidal approach].

Objective: To compare the efficacy of endoscopic endonasal transsphenoidal surgery and microsurgery for pituitary adenomas. Methods: One hundred and ten patients with pituitary adenoma who were treated by single nostril transsphenoidal surgery in the department of neurosurgery of the First Affiliated Hospital of Bengbu Medical College from June 2014 to December 2016 were enrolled.These cases were randomly divided into endoscopic group 53 cases (including 36 cases of functional pituitary adenoma and 17 cases of non-functional pituitary adenoma) and microscope group 57 cases (including 34 cases of pituitary adenoma and 23 cases of non-functional pituitary adenomas), with no significant difference in preoperative clinical data about gender, age, tumor size and endocrine function (P>0.05). The total tumor resection rate, postoperative complication rate and the rate of functional tumor hormone levels were compared between the two groups. Results: The total resection rate of tumor in patients with endoscope and microscope group were 75.5% (40/53) and 70.2% (40/57) without statistically significant difference (P>0.05). The total resection rate and hormone level decline effective rate of functional pituitary adenomas in neuroendoscope group (91.7%, 33/36; 83.3%, 30/36) were higher than those in microscope group (70.6%, 24/34; 61.8%, 21/34) with statistically significant difference (P<0.05). Another side, there was no statistically significant difference in total resection of non-functional pituitary adenomas between endoscope group (41.2%, 7/17) and microscope group (69.6%, 16/23) (P>0.05). The total incidence of postoperative complications in endoscopic group (9.4%, 5/53) was lower than that in the microscope group (24.6%, 14/57), with statistically significant difference (P<0.05), in which the rate of postoperative complications of functional pituitary adenomas and nonfunctional pituitary adenoma in endoscopy group (8.3%, 3/36; 11.8%, 2/17) and in microscope (20.6%, 7/34; 30.4%, 7/23) had no statistical significance (P>0.05). Conclusion: Pituitary adenoma resection rate in two ways had no obvious difference, but the advantages of endoscopic surgery for functional pituitary adenomas were obvious.The incidence of postoperative complications of endoscopic surgery was lower than that of microscopic surgery, but there was no difference between functional and non-functional tumors.

[Research on the application of "H shaped" single-tube double-lumen drainage tube in the treatment of chronic subdural hematoma].

OBJECTIVE: To explore the effect of chronic subdural hematoma external drainage surgery using self-made "H shaped" flush type single-tube double-lumen drainage tube. METHODS: There were 56 cases chosen from the First Affiliated Hospital of Bengbu Medical College between Jan 2013 and Aug 2015. These patients with unilateral chronic subdural hematoma requiring surgery to place drilling external drainage catheter were randomly divided into group A (21 cases, using self-made single-tube double lumen "H shaped" drainage tube) and group B (35 cases, traditional silicone drainage tube), then the residual liquid volume after drainage on the first day, the days that the tube stay in body and the residual fluid volume after removing the tube were compared between the two groups. RESULTS: The residual liquid volume after drainage on the first day in group A was (23±15)ml, in group B was (31±15)ml. The days that the tube stay in body in group A was (2.7±1.0)d, in group B was (3.3±1.1)d, the two groups had statistical differences (P<0.05). The residual fluid volume after removing the tube in group A was (13±7) ml, in group B was (16±8)ml, but the data in these two groups had no significantly statistical differences (P>0.05). CONCLUSION: The effect of self-made "H shaped" flush type single-tube double-lumen drainage tube in the drainage of chronic subdural hematoma drainage is good, with short tube stay in the body; therefore, it is a safe and effective way to treat chronic subdural hematoma, and is worthy of clinical application.

Cytokine profile and prognostic significance of high neutrophil-lymphocyte ratio in colorectal cancer.

BACKGROUND: High circulating neutrophil-lymphocyte ratio (NLR) appears to be prognostic in metastatic colorectal cancer (mCRC). We investigated the relationship of NLR with circulating cytokines and molecular alterations. METHODS: We performed retrospective analyses on multiple cohorts of CRC patients (metastatic untreated (n=166), refractory metastatic (n=161), hepatectomy (n=198), stage 2/3 (n=274), and molecularly screened (n=342)). High NLR (ratio of absolute neutrophil-to-lymphocyte counts in peripheral blood) was defined as NLR>5. Plasma cytokines were evaluated using multiplex-bead assays. Kaplan-Meier estimates, non-parametric correlation analysis, and hierarchical cluster analyses were used. RESULTS: High NLR was associated with poor prognosis in mCRC (hazard ratio (HR) 1.73; 95% confidence interval (CI):1.03-2.89; P=0.039) independent of known prognostic factors and molecular alterations (KRAS/NRAS/BRAF/PIK3CA/CIMP). High NLR correlated with increased expression of interleukin 6 (IL-6), IL-8, IL-2Rα, hepatocyte growth factor, macrophage-colony stimulating factor, and vascular epidermal growth factor in exploratory (n=39) and validation (n=166) cohorts. Fourteen additional cytokines correlated with high NLR in the validation cohort. All 20 cytokines fell into three major clusters: inflammatory cytokines, angiogenic cytokines, and epidermal growth factor ligands. In mCRC, composite stratification based on NLR-cytokine score provided enhanced prognostic information (HR 2.09; 95% CI: 1.59-2.76; P<0.001) over and above NLR. CONCLUSIONS: High NLR is an independent poor prognostic marker in CRC and correlates with a distinct cytokine profile related to key biological processes involved in carcinogenesis. A composite NLR-cytokine stratification has enhanced prognostic value in mCRC.

Association between KRAS mutation and lung metastasis in advanced colorectal cancer.

BACKGROUND: KRAS mutations have been associated with lung metastases at diagnosis of metastatic colorectal cancer (mCRC), but the impact of this mutation on subsequent development of lung metastasis is unknown. We investigated KRAS mutation as a predictor of lung metastasis development. METHODS: We retrospectively evaluated data from patients with mCRC whose tumour was tested for KRAS mutation from 2008 to 2010. The relationships of KRAS mutational status with time-to-lung metastasis (TTLM) and overall survival (OS) were analysed. RESULTS: Of the 494 patients identified, 202 (41%) had tumours with KRAS mutation. KRAS mutations were associated with a shorter TTLM (median 15.2 vs 22.4 months; hazard ratio=1.40; P=0.002) and a two-fold greater odds of developing lung metastases during the disease course in patients with liver-limited mCRC at diagnosis (72 vs 56%, P=0.007). Overall survival did not differ by KRAS status. CONCLUSIONS: Lung metastasis was more likely to develop during the disease course in patients whose tumour had a KRAS mutation than in those whose tumour did not have a KRAS mutation. This finding may have an impact on decision making for surgical resection of metastatic disease.

Clinicopathologic characteristics and gene expression analyses of non-KRAS 12/13, RAS-mutated metastatic colorectal cancer.

BACKGROUND: KRAS mutations in codons 12 and 13 are present in ∼40% of all colorectal cancers (CRC). Activating mutations in codons 61 and 146 of KRAS and in codons 12, 13, and 61 of NRAS also occur but are less frequent. The clinicopathologic features and gene expression profiles of this latter subpopulation of RAS-mutant colorectal tumors have not yet been clearly defined but in general are treated similarly to those with KRAS 12 or 13 mutations. PATIENTS AND METHODS: Records of patients with metastatic CRC (mCRC) treated at MD Anderson Cancer Center between December 2000 and August 2012 were reviewed for RAS (KRAS or NRAS) and BRAF mutation status, clinical characteristics, and survival outcomes. To study further with an independent cohort, data from The Cancer Genome Atlas were analyzed to define a gene expression signature for patients whose tumors feature these atypical RAS mutations and explore differences with KRAS 12/13-mutated colorectal tumors. RESULTS: Among the 484 patients reviewed, KRAS 12/13, KRAS 61/146, NRAS, and BRAF mutations were detected in 47.7%, 3.0%, 4.1%, and 7.4%, respectively, of patients who were tested for each of these aberrations. Lung metastases were more common in both the KRAS 12/13-mutated and atypical RAS-mutated cohorts relative to patients with RAS/BRAF wild-type tumors. Gene expression analyses revealed similar patterns regardless of the site of RAS mutation, and in silico functional algorithms predicted that KRAS and NRAS mutations in codons 12, 13, 61, and 146 alter the protein function and drive tumorgenesis. CONCLUSIONS: Clinicopathologic characteristics, survival outcomes, functional impact, and gene expression profiling were similar between patients with KRAS 12/13 and those with NRAS or KRAS 61/146-mutated mCRC. These clinical and bioinformatic findings support the notion that colorectal tumors driven by these RAS mutations are phenotypically similar.

Preparation and characterisation of andrographolide niosomes and its anti-hepatocellular carcinoma activity.

OBJECTIVE: In this study, a novel andrographolide (AG) preparation formulation, niosomes, was prepared to improve the bioavailability and tissue distribution of AG. METHODS: The niosomal formulation of AG was prepared by film hydration/sonication method and tissue distribution was measured by liquid chromatography-mass spectrometry (LC-MS) method in mice, and anti-hepatocellular carcinoma (anti-HCC) activity was examined by MTT method in HepG2. RESULTS: Entrapment efficiency, drug-loading ratio and average particle size of AG niosomes were 72.36%, 5.90% and 206 nm, respectively. The tissue distribution in mice demonstrated that the AG niosomes were absorbed in liver much more than the free AG. Furthermore, the anti-HCC activity in HepG2 cells showed that there was no significant difference between free AG and AG niosomes. CONCLUSION: The present results suggest that AG niosomes may have a significant potential of liver targeting, which is valuable in chemotherapy of HCC.

A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy.

BACKGROUND: Whether carcinomas of the ampulla of Vater should be classified with biliary tract tumors and treated in a similar manner remains unknown. We sought to compare the outcomes of similarly staged periampullary adenocarcinomas (AAs) and analyze the chemotherapy responsiveness of AAs. PATIENTS AND METHODS: A total of 905 patients with resected periampullary adenocarcinomas were identified from a prospective surgical registry from 1988 to 2010. A second cohort of 64 metastatic AA patients from 1992 to 2009 who received either front-line fluoropyrimidine-based or gemcitabine-based chemotherapy was also identified. RESULTS: Overall survival (OS) for AAs was similar to survival with duodenal adenocarcinomas, but was significantly different from both extrahepatic biliary and pancreatic adenocarcinomas (P < 0.001 for each comparison). In multivariate analysis, AAs had a significantly improved OS in comparison with extrahepatic biliary adenocarcinomas (HR = 1.97, P = 0.006). Fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy for metastatic AAs resulted in a significant improvement in time to progression (P = 0.001) but only a trend toward benefit for OS (P = 0.07) in multivariate analysis. CONCLUSIONS: Differences in the natural history of ampullary and extrahepatic biliary adenocarcinomas exist. Analyses of metastatic ampullary adenocarcinomas suggest that fluoropyrimidine-based chemotherapy may represent a more appropriate front-line chemotherapy approach.

Astragalus membranaceus lectin (AML) induces caspase-dependent apoptosis in human leukemia cells.

OBJECTIVES: Recently, plant lectins have attracted great interest due to their various biological activities such as anti-cancer, anti-fungal and anti-viral activities. We have reported earlier concerning anti-proliferation of human cancer cell lines by a galactose-binding lectin (AML), from a Chinese herb, ASTRAGALUS MEMBRANACEUS: In the present study, detailed investigations into the mechanism of such anti-proliferation properties have been carried out. MATERIALS AND METHODS: Mechanism of apoptosis initiation in K562 cells by AML was investigated by morphology, flow cytometry and western blot analysis. RESULTS: AML induced apoptosis in a caspase-dependent manner in the chronic myeloid leukemia cell line, K562. Furthermore, we observed that cytotoxicity and apoptosis of K562 cells induced by AML were completely abolished in presence of lactose or galactose. CONCLUSIONS: Our results suggest that AML could act as a potential anti-cancer drug.

Production of xylobiose from the autohydrolysis explosion liquor of corncob using Thermotoga maritima xylanase B (XynB) immobilized on nickel-chelated Eupergit C.

In this study, a thermostable recombinant xylanase B (XynB) from Thermotoga maritima MSB8 was immobilized on nickel-chelated Eupergit C 250L. This immobilized XynB was then used to hydrolyze the autohydrolysis explosion liquor of corncob (AELC) in a packed-bed enzyme reactor for continuous production of xylooligosaccharides, especially xylobiose. When tested in batch hydrolysis of AELC, the immobilized XynB still retained its relative activity of 92.5% after 10 cycles of hydrolysis at 90 degrees C. The immobilized XynB retained 83.6% of its initial hydrolysis activity even after 168 h of hydrolysis reaction at 90 degrees C and demonstrated a half-life time of 577.6 h (24 days) for continuous hydrolysis. HPLC showed that xylobiose (49.8%) and xylose (22.6%) were the main hydrolysis products yielded during continuous hydrolysis. Xylobiose was adsorbed on an activated charcoal column and eluted with a linear gradient of 15% (v/v) ethanol to yield xylobiose with 84.7% of recovery. Also, the purity of xylobiose was up to 97.2% as determined by HPLC. Therefore, the immobilized XynB was suitable for the efficient production of xylobiose from AELC. This is the first report on the immobilization of xylanase for xylobiose production.