Experimental and Theoretical Study of Gamma Radiolysis and Dose Rate Effect of o-Cresol Formaldehyde Epoxy Composites.

Gamma radiolysis behaviors and mechanisms of silica-filled o-cresol formaldehyde epoxy are studied at 2.20 × 10-5 to 1.95 × 10-1 Gy/s. The radiolysis-induced changes in chemical structures do not severely affect its thermostability. The slightly deteriorated mechanical strength at temperature exceeding 100 °C is accompanied by the declining glass transition temperature (from 185.9 to 172.2 °C) and enhanced damping ability. The gas yields of hydrogen, methane, and carbon dioxide manifest a remarkable dose rate effect. Based on the Schwarzschild law, their yields at an extremely low dose rate are accurately predicted by the established master curves. Besides, the latent radiolysis of gas products and postradiation effect are found with caution. The radiation-caused residual spin species are proved to be composed of silica defects and a phenoxy-type free radical with a tert-butyl group, according to the experimental results, theoretical calculations, and spectra simulations. The lower vertical ionization potential (7.6 eV) and adiabatic ionization potential (7.1 eV) are primarily due to the ionization of the benzene ring moiety with the tert-butyl group, which is likely to suffer from radiolysis. The calculated bond dissociation energy (260.8-563.5 kJ/mol) of the typical chemical bonds of epoxy is consistent with its radiolytic vulnerability and degradation mechanisms.

[Effects of ZnO nanoparticles on proliferation and apoptosis of human lung epithelial BEAS-2B cells].

OBJECTIVE: To investigate the effects of ZnO nanoparticles (ZnO NPs) on proliferation and apoptosis of human lung epithelial cells BEAS-2B and its molecular mechanisms. METHODS: BEAS-2B cells were treated with ZnO NPs at concentrations of 3, 6 and 12 µg/ml for 12 h and 24 h, the control group was not treated with ZnO NPs, each with 3 replicate wells. Cell viability was detected by CCK-8 method, and the half lethal concentration (IC50) was analyzed. Then, the BEAS-2B cells were treated with ZnO NPs at selected concentrations of 3 and 6 µg/ml for 24 h respectively,each group was set with 3 replicate. Cell morphology was observed under inverted microscope. The morphology of cell nuclei was observed by Hochest33342 staining. The morphology of apoptosis was observed by AO staining and scanning electron microscopy. Cell cycle progression, cell apoptosis rate and the level of reactive oxygen species(ROS)were detected by flow cytometry. Western blot was used to detect the expression levels of Bcl-2 and Bax protein. RESULTS: Compared with the control group, the cell viability of cells treated with ZnO NPs were decreased significantly(P＜0.01), and the IC50 was 6.13 µg/ml at 24 h of drug treatment. After the cells were treated with ZnO NPs for 24 h, the levels of ROS were increased significantly(P＜0.05, P＜0.01)in 3 µg/ml, 6 µg/ml groups. The cell cycle was arrested at G2/M phase, chromatin condensation and apoptotic bodies were induced, apoptosis rate was increased significantly(P＜0.01) in 6 µg/ml group. The expression of Bcl-2 was decreased(P＜0.05), and the expression of Bax was increased (P＜0.05) in cells treated with 6 µg/ml ZnO NPs for 24 h. CONCLUSION: ZnO NPs induced ROS accumulation, blocked progress of cell cycle and induced cell apoptosis in BEAS-2B cells.

[Clinical observation of pre-suture ligation and suture knot positioning in single-operator circumcision with the stapler for children].

OBJECTIVE: To observe the clinical effects of pre-suture ligation and suture knot positioning in single-operator circumcision with the stapler. METHODS: Totally 120 six to fourteen years old children with phimosis or redundant prepuce were equally and randomly assigned to receive traditional single-operator circumcision with the stapler (group 1), single-operator circumcision with double suture knots for positioning the cutting plane with the stapler (group 2), or pre-suture ligation plus single-operator suture knot positioning circumcision with the stapler (group 3). We recorded and comparatively analyzed the operation time, intraoperative blood loss and hematoma, the number of residual suture knots, the patients' satisfaction with foreskin reservation, sutured frenulum and incision aesthetics, and the rates of surgical conversion, severe postoperative dysuria, severe wound exudation and perioperative anxiety of the parents and surgeon. RESULTS: Statistically significant differences were observed among the three groups in the operation time, intraoperative blood loss, incidence of intraoperative hematoma, number of residual suture knots, the patients' satisfaction with foreskin reservation, sutured frenulum and incision aesthetics, and the rates of surgical conversion, severe postoperative dysuria, severe wound exudation and perioperative anxiety of the parents and surgeon (P < 0.05). Compared with group 1, group 3 showed obviously less operation time and intraoperative blood loss and lower incidence of intraoperative hematoma, number of residual suture knots and rates of surgical conversion and perioperative anxiety of the parents and surgeons, and higher rates of patients' satisfaction with foreskin reservation, sutured frenulum and incision aesthetics. The intraoperative blood loss, incidence of intraoperative hematoma, and the rates of severe postoperative dysuria, severe wound exudation and perioperative anxiety of the parents and surgeon were lower in group 3 than in group 2. CONCLUSION: Pre-suture ligation plus single-operator suture knot positioning circumcision with the stapler helps reduce the operation time, intraoperative blood loss, incidence of intraoperative hematoma, number of residual suture knots and rates of surgical conversion and perioperative anxiety of the parents and surgeon, and increase the patients' satisfaction with foreskin reservation, sutured frenulum and incision aesthetics.

[Single- versus double-suture knot for positioning the cutting plane in circumcision with a stapler].

OBJECTIVE: To observe the clinical effect of single-suture versus that of double-suture knot in positioning the cutting plane in circumcision with a stapler. METHODS: We randomly assigned 120 patients with redundant prepuce or phimosis into three groups of an equal number to receive traditional circumcision without suture knot (group 1), circumcision with single-suture knot (group 2), and circumcision with double-suture knot (group 3) for positioning of the cutting plane. We recorded and compared the operation time, intraoperative blood loss, the rates of frenulum sewing, non-frenulum sewing, poor frenulum sewing and surgical conversion, intraoperative anxiety of the doctors, postoperative ecchymosis, and satisfaction with the retained ventral and dorsal prepuce and postoperative penile appearance among the three groups. RESULTS: There were statistically significant differences among the three groups in the surgery time, intraoperative blood loss, the rates of frenulum sewing, non-frenulum sewing, poor frenulum sewing and surgical conversion, intraoperative anxiety of the doctors, and satisfaction with the retained ventral and dorsal prepuce and postoperative penile appearance, (P < 0.05), but not in postoperative ecchymosis (P = 0.849). The rate of satisfaction with the retained dorsal prepuce was remarkably higher in group 3 than in group 2 (P = 0.003), and the intraoperative anxiety rate of the doctors was lower in the former than in the latter group (P = 0.003). CONCLUSIONS: Both single- and double-suture knots for positioning the cutting plane in circumcision with a stapler can help reduce the operation time, intraoperative blood loss, the rates of frenulum sewing, non-frenulum sewing, poor frenulum sewing and surgical conversion, intraoperative anxiety of the doctors, and satisfaction with the retained ventral and dorsal prepuce and postoperative penile appearance, and double-suture knot positioning has an even higher application value in decreasing the intraoperative anxiety of the doctors and increasing the satisfaction with the retained dorsal prepuce.

[Modified urethral reconstruction with lingual mucosa for complicated anterior urethral stricture].

OBJECTIVE: To investigate the efficiency and complications of modified urethral reconstruction with lingual mucosa in the treatment of complicated anterior urethral stricture (CAUS). METHODS: We retrospectively studied the clinical data on 10 cases of CAUS treated by modified urethral reconstruction with lingual mucosa from December 2017 to June 2019 concerning the age of the patients and the causes, location and length of urethral stricture. We statistically analyzed the pre- and post-operative maximum urine flow rate (Qmax), scores on Mental Status Scale in Non-psychiatric Settings (MSSNS) and quality of life (QOL) scores and observed post-operative complications such as abnormal taste, tongue numbness, urinary tract infection, urethral diverticulum, and urethral stricture. RESULTS: Compared with the baseline, Qmax was significantly improved and the MSSNS and QOL scores dramatically decreased at 3, 6 and 12 months after surgery (P < 0.01). Paraurethral infection developed in 1 case postoperatively, which was cured after dressing change, external urethral orifice stenosis occurred in another, which was improved after regular urethral orifice expansion, and mild tongue numbness was found in 2 cases at 1 month but gradually restored to abnormal. Urethrography showed no urethral diverticulum before catheter removal. CONCLUSIONS: Lingual mucosa is an ideal alternative material for urethral reconstruction in the treatment of CAUS, and lateral lingual mucosa can be easily obtained. Modified urethral reconstruction by embedding lingual mucosa in the dorsal base of the urethra, with the advantages of definite effectiveness and few postoperative complications, is worthy of clinical application.

[Prostatic artery embolization for high-risk patients with benign prostatic hyperplasia: A clinical effect observation].

OBJECTIVE: To observe the clinical effect of prostatic artery embolization (PAE) in the treatment of high-risk patients with BPH. METHODS: Nine high-risk patients with BPH underwent PAE in the Third Affiliated Hospital of Anhui Medical University from January 2016 to June 2018. We followed up the patients and obtained their IPSS, quality of life score (QOL), postvoid residual urine volume (PVR), maximum urinary flow rate (Qmax), prostate volume (PV), hours of undisturbed sleep (HUS), Self-Rating Anxiety Scale score (SAS) and incidence of postoperative complications before and at 6, 12 and 24 months or longer after surgery, followed by comparative analysis of the parameters. RESULTS: Compared with baseline, IPSS, QOL, PVR, Qmax, PV, HUS and SAS were all significantly improved in the patients at 6, 12 and ≥24 months after PAE (P < 0.05). Only 1 case complained of mild numbness in the buttocks, which was gradually relieved after acupuncture therapy. CONCLUSIONS: Prostatic artery embolization is definitely effective for the treatment of high-risk patients with BPH with the bladder volume ≥200 ml, with few postoperative complications, and can be used as an effective therapeutic supplementary for improving the urination symptoms of the patients.

Gamma Radiation Chemistry of Polydimethylsiloxane Foam in Radiation-Thermal Environments: Experiments and Simulations.

The γ radiolysis behavior of polydimethylsiloxane (PDMS) in the radiation-thermal environments (dose rate, 0.2 Gy/s) is studied to pinpoint the basic knowledge of the temperature (20-70 °C) effects. The non-monotonous temperature effects on the formation of gas products, paramagnetic species in silica, and cross-linking density are proposed to correlate with the complex chemical reaction mechanisms. Besides, molecular dynamics simulation and theoretical calculation are first performed simultaneously based on the radical chemistry and intricate material composition, making it easier to comprehend and further harness the radiolysis mechanisms and structure deterioration of PDMS. The γ radiation-induced primary gas products and dominant cross-linking phenomena are reproduced by the molecular dynamics simulations with a reactive force field, and the reaction mechanisms and physicochemical interactions among PDMS chains, gas products, reactive radicals, and silica fillers are thoroughly studied at the atomic scale. The thermochemistry of the barrierless radical coupling reactions and reactions with explicit high-barrier transition states is calculated at the M06-2X theoretical level with the 6-311g(d, p) basis set. The barrierless reactions are all exothermal with the heat release of 321-618 kJ/mol, while the potential barriers for reactions with explicit transition states vary between 37 and 229 kJ/mol. The results show that γ radiation-induced radicals are crucial for the ensuing gas formation and cross-linking reactions, especially for the radical coupling reactions. The radical chemistry involved in the radiolytic PDMS is the key to understand and simulate its radiolysis behavior, according to the experimental and simulated results.

Heparin-binding protein measurement improves the prediction of myocardial injury-related cardiogenic shock.

BACKGROUND: Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcomes in patients with postoperative myocardial injury-related cardiogenic shock (MIRCS). We aimed to evaluate and validate HBP as a prognostic biomarker for postoperative MIRCS. METHODS: We performed a case-control study in 792 patients undergoing cardiac surgery from January 1, 2016, to August 1, 2019, including 172 patients with postoperative MIRCS and 620 age- and sex-matched controls. The association between HBP and MIRCS was determined by multivariate logistic regression analysis. Receiver operating characteristic curves (ROCs) with area under the curve (AUC) were performed to calculate the cut-off value, sensitivity and specificity. The association between HBP and cardiac troponin T (cTnT) was determined by multivariable linear regression analysis. Blood samples were drawn from the coronary sinus and arterial line of the cardiopulmonary bypass (CPB) before aortic cross-clamping (time point 1) and 5 min after aortic declamping (time point 2). RESULTS: Before aortic cross-clamping, coronary sinus HBP (HBPCS1) showed no differences between the two groups. However, after declamping, the MIRCS group had a significantly higher sinus HBP level (HBPCS2) than did the control group. HBPCS2 predicted MIRCS with an AUC of 0.85 (95% CI: 0.81-0.89, cut-off: 220 ng/ml, sensitivity: 92% and specificity: 70%). After adjusting for confounding factors, we found that HBP was an independent risk factor for MIRCS (OR: 7.65, 95% CI: 4.86-12.06, P < 0.01) and was positively associated with cTnT (ß > 0, P < 0.01). CONCLUSIONS: Elevated levels of coronary sinus HBP were useful biomarkers for predicting MIRCS after cardiac surgery.

Dehydrocostus lactone inhibits in vitro gastrinoma cancer cell growth through apoptosis induction, sub-G1 cell cycle arrest, DNA damage and loss of mitochondrial membrane potential.

INTRODUCTION: The purpose of the present study was to evaluate the antiproliferative activity of dehydrocostus lactone against human BON-1 cancer cell lines and to explore the possible underlying mechanism. MATERIAL AND METHODS: MTT cell viability assay was used to determine cytotoxic effects of dehydrocostus lactone in BON-1 cells. Fluorescence and transmission electron microscopic (TEM) techniques were used to study the effect of the compound on cellular morphology and apoptosis. Flow cytometry was used to assess the effect on cell cycle phase distribution. Effects of the drug on cell apoptosis and mitochondrial membrane potential were analyzed by flow cytometry using annexin v and rhodamine-123 as fluorescent probes. RESULTS: The results of the present study indicated that dehydrocostus lactone significantly (p < 0.01) inhibited the growth of BON-1 cancer cells. These growth inhibitory effects of dehydrocostus lactone on BON-1 were found to be time and concentration-dependent. The IC50 of dehydrocostus lactone were found to be 71.9 µM and 52.3 µM at 24 and 48 h time intervals respectively. The growth inhibitory effects of dehydrocostus lactone were found to be due to loss of mitochondrial membrane potential, the induction of apoptosis and sub-G1 cell cycle arrest. CONCLUSIONS: Dehydrocostus inhibits in vitro gastrinoma cancer cell growth and therefore may prove beneficial in the management of gastrinoma cancer.

Acute phase serum cathepsin S level and cathepsin S/cystatin C ratio are the associated factors with cerebral infarction and their diagnostic value for cerebral infarction.

Cathepsin S plays an important role in the pathogenesis of several cardiovascular diseases; however, the relationship between serum cathepsin S and cerebral infarction (CI) is still unknown. This study aimed to investigate the relationship between acute phase serum cathepsin S level and cerebral infarction. A total of 202 stroke patients were enrolled into this study, and were divided into cerebral infarction (n = 140) group and non-cerebral infarction group (non-CI, n = 62). Fifty healthy individuals were recruited as the control group. Serum levels of cathepsin S and cystatin C were measured at days 1, 7, and 14 posthospitalization. Compared to the non-CI group, the CI group had significantly higher rates of hypertension, dyslipidemia, and smoking (all P < 0.05). The CI group had significantly higher cathepsin S levels and cathepsin S to cystatin C ratio (CatS/CysC) at both days 1 and 7 posthospitalization (both P < 0.05). Multivariate logistic regression analysis demonstrated that cathepsin S level (day 7) and CatS/CysC (days 1 and 7) were the associated factors with CI (all P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the Area Under Curve (AUC) value of CatS-day7, CatS/CysC-day1, and CatS/CysC-day7 were 0.726 (95% CI: 0.652-0.800, P < 0.001), 0.641 (95% CI: 0.559-0.723, P = 0.001), and 0.721 (95% CI: 0.645-0.797, P = 0.039), respectively. Cathepsin S and CatS/CysC were associated with acute CI, and may have the potential to be the diagnostic biomarkers for CI. Our findings help to better understand the role of serum cathepsin S level in CI.

Self-cross-linked melamine-formaldehyde-pectin aerogel with excellent water resistance and flame retardancy.

Self-cross-linked aerogel based on pectin and melamine-formaldehyde resin (MF) was fabricated via freeze-drying method using water as solvent, where pectin is structural material meanwhile acting as acid to catalyse the cross-linking of MF. The cross-linking reaction easily occurs without additional additives, which can be significantly accelerated at elevated temperatures, with a critical value of about 55 °C. The obtained aerogel shows network microstructures as observed with SEM. With increasing pectin content, the aerogel shows significantly increased compressive modulus. The compressive modulus of M10Pe5 arrives 23.2 MPa, the specific modulus of which arrives 188 MPa cm3/g, while pure MF aerogel are too fragile to keep intact after freeze-dried. The resulting aerogel has good thermal stability, excellent water resistance (can be second dried with limited strength loss) and low flammability. This partially bio-based novel aerogel with impressive properties is promising in many applications.

The effects of imidacloprid combined with endosulfan on IgE-mediated mouse bone marrow-derived mast cell degranulation and anaphylaxis.

Low levels of endosulfan are known to stimulate mast cells to release allergic mediators, while imidacloprid can inhibit IgE-mediated mast cell degranulation. However, little information about the effects of both pesticides together on mast cell degranulation is available. To measure the effects, IgE-activated mouse bone marrow-derived mast cells (BMMCs) were treated with imidacloprid and endosulfan, individually, and simultaneously at equi-molar concentrations in tenfold steps ranging from 10-4 to 10-11 M, followed by measuring several allergy-related parameters expressed in BMMCs: the mediator production and influx of Ca2+, the phosphorylation content of NF-κB in the FcεRI signaling pathway. Then, the effects of the mixtures on IgE-induced passive systemic anaphylaxis (PSA) of BALB/c was detectded. This study clearly showed that the application of equi-molar mixtures of both pesticides with 10-4-10-5 M significantly inhibited the IgE-mediated mouse bone marrow-derived mast cells degranulation in vitro and 10-4 M of them decreased IgE-mediated PSA in vivo, as the application of imidacloprid at the same concentration alone did. Morever endosulfan alone had no remarkable stimulatory effects on any of the factors measured. In conclusion, simultaneous application of equi-molar concentrations of both pesticides generally showed highly similar responses compared to the responses to imidacloprid alone, suggesting that the effects of the mixture could be solely attributed to the effects of imidacloprid.

Simultaneous detection of IgG and IgM antibodies against a recombinant polyprotein PstS1-LEP for tuberculosis diagnosis.

BACKGROUND: Commercial serological tests for the diagnosis of tuberculosis (TB) show poor sensitivity and specificity, and a new approach to antigen screening is required to improve the accuracy of serodiagnosis. METHODS: Using an indirect enzyme-linked immunosorbent assay (ELISA), we evaluated the responses of IgG and IgM antibodies to the recombinant PstS1-LEP protein expressed in Escherichia coli, a polyprotein of PstS1 and line multi-epitopes polypeptide (LEP). RESULTS: The mixture of anti-human IgG and IgM added to a well [Ig(G + M)], which was different from the combination of IgG and IgM (IgG + IgM), had a stronger immunoreactivity to PstS1-LEP than the single antibody. IgG and Ig(G + M), but not IgM against the PstS1-LEP protein effectively distinguished TB patients from patients with nontuberculous pulmonary disease (NTBPD) and healthy controls (HCs). Compared with IgG, the sensitivities of Ig(G + M) and IgG + IgM varied from 71.4% to 77.6% and 72.7% in pulmonary TB (PTB) patients and from 42.1% to 64.0% and 55.8% in extrapulmonary TB (EPTB) patients, respectively. The specificity of Ig(G + M) did not decrease, and was higher than that provided by IgG + IgM in HCs with positive tuberculin skin test. CONCLUSION: These findings suggest that PstS1-LEP can act as a candidate for detecting Ig(G + M) in serum from PTB and EPTB patients.

Preparation and characterization of anti-GP73 monoclonal antibodies and development of double-antibody sandwich ELISA.

BACKGROUND: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. MATERIALS AND METHODS: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. RESULTS: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). CONCLUSIONS: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.

Investigation of microRNA-155 as a serum diagnostic and prognostic biomarker for colorectal cancer.

The aim of the present study was to explore serum microRNA-155 (miR-155) expression in patients with colorectal cancer (CRC) and examined the potential usefulness of this molecule as a biomarker for diagnosis and prognosis in CRC. Serum samples were obtained between May 2007 and March 2013 from 146 CRC patients and 60 healthy controls. Serum miR-155 expression levels were measured by quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR). Survival curves were obtained using the Kaplan-Meier method and assessed by the log-rank test. The receiver operating characteristic (ROC) curve was used for the prediction of cut-off values of the markers. Serum miR-155 expression level on average was upregulated in CRC patients compared with the matched healthy controls (P < 0.001). ROC curve analysis showed that miR-155 was a useful marker for discriminating cases from healthy controls, with an area under the ROC curve (AUC) of 0.776 (95% confidence interval (CI) 0.714 to 0.837, P < 0.001). Kaplan-Meier analysis with the log-rank test indicated that high serum miR-155 expression had a significant impact on overall survival (38.2 vs. 69.9%; P < 0.001) and progression-free survival (34.8 vs. 66.0%; P < 0.001). In conclusion, the detection of miR-155 levels in the serum might serve as a new tumor biomarker in the diagnosis and assessment of prognosis of CRC.

Efficacy and toxicity of adding cetuximab to chemotherapy in the treatment of metastatic colorectal cancer: a meta-analysis from 12 randomized controlled trials.

Cetuxiamb, a monoclonal antibody against epidermal growth factor receptor (EGFR), has been used in combination with chemotherapy for patients with metastatic colorectal cancer (mCRC). However, the efficacy of combined therapies of cetuximab and different chemotherapy regimens remains controversial. Therefore, we conducted a meta-analysis to evaluate the efficacy and toxicity of adding cetuximab to oxaliplatin-based or irinotecan-based chemotherapeutic regimens for the treatment of patients with mCRC with wild-type/mutated KRAS tumors. Randomized controlled trials (RCTs), published in Pubmed and Embase were systematically reviewed to assess the survival benefits and toxicity profile mCRC patients treated with cetuximab plus chemotherapy. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicities. Results were expressed as the hazard ratio (HR) with 95 % confidence intervals (CI). Pooled estimates were generated by using a fixed-effects model or a randomized-effects model, depending on the heterogeneity among studies. A total of 12 trials involving 6,297 patients met the inclusion criteria and were included in this meta-analysis. All patients were administered oxaliplatin-based or irinotecan-based chemotherapy with or without cetuximab. Pooled results showed that the addition of cetuximab did not significantly improve the OS (HR = 0.99, 95 % CI = 0.89-1.09; Z = 0.28, P = 0.78) or PFS (HR = 0.94, 95 % CI = 0.81-1.10; Z = 0.76, P = 0.49), but did improve ORR (RR = 1.34, 95 % CI = 1.08-1.65; Z = 2.72, P = 0.00), when compared with chemotherapy alone. Subgroup analysis showed the highest PFS benefit in patients with wild-type KRAS tumors (HR = 0.80, 95 % CI = 0.65-0.99; Z = 2.1, P = 0.04) or wild-type KRAS/BRAF tumors (HR = 0.64, 95 % CI = 0.52-0.79; Z = 4.15, P = 0.00). When combined with cetuximab, irinotecan-based chemotherapy was significantly associated with prolonged PFS (HR = 0.79, 95 % CI = 0.66-0.96; Z = 2.36, P = 0.02) for all patients with differing gene-status. The incidence of grade 3/4 adverse events, including skin toxicity, diarrhea, hypertension, anorexia, and mucositis/stomatitis, was slightly higher in the combined therapy group than in the chemotherapy-only group. Based on the current evidence, the addition of cetuximab to chemotherapy significantly improves the PFS in patients with wild-type KRAS or wild-type KRAS/BRAF tumors as well as the ORR in all patients. In addition, irinotecan-based combination therapy showed a beneficial effect on the PFS in all patients. These findings confirm the use of cetuximab in combination with chemotherapy for the treatment of patients with mCRC with wild-type KRAS tumors. Further multi-center RCTs are needed to indentify these findings.

[A case of hemophagocytic lymphohistiocytosis syndrome caused by severe tuberculosis and literature review].

OBJECTIVE: To investigate the clinical features of a case of hemophagocytic lymphohistiocytosis syndrome (abbreviated as hemophagocytic syndrome, HPS) caused by severe tuberculosis and therefore to improve early diagnosis of this condition. METHODS: The clinical features and process of diagnosis and treatment of a case with HPS caused by severe tuberculosis in July 2011 were analyzed, and the reported literatures of the disease were reviewed. RESULTS: The patient was a 16-year-old male. The primary manifestations were fever, cough, abdominal distention and edema. Laboratory analysis indicated pancytopenia (WBC 3.0×10(9)/L, Hb 98 g/L, PLT 34×10(9)/L), liver dysfunction (ALT 51.5 U/L, AST 211 U/L, TBIL 20 µmol/L, DBIL 17.6 µmol/L), coagulation abnormalities (extension of TT and APTT, FIB 0.56 g/L), high level of ferritin (662 µg/L), and hemophagocytosis in bone marrow. Sputum smear was positive for tubercule bacillus. After 2 months of antituberculous therapy with ethambutol, streptomycin and sodium aminosalicylate, along with administration of prednisolone, human immunoglobulin, and thymic peptide α(1), the patient's body temperature, function of coagulation and liver abnormalities all returned to normal, and repeated sputum smears became negative. CONCLUSIONS: Tuberculosis is a cause of reactive hemophagocytic syndrome. Patients with hemophagocytic symptom should be rigorously screened for tuberculosis, and antituberculous therapy should be initiated early to improve prognosis.

[Effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in ahypercholesterolemic rabbit model.].

OBJECTIVE: To investigate the effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in a hypercholesterolemic rabbit model. METHODS: Thirty four male New Zealand white rabbits were randomized into four groups including normal control group (n = 6), placebo group (n = 8), atorvastatin group (1.5 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10) and montelukast group (1 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10). Rabbits except those in normal control group were fed a high cholesterol diet for 12 weeks. Serum lipids were measured at 0, 8 and 12 weeks after intervention. The intima/media ratio, percentages of macrophages or smooth muscle cells in intima and the expression of MCP-1 mRNA were examined. RESULTS: Atherosclerosis was evidenced in placebo group and atorvastatin or montelukast treatment significantly reduced neointima (0.32 +/- 0.12 and 0.34 +/- 0.10 vs. 1.12 +/- 0.36, P < 0.05) and macrophage content [(9.8 +/- 4.6)% and (11.2 +/- 3.7)% vs. (34.6 +/- 8.8)%, P < 0.05], increased SMC content [(18.6 +/- 6.9)% and (19.2 +/- 8.6)% vs. (5.2 +/- 2.3)%, P < 0.05] and inhibited expression of MCP-1 mRNA (0.42 +/- 0.08 and 0.40 +/- 0.06 vs. 2.36 +/- 0.48, P < 0.01). Montelukast had similar anti-atherogenetic effects as atorvastatin but had no influence on plasma lipids. CONCLUSIONS: Montelukast could attenuate atherosclerosis in this hypercholesterolemic rabbit model which might be attributed to its anti-inflammatory effects.

[Retinoic acid diminished the expression of lung tissue matrix metalloproteinase-2 and matrix metalloproteinase-9 in hyperoxia-exposed premature rats through regulating mitogen-activated protein kinases].

OBJECTIVE: To further investigate the protective effect of retinoic acid (RA) on hyperoxia induced lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs). METHODS: Establishment of hyperoxia (85%) induced lung injury model of premature Sprague-Dawley (SD) rats: 21 d gestational age SD rat's fetuses (term = 22 d) were delivered by hysterectomy. Within 12 - 24 h after birth, the premature rat pups were randomly divided into 4 groups: Group I, air-exposed control group; Group II, hyperoxia-exposed group; Group III, air plus RA-exposed group, Group IV, hyperoxia plus RA-exposed group. Group I and III were remained in room air, and group II and IV were placed in 85% oxygen. The pups in Group III and IV were injected with RA (500 microg/kg, every day) intraperitoneally. The entire lung tissues of premature rat pups were collected at 4 d, 7 d and 14 d. The mRNA levels of MMP-2 and MMP-9 were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 and MMP-9 activities were measured by zymography. Western blot was used to detect phosphorylated and total nonphosphorylated form of ERKs, JNKs and p38. RESULTS: Exposure to oxygen for 4 d, 7 d, and 14 d resulted in increased mRNA levels of MMP-2 and MMP-9 compared with air-exposed control group (P < 0.01 for all). The mean protein levels of active MMP-2 and pro/active MMP-9 after exposure to O2 were higher than air control groups on each experimental day (P < 0.01 or < 0.05). The phosphorylated ERK1/2, JNK1/2 and p38 proteins in hyperoxia-exposed group increased markedly compared with air-exposed control group (P < 0.01 for all). The pups treated with RA in the hyperoxic environment expressed significantly lower mRNA levels of MMP-2 and MMP-9 than the hyperoxic control pups on each experimental day (P < 0.05 for all). The levels of active MMP-2 and pro/active MMP-9 decreased to a different degree after RA treatment in hyperoxia exposure rat pups. In addition, RA treatment led to a decrease of p-JNK1/2 and p-38 (P < 0.01 for all) protein levels and a further elevation of p-ERK1/2 compared with hyperoxia-exposed group. CONCLUSION: Hyperoxia exposure elevated the expression of MMP-2 and MMP-9 markedly, which played a role in oxygen-induced lung injury. RA could have a protective effect on hyperoxia induced lung injury by decreasing active levels of JNK and p38, which subsequently reduce the expression and activation of MMP-2 and MMP-9.