AIM and METHODES: To evaluate the possible signal transduction mechanism of nontargeted mutagenesis in vero cells induced by DNA damaging agent N-methyl-N-nitro-N-nitrosoguanidine(MNNG),the activation of c-Jun NH 2-terminal kinase/stress activated protein kinase(SAPK/JNK) pathway in vero cells induced by MNNG was studied. Western Blot analysis and Solid-phase kinase assay were used to measure the phosphorylation of JNK1 and kinase activity of JNKs, respectively. RESULTS: After 0.2 ?mol/L, 2.5 h MNNG or 1 mg/L, 1 h cycloheximide (CHM) treatment, the proportion of phosphorylated JNK1 in cell extract increased significantly, simultaneously the kinase activity of JNKs increased dramatically(6.7 and 3.0 folds respectively), as measured by the phosphorylation of c-Jun, a substrate of JNKs. CONCLUSION: Both 0.2 ?mol/L 2.5 h MNNG and 1 mg/L 1 h CHM treatment can induce the activation of JNK/SAPK pathway, one of the stress signal transduction pathways, in vero cells.

0.05),and TRAF2 was related to the tumor grade only(P

AIM:To observe the protective effect of nicorandil on myocardial ischemia reperfusion injury in patients undergoing valve replacement.METHODS:Sixty patients undergoing valve repalacement were randomly divided into 3 groups:control(Ⅰ)group,nicorandil delayed precondictioning(Ⅱ)group and nicorandil preconditioning(Ⅲ)group.20 mg nicorandil was given i.v.24 h before operation in group Ⅱ,whereas in group Ⅲ,20 mg nicorandil was given i.v.after induction of anesthesia.Blood samples were taken from coronary venous for determination of cTnI,TNF-?,IL-6 levels at aortic clamping(T0),15 min(T1),30 min(T2),60 min(T3),90 min(T4)after aortic declamping.Right atria myocardium tissue were taken at T0 and T2 to observe the histopathological changes with electron microscopy.RESULTS:The levels of cTnI,TNF-?and IL-6 in group Ⅱand Ⅲ were significantly lower than those in group I.Myocardium injury was obviously lighter in groupⅡand Ⅲ than that in group Ⅰ,whereas the levels of cTnI,TNF-?,IL-6 and myocardium injury were lower in group Ⅱ than those in group Ⅲ.CONCLUSION:Nicorandil is effcetive in decreasing myocardial ischemia repefusion injury in patients undergoing valve replacement,The protective effect of nicorandil delayed preconditioning is more obvious than precondictioning.

Objective:To study the effect of rotational errors on the positioning accuracy (PA) and to assess whether correcting rotation in patients with head-neck tumors in radiotherapy or not.Methods:The image information of 34 patients with head-neck tumors treated at Zhongnan Hospital of Wuhan University between August 2019 and January 2020 was collected. Mega-voltage computed tomography (MVCT) images of each patient were taken before radiotherapy, and were registered with planned kilo-voltage computed tomography (KVCT) images by two registration methods. All information was divided into control group (translation only) and intervention group (translation and rotation) according to different registration methods, there were 144 fractioned registered images for each group, respectively. The position errors of the two registration methods were recorded and compared. Data were carried out with Wilcoxon signed rank test and Spearman rank correlation.Results:Translational errors of the control group and the intervention group were 0.10 (5.35) mm and 0.00 (5.78) mm in right-left direction, and there was a statistically significant difference ( Z=-2.675, P=0.007); 0.75 (2.78) mm and 0.60 (2.68) mm in superior-inferior direction, and there was a statistically significant difference ( Z=-2.819, P=0.005); 0.10 (0.90) mm and 0.20 (1.28) mm in anterio-posterior direction, and there was a statistically significant difference ( Z=-3.984, P<0.001). Rotational errors of the intervention group were -0.20 (0.60)°, 0.35 (2.00)°, 0.00 (0.98)° in pitch, roll, yaw, respectively. The distribute of 3D vector corrected frequency for two groups was positively skewed. The corrected cumulative frequency (CCF) varied with 3D vector, 3D vector was 8.0 mm, and 19 F and 16 F fractioned treatments of the control group and the intervention group were not corrected, respectively; 3D vector was between 8.0-13.5 mm, the corrected tendency of the intervention group was slower and fractioned treatment was completed later. The analytical results of Spearman rank correlation showed that rotational errors in pitch were negatively correlated with translational errors of the control group in superior-inferior direction ( r=-0.182, P=0.029) and the intervention group in anterio-osterior direction ( r=-0.484, P<0.001); rotational errors in roll were negatively correlated with translational errors of the intervention group in right-left direction ( r=-0.334, P<0.001); rotational errors in yaw which were positively correlated with translational errors of the intervention group in right-left direction ( r=0.370, P<0.001) were negatively correlated with translational errors of the control group in superior-inferior direction ( r=-0.171, P=0.040) and the same was true for the intervention group ( r=-0.203, P=0.015); total angles were positively correlated and negatively correlated with translational errors of the control group in superior-inferior direction ( r=0.246, P=0.003) and anterio-posterior direction ( r=-0.188, P=0.024), and positively correlated with 3D vector of the control group ( r=0.198, P=0.017), total angles were positively correlated with translational errors of the intervention group in superior-inferior direction ( r=0.170, P=0.041) and with 3D vector of the intervention group ( r=0.239, P=0.004); there were no correlations between rotational errors and the other translational errors (all P>0.05). Conclusion:Although the corrected rotation increases translational errors in anterio-posterior direction and 3D vector, it improves PA for head-neck tumors in radiotherapy. When rotational errors are not corrected, rotational offsets are present with corrected translation to decrease its effect on PA.

Objective:To establish the quality standard for Naoxin Luotong pills. Methods:Astragali radix, bombyx batryticatus and scorpio were identified under a microscope. Peach kernel, astragali radix, paeoniae radix alba, rheum, paeonia suffruticosa and salvia miltiorrhiza were identified by TLC. The content of total ferulic acid was determined by HPLC with a Sapphire C18 column (250 mm × 4. 6 mm,5 μm). The mobile phase was acetonitrile-0. 1% phosphoric acid(12 ∶88)and the detection wavelength was 316 nm. The column temperature was 35℃ and the flow rate was 1. 0 ml·min-1 . Results:The microscopic characteristics of astragali radix, bombyx batryticatus and scorpio were obvious to be observed easily. The TLC spots of peach kernel, astragali radix, paeoniae radix al-ba, rheum, paeonia suffruticosa and salvia miltiorrhiza were clear and specific. Ferulic acid had a good linear relationship within the range of 5. 1-81. 6μg·ml-1(r=0. 999 9), and the average recovery was 103. 30% with RSD of 1. 96% (n= 9). Conclusion:The standard can be used for the quality control of Naoxin Luotong pills.

Objective To evaluate the value of MR in the diagnosis of primary splenic lymphoma (PSL).Methods The MR imaging features of 3 PSL cases proved by pathology were retrospectively reviewed. Results Three cases were all pathologically diagnosed as B-cell non-Hodgkin's lymphoma(NHL). Two cases were multiple node shape and one was massive shape. Unenhanced MR imaging revealed heterogeneous splenic enlargement, with large nodules showing iso-hyperinternse on T1WI and hypointense on T2WI. Linear hyperintense on T1WI and T2WI was seen on the spleen peripherous. The spleen vascular was infiltrated. CE-MRI showed heterogeneous enhancement of spleen with iso-hypointense. The focus of postperitoneal showed medial enhancement. Immunohistochemistry-showed 2 cases of diffuse B cell. The CD20 and CD19 α of tumor cell showed diffuse( + ) ,CD3 ,CD5 individual( + ) ,CD43 ( + ) ,CD45RO( + ), CD10 ( +/- ), Mum ( + ), MAC387 individual ( + ), 1 case of B lymphocell type, CD79α ( + ) ,CD23( + ) ,CD38( + ) ,λ( + ). Conclusion The MR imaging features of PSL were characteristic and helpful in the diagnosis of PSL, but the correct diagnosis was still dependent on the pathology and immunohistochemical staining.

We detected the isoniazid resistance in clinical Mycobacterium tuberculosis isolates by high-resolution melting (HRM) curve analysis and assessed the application value of the assay.The isoniazid resistance of 49 M.tuberculosis isolates preserved in laboratory was analyzed by the drug sensitivity test (traditional proportion method).Further analysis was made on the sequencing of the isoniazid resistance determining region in these test strains,and their mutation sites were screened.Specific primers used in the HRM curve analysis were designed based on the screened mutation sites,DNA mutations were assayed in the isoniazid-resistant gene determining region by the HRM curve analysis,and an assessment was made of the detection efficiency of the assay in isoniazid resistance in M.tuberculosis.Results of the drug sensitivity test (proportion method) showed that,of the 49 test strains,there were 20 isoniazid-resistant strains,29 isoniazid-sensitive strains.Results of the sequencing analysis showed that:1) KatG gene had four mutation patterns,i.e.,point mutations at site 234,at sites 234 and 315,at sites 234 and 463,and at sites 234,315 and 463;2) there were three mutations were detected in inhA gene,i.e.,mutations in inhA-8,-15 and-152.Analysis of gene mutation in drug-resistant strains found that of the 20 isoniazid-resistant strains,11 (55 ％) were mutated at codon 315 of KatG gene;6 (30％) were mutated in inhA-15 (4/20),-8 (1/20) and-153 (1/20) of inhA gene;two (10％) were mutated at codon 315 of KatG gene and in inhA-15;in one strain (5％),no mutation was detected in KatG and inhA genes.Through the gene mutation detection,the sensitivity and specificity of isoniazid resistance in M.tuberculosis were 95 ％ and 100 ％,respectively.Results of HRM curve analysis of drug-resistance gene mutations in test strains showed gene mutations were present in 18 strains and absent in 24 ones;referring to DNA sequencing results,the sensitivity and specificity of the assay were 94.7％ and 80％,respectively.Judged by mutations as drug-resistance via the HRM curve analysis,19 resistant and 24 sensitive strains were tested.With the drug sensitivity test results by the proportion method as controls,the sensitivity and specificity of the assay were 95 ％ and 82.76 ％,respectively.Use of the HRM curve in the detection of resistance of M.tuberculosis to isoniazid is characterized by good sensitivity and short time consuming,and has certain value in the rapid diagnosis of isoniazid-resistant tuberculosis.

Objective To assess the development,progression and change of nonmotor symptoms in patients with Parkinson' s disease and its impact on patients' quality of life.Methods Eighty-seven consecutive patients with idiopathic Parkinson' s disease were studied.Parkinsonian status was assessed at baseline and 3 years follow-up using Unified Parkinson' s Disease Rating Scale (UPDRS) part Ⅲ & Ⅳ,Nonmotor Symptoms Questionnaire (NMSQuset),Parkinson-related quality of life (PDQ) scales.Paired ttest,Chi-square test,Spearman rank order correlation and hierarchical regression of the major statistical procedures were employed.Results At 3 years follow-up,compared to baseline,the UPDRS Ⅲ score (22.21 ±11.31 vs 30.49± 11.68),UPDRS Ⅳ score(1.00±1.54 vs 2.94±3.12),NMS score (7.98±3.96 vs 12.35 ± 5.12) and PDQ score (28.11 ± 22.88 vs 36.65 ± 26.95) were significantly higher ( t =- 5.54,- 5.75,- 6.46,- 5.29,all P =0.000,respectively).The aggravation of motor and nonmotor symptoms caused the decline of quality of life.The prevalence of constipation,problem of remembenng thing,nocturia ranked tops,and depression,and anxiety were still in the middle,compared with baseline.The prevalence of pains,sweating,dribbling,sense of incomplete emptying etc were significantly increased during the follow-up,△R2 were 21.6％ and 23.4％ respectively,resulting in the deterioration of quality of life.Conclusions PD nonmotor symptoms appear from the early stage.The motor and nonmotor symptoms aggravate over time.

OBJECTIVETo study the effects of 50 Hz power-frequency magnetic fields on signal transduction pathway of stress-activated protein kinase(SAPK), and explore the cellular signal transduction mechanism of the biological effects induced by power-frequency magnetic fields.

METHODSChinese hamster lung(CHL) cell line was exposed to power-frequency magnetic fields with two intensities for different exposure durations. The cytoplasmic protein was extracted and the phosphorylated portion of SAPK and SEK1/MKK4 was measured with Western blotting analysis. The SAPK enzymatic activity was measured by the solid-phase kinase assay in cells exposed to power-frequency magnetic fields for 15 min.

RESULTSBoth 0.4 mT and 0.8 mT power-frequency magnetic fields could enhance the phosphorylation of SAPK in a time-relative course manner, and reached the maximum extent at 15 min, with an increase of 20% and 17% respectively. The solid-phase kinase assay showed that the enzymatic activities of SAPK were also increased, which were 2.9 +/- 0.4 and 2.1 +/- 0.9 times of control respectively. However, the duration of SAPK phosphorylation induced by 0.8 mT was longer than that of 0.4 mT, while the duration and extent of SAPK dephosphorylation was remarkably shorter than that of 0.4 mT. The power-frequency magnetic fields under equal conditions could not phosphorylate(activate) the SEK1/MKK4.

CONCLUSIONPower-frequency magnetic fields could activate the SAPK, but not SEK1/MKK4. It is suggested that power-frequency magnetic fields may activate SAPK signal transduction pathway through a kinase other than SEK1/MKK4. The activation mechanism of SAPK of power-frequency magnetic fields needs to be identified in more detail.

Animals ; Cell Line ; Cricetinae ; Cricetulus ; Enzyme Activation ; radiation effects ; Lung ; metabolism ; radiation effects ; MAP Kinase Kinase 4 ; metabolism ; MAP Kinase Signaling System ; physiology ; radiation effects ; Magnetics ; Phosphorylation

Objective To study the safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection.Methods CNKI, Wanfang database , PubMed, Embase and Cochrane library were systematically searched.Randomized controlled trials about colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection were enrolled.The Cochrane Reviewers′Handbook 5.2 was employed to evaluate the quality of the enrolled studies. The primary outcome was all-cause mortality.The secondary outcomes included infection-related mortality, clinical response, bacterial clearance, nephrotoxicity and hepatotoxicity.Meta-analysis was conducted by RevMan 5.3 software.Results Seven articles containing 859 patients were finally included.There were no significantly statistical differences in all-cause mortality rate (relative risk [RR]＝1.07, 95%CI:0.93-1.24, P＞0.05), infection-related mortality rate (RR＝1.35, 95%CI:0.98-1.87, P＞0.05), bacterial clearance rate (RR＝0.85, 95%CI:0.71-1.02, P＝0.08), hepatotoxicity development rate (RR＝0.68, 95%CI:0.41-1.13, P＝0.14), and nephrotoxicity development rate (RR＝1.01, 95%CI:0.85-1.22, P＞0.05) between colistin monotherapy and combination therapy.The clinical response rate was higher in combination therapy than that in colistin monotherapy ( RR ＝0.81, 95%CI:0.66 -0.98, P ＝0.03).In the subgroup analysis, no statistical differences were found in all-cause mortality rate between colistin monotherapy and combination therapy for carbapenem-resistant Acinetobacter baumannii infection (RR＝1.00, 95%CI:0.86-1.12, P＞0.05). The dosage of colistin with or without loading dose was not associated with the treatment response .Conclusions Although colistin-based combination therapy has a better clinical response against carbapenem -resistant bacteria infection, especially for Acinetobacter baumannii infection, the mortality rate dose not decline compared to colistin monotherapy.Large-scale randomized controlled trials are needed to evaluate the effect in the future.