Immune checkpoint inhibitors have become an important alternative for advanced non-small cell lung cancer (NSCLC) patients to surgery, chemotherapy, radiotherapy and targeted therapy. Monoclonal antibodies directed against immune checkpoint have shown better results in the application of first- or second-line treatment of NSCLC and for both squamous and non-squamous cell carcinoma patients, especially for those with positive PD-L1 tumor cells. Some comments will be made in present paper about the efficacy, biomarker, combined therapy and the resistant mechanism of immune checkpoint inhibitors.

Objective To investigate the effect of ginsenoside-Rgl on paraurethral fascia fibroblastsmultiplication and the expression of proliferation cell nuclear antigen (PCNA) of stress urinary incontinence(SUI) women in vitro. Methods Specimens of human paraurethral fascia were obtained from 4 SUI womenduring tension-free vaginal tape (TVT) or tension-free vaginal tape-obturator (TVT-O) procedure.Fibroblasts were isolated and cultured by outgrowth technique. After reaching confluency fibroblasts weresubcultured every 5 days and cells after passage number 3 to 5 were used for assessment. The paraurethralfascia fibroblasts were treated with ginsenoside-Rgl at different concentrations (5, 10, 20 μmol/L) andfibroblnsts without Rgl were used as controL The multiplication conditions of paraurethral fascia fibroblastswere respectively detected by methyl thiazolyl tetrazolium (MTr) assay and the expression of PCNA byhistochemistry. Results ( 1 ) Compared with the control group, the growth rate of cells treated with differentconcentrations of Rgl after 72h [ (29±5 )%, (40±5 )%, (26±4)% respectively ] was significantly higher(P<0.01). (2)Compared with the control group, the stimulatory effect of Rgl on fibroblast growth wassignificant at 24 h (P<0.01), and peaked at 72 hi (29±5)% ,(40±5)%, (26±4)% respectively, P<0.01]. (3)Compared with the control group(28.77% ), there was a significant increase of PCNA-positivecells (P<0.01) after 48 h treatment with different concentrations of Rgl (49.24%, 83.48%, 54.50%respectively). Conclusion The results indicate that, at least in vitro, fibroblasts from paraurethral fasciataken from women suffering from SUI are able to proliferate after

Central nervous system ( CNS) injuries, such as cerebral ischemia, traumatic brain injury (TBI), and spinal cord injury (SCI), are often accompanied by complex pathological changes, and could lead to a variety of other neurological diseases.Neurons and glial cells are precisely regulated by many genes.MicroRNA ( miRNA ) are endogenous molecules discovered in recent years that regulate post transcriptional gene expression.They are highly expressed in the central nervous system and abnormal expressed under pathological conditions.They are involved in regulating variety of pathological processes after CNS injuries, and are CNS disease potential biomarkers.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can be induced to differentiate into neuron-like cells in new environment after transplantation, and then to replace damaged cells for reconstructing neural circuit. OBJECTIVE: To establish the co-culture system between rat BMSCs and neural cells in vitro, and to study the influence of neural cells on the differentiation of BMSCs into neuron-like cells in the co-culture system. METHODS: The neural cells obtained from Wistar rat fetal brain tissue and BMSCs gained from rat thighbone were co-cultured in Transwell culture plate. The morphological changes of BMSCs were observed and the special markers of neural cells in BMSCs were examined by immunofluorescence on the fifth day of the co-culture. The results were compared with control group which where BMSCs were alone cultured. RESULTS AND CONCLUSION: BMSCs in the neural cells co-culture system extended, were radial, connected each other. Neuron specific enolase immunoreactions showed positive results, showing neuron-like cells. The positive ratio of neuron specific enolase-positive cells was (33.0±10.5)%. However, BMSCs in the control group did not express neuron morphological character. Immunofluorescence exhibited that cells were negative for neuron specific enolase. These indicate that microenvironment provided by neurons improves the differentiation of BMSCs into neuron-like cells.

ObjectiveTo investigate the expression of heme oxygenase-1 (HO-1) in lung tissue of mice with acute paraquat poisoning, and discuss its pathological mechanism.Methods Fifty-eight healthy male mice were randomly divided into control group (n = 8) and poisoned group (n = 50). The mice in poisoned group were lavaged with 20% paraquat (50 mg/kg), and those in control group with equal amount of normal saline. The mice were sacrificed on the day of experiment in control group, and those in poisoned group at 6 hours and 1, 3, 7, 14 days after poisoning. The lung tissue was harvested to observe the changes in pathology of lung with hematoxylin and eosin (HE) staining. The positive expression of HO-1 was determined with immunohistochemistry, and the protein expression of HO-1 was determined with Western Blot. The contents of superoxide dismutase (SOD) and malonaldehyde (MDA) were determined.Results The mice showed shortness of breath and signs of exhaustion 1 hour after poisoning, getting worse on 3-5 days, but returned to normal 14 days after poisoning. Under the light microscope, it showed that the control group had no significant pathological changes in lung tissue. One day after the ingestion, pulmonary alveolar structure disorder, obvious hemorrhage, edema and infiltration of inflammatory cells were found. At 3 days, the pathological changes in the lung tissue were more pronounced. They were less pronounced on 7 days, and inflammatory changes disappeared on 14th day, but alveolar structure disorder remained. Immunohistochemical test showed that HO-1 was seldom expressed in the lung tissue, and a little amount was expressed in the mucosal epithelial cells of the airway in control group. It was shown that inflammatory cell and endothelial were mainly distributed in the mucosal epithelial cells of airway 1 day after poisoning followed by a gradually decrease tendence, and came to normal level of control group 7 days after poisoning. It was shown by Western Blot that HO-1 (gray value) in lung tissue increased 6 hours after poisoning (2.438±0.467 vs. 0.475±0.167,P< 0.01), peaked at 1 day (9.200±0.940 vs. 0.475±0.167,P< 0.01), continued to increase till 7 days after poisoning, and it lowered to normal level thereafter (0.825±0.260 vs. 0.475±0.167,P> 0.05). The SOD activity (μU/L) in lung tissue was lowered 6 hours after poisoning, and it was significantly lower than that of control group (649.681±13.951 vs. 1 167.051±15.744,P< 0.01), and it continued to decrease up to 14 days after poisoning (859.733±121.079 vs. 1 167.051±14.744,P< 0.01). MDA content (μmol/L) in the lung tissue homogenate was elevated 6 hours after poisoning with significant difference compared with that of the control group (4.542±0.266 vs. 3.705±0.176,P< 0.01). It peaked on day 1 (5.956±0.281 vs. 3.705±0.176,P< 0.01), then it declined and reached normal level 3 days after poisoning (4.134±0.168 vs. 3.705±0.176,P> 0.05).Conclusion HO-1 expression was increased significantly in lung tissue of mice with acute paraquat poisoning, which may be considered as an important protection mechanism against paraquat poisoning.

[Summary] A total of 1 510 subjects undergoing physical examination in the Central Hospital of Xuzhou were included in this study. According to the level of TSH, the subjects were divided into low TSH group(0. 30-0. 99 mIU/L,n=351), moderate TSH group(1. 00-1. 89 mIU/L, n=703), and high TSH group(1. 90-4. 80 mIU/L, n=456). Analysis of variance and linear regression were used for data analysis. The results showed that systolic blood pressure ( SBP) , diastolic blood pressure ( DBP) , triglyceride ( TG) , and high-density lipoprotein cholesterol( HDL-C) revealed significant differences among 3 group(P<0. 05 or P<0. 01). In the univariate linear regression model, serumTSHwithinthereferencerangewasnegativelyassociatedwithSBPandDBP(P<0.05orP<0.01),and positively associated with TG and HDL-C (P<0. 05 or P<0. 01). However, the correlations disappeared after adjustment for gender, age, body mass index, fasting plasma glucose ( FPG ) , and TG. In the multiple linear regression model, a significant negative correlation of TSH with SBP and FPG was found in males(P<0. 05).

Objective To investigate altered levels and clinical significance of serum miR-133a in patients with acute coronary syndrome ( ACS ) and stable coronary artery disease ( SCAD ) .Methods Retrospective study.Serum miR-133a levels were determined by TaqMan quantitative reverse-transcription PCR assay in 64 ACS, 62 SCAD patients who were admitted to Jinling Hospital from October 2011 to October 2012 and 70 normal controls who had contemporaneously visited Jinling Hospital for routine examination .The ACS and SCAD patients were diagnosed according to the European Society of Cardiology guidelines .Serum lipid/lipoprotein profiles , myonecrosis biomarkers and Gensini scores were also analyzed .The area under curve ( AUC) and 95%confidence interval ( CI) were calculated using ROC analyses .The odds ratio ( OR) and 95%CI were calculated using the multivariate logistic regression analyses .Results Compared with the controls [ΔCt:1.00 ±0.05], serum miR-133a levels were significantly increased in both ACS [ΔCt:2.34 ±0.24] (t=6.059, P<0.001) and SCAD [ΔCt:1.45 ±0.13] (t=3.265, P=0.001) patients.The miR-133a levels in ACS patients were significantly higher than in SCAD patients (t=3.133, P=0.002). Serum miR-133a were positively correlated with levels of creatine kinase MB ( CK-MB) ( r=0.402, P<0.001), cardiac troponin I (cTNI) (r=0.410, P=0.001) and Gensini scores (r=0.438, P<0.001). ROC curve analyses showed that the AUC of miR-133a for differentiating coronary artery disease (CAD) and controls was 0.717 (95%CI:0.645-0.788, P<0.001) and the AUC for differentiating ACS and SCAD was 0.667 (95% CI:0.573-0.761, P=0.001).Logistic regression analyses revealed that high miR-133a levels were closely associated with the presence of ACS ( OR=6.00, 95% CI:1.93 -18.67, P=0.002) and SCAD (OR=2.81, 95%CI:1.03-7.68, P=0.044), and also had statistical significance for differentiating ACS and SCAD (OR=2.13, 95% CI:1.20-3.78, P=0.010), after adjustment for the age, gender and serum lipid/lipoprotein levels.Conclusions Serum miR-133a levels were significantly elevated in CAD patients, and ACS patients exhibited the more significant increase .Serum miR-133a may be function as the potential biomarker for the disease assessment and judgement .

Objective To explore the correlation of the gene polymorphism of the two single nucleotide polymorphisms(SNPs)rs1443434andrs925489onforkheadboxEl(FOXE1)withthehighnormalthyroidstimulating hormone ( TSH) level in Chinese Han population. Methods 1 400 subjects with normal serum TSH and thyroid peroxidase antibody(TPOAb) levels were included. According to TSH or TPOAb levels, the subjects were divided into high normal TSH group(H-TSH group,n=195) and normal TSH control group(TSH control group,n=1 205) or high normal TPOAb group ( H-TPOAb group, n=711 ) and low normal TPOAb group ( L-TPOAb group, n=689 ) , respectively. The genotypes on the two SNPs of all the subjects were performed by whole-genome genotyping chips. Results There were significant differences in rs925489 genotypic distributions and allele frequencies between H-TSH group and TSH control group(both P<0. 05). The genotype TT and allele T in H-TSH group were significantly higher than those in TSH control group(89. 75% vs 83. 15%, 94. 62% vs 91. 29%). The normal TSH levels were positively associated with rs925489 genotypic distributions after adjustment for sex, age, and high density lipoprotein cholesterol(P<0. 01). There were no significant differences in rs1443434 genotypic distributions and allele frequencies between two TSH groups or two TPOAb groups. Conclusion FOXE1 rs925489 gene polymorphism may be correlated with the high normal TSH level in Chinese Han population.

Aim To explore the potential mechanism of ulinastatin’s antioxidant effect by examining the Nrf2 /HO-1 pathway.Methods OVA-induced asthma of mice was cured by intraperitoneal injection of ulinas-tatin (1 00 kU·kg -1 ·d -1 ).Control mice were given the same volume of PBS (pH 7.4).To investigate the effect of ulinastatin on airway hyperresponsiveness, levels of interleukin IL-4,IFN-γand OVA specific IgE in bronchoalveolar lavage fluid (BALF)were measured using enzyme-linked immunosorbent assays (ELISAs). The content of ROS from BALF of mice was tested in double hydrogen rhodamine (DHR)-1 23 method.The level of protein carbonyl and MDA from lung tissue of mice was detected with Protein carbonyl content assay kit and MDA kit.And antioxidative enzyme in mice BALF was tested by antioxidant enzyme kit.The levels of HO-1 in lung tissue from mice were detected by Western blot and Real-time PCR.Nuclear transfer and binding activity of Nrf2 were tested respectively by Western blot,IF and EMSA.Results Ulinastatin could alleviate the airway hyperresponsiveness,dis-tinctly reduce the content of IL-4,OVA specific IgE, ROS,protein carbonyl and MDA,but upraise the ex-pression of IFN-γand antioxidative enzyme such as SOD,GSH and TAOC. Moreover, the antioxidant effect of ulinastatin could be reversed by Znpp,which was the inhibitor of HO-1 .Ulinastatin could obviously induce the expression of HO-1 in protein level in a dose-and time-dependent manner.Ulinastatin could also induce the nuclear transfer of Nrf2 and increase the binding activity of Nrf2 as well as the expression of HO-1 in gene level;Conclusion Ulinastatin could induce the activation of Nrf2 /HO-1 pathway,which may contribute to the protective effects of ulinastatin a-gainst OVA-induced oxidative stress.

Objective To investigate the characteristic changes of the metabolism products in the auditory cortex (transverse temporal gyrus) in diabetes combined with nerve deafness using 1 H magnetic resonance spectros‐copy (1 H -MRS) ,and to discover the early warning indicator of nerve deafness in type 2 diabetes .Methods PTA was performed in 98 patients with type 2 diabetes (diagnosed by Endocrinology Department) ,and in 15 healthy sub‐jects in the control group .The patients were classified into four groups :the group of type 2 diabetes;type 2 diabe‐tes with unilateral and bilateral deafness ,and the normal control group .Cerebral metabolism was studied by assess‐ing the ratios of nitro -acetyl aspartate contrast to choline (NAA/Cho) as well as to creatine (NAA/Cr) ,myo-in‐ositol to creatine (mI/Cr) and choline to creatine (Cho/Cr) ratios in the auditory cortical separately in these groups . The Pearson correlation analysis was applied to determine blood glucose value with the nerve metabolites while the ROC curves were made for those metabolism markers to find the best diagnostic threshold .Results NAA/Cr and NAA/Cho were negatively correlated with AHI index and Cho/Cr ,mI/Cr was positively correlated with blood glu‐cose value .Significantly lower values of NAA/Cho ratio were found in patients'(diabetes without deafness) auditory cortex compared with 15 age-matched control subjects (P<0 .05) .NAA/Cr and NAA/Cho ratio in diabetes with deafness were significantly lower than those in control group (P< 0 .05) ,Cho/Cr higher than those of in other groups (P<0 .05) .NAA/Cr and NAA/Cho ratio in injured and uninjured auditory cortex of diabetes with unilateral deafness were significantly lower than those of in control group (P<0 .05) ,then we made a self -comparison be‐tween the injured and uninjured auditory cortex ,finding that NAA/Cho ratio had a significant difference .All of the metabolisms were tested by the curve of ROC .The area of NAA/Cho under the ROC curve was 81% ,which had a higher accuracy .NAA/Cho equal to 1 .65 can be used as boundary indicators between diabetes without deafness and diabetes with deafness groups ,the areas of the remaining indicators under the ROC curve was<50% .Conclusion NAA/Cho may be the early warning marker of nerve deafness in type 2 diabetes .