[Influence of genetic variation of programmed death-ligand 1 (PD-L1) on the prognosis of patients with non-small cell lung cancer who received platinum-based adjuvant chemotherapy].

Objective: The aim of present study was to investigate the influence of genetic variation of programmed death-ligand 1 (PD-L1) on the prognosis of patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Methods: This study was designed as a retrospective analysis, and a total of 278 patients with postoperative NSCLC who received platinum-based adjuvant chemotherapy from January 2012 to December 2018 in the Department of Respiratory Medicine of the First affiliated Hospital of Zhengzhou University were included in this study. Biological specimens of the patients were collected during hospitalization. Recurrence status and adverse reactions were evaluated in the hospital during adjuvant chemotherapy. Survival data of the patients were obtained through telephone follow-up after completing the fixed cycle of adjuvant chemotherapy. DNA extracted from the collected hematological specimens was genotyped for PD-L1 gene polymorphism. Additionally, postoperative cancer tissue specimens from 68 patients were collected for RNA extraction in order to perform the PD-L1 mRNA expression analysis. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis. Results: Prognostic results indicated that the median disease-free survival (DFS) of the 278 patients with NSCLC was 3.2 years and the median overall survival (OS) was 4.9 years. The prevalence of -1813G>C polymorphism were: GG genotype 173 cases (62.23%), GC genotype 92 cases (33.09%), CC genotype 13 cases (4.68%), the minor allele frequency was 0.21, the distribution of the three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.864). In view of the rare frequency of CC genotype, GC and CC genotype were merged in the following analysis. The survival analysis results of the two genotype groups suggested that the median DFS of patients with GG and GC/CC genotype was 2.7 and 4.0 years, which was statistically significant (P=0.013). Furthermore, the median OS of patients with GG and GC/CC was 4.0 and 5.4 years respectively, which was statistically significant as well (P=0.009). However, the safety analysis failed to find the significant association between the polymorphism and adverse events (P>0.05). Interestingly, expression analysis of RNA extracted from cancer tissues specimens indicated that the PD-L1 mRNA expression of the patients with GG genotype were significantly higher than those of the GC/CC genotype (3.67±0.65 vs 2.69±0.78, P<0.001). Conclusion: The prognosis of patients with postoperative non-small cell lung cancer who received platinum-based adjuvant chemotherapy is influenced by -1813G>C polymorphism of PD-L1 gene.

Treatment of vitiligo with 308-nm excimer laser: our experience from a 2-year follow-up of 979 Chinese patients.

BACKGROUND: The 308-nm excimer laser had been proved to be a time-efficient and potent therapeutic alternative for the management of vitiligo. Different results had been reported in different ethnic populations. OBJECTIVE: To investigate the efficacy and related contributing factors of 308-nm excimer laser in Chinese vitiligo patients. METHODS: A total of 979 Chinese patients (3478 lesions) with progressive-stage vitiligo who had received 308-nm excimer laser treatment were recruited from the vitiligo clinic of Shandong Provincial Hospital of Dermatology &Venereology from 2012 to 2014. Efficacy of treatment was evaluated at the end of session by two independent dermatologists based on the before and after images taken. Repigmentation was graded on a 4-point scale: grade 1, poor repigmentation (0-25%); grade 2, moderate repigmentation (26-50%); grade 3, good repigmentation (51-75%); grade 4, excellent repigmentation (76-100%). RESULTS: The mean grade of repigmentation was 2.29, 44.22% showed less than 25% repigmentation, 16.27% showed 26-50% repigmentation, 5.95% showed 51-75% repigmentation and 33.55% showed more than 76% repigmentation. The repigmentation of facial lesions was better than lesions located elsewhere (P < 0.0001), the best response was noted in the periorbital region, while lesions on hands and feet showed poor repigmentation (P < 0.0001). The degree of repigmentation was negatively correlated with disease duration (r = -0.268, P < 0.001), age (r = -0.095, P < 0.001) and shape of lesions (r = -0.114, P < 0.001), whereas it was positively correlated with treatment frequency (r = 0.270, P < 0.001). Lesions with concurrent poliosis were more likely resistant to treatments. CONCLUSION: 308-nm excimer laser appears to be an effective and safe treatment in Chinese vitiligo patients. The clinical response and treatment efficacy was affected by many factors such as age, affected anatomical area, shape of the lesion, disease duration and treatment frequencies.

CARD9 mutation linked to Corynespora cassiicola infection in a Chinese patient.

Corynespora cassiicola is a plant pathogen associated with leaf-spotting disease. The fungus has been found on diverse substrates: leaves, stems and roots of plants; nematode cysts and human skin. It rarely causes human infections. Here we report one case of subcutaneous phaeohyphomycosis caused by C. cassiicola with prominent tissue necrosis in a woman. All of her clinical features pointed towards a genetic linkage. Hence, whole-exome sequencing and Sanger sequencing were performed on this patient. One mutation of CARD9 was detected.

Dietary supplementation with Lactobacillus fermentum I5007 improves the anti-oxidative activity of weanling piglets challenged with diquat.

AIMS: To determine the effects of Lactobacillus fermentum I5007 on the redox state of piglets oxidatively stressed with diquat. METHODS AND RESULTS: Twenty-four, 28-day-old barrows were used in a 2 × 2 factorial design experiment with the main effects being Lact. fermentum supplementation and diquat challenge. Half of the pigs (n = 12) were orally administered with 20 ml of a solution containing 10(8 ) CFU ml(-1) of Lact. fermentum each morning of the 21-day trial, while the remainder received saline. On day 8, these two groups were further subdivided so that half of the pigs in each group (n = 6) were intraperitoneally injected with 10 mg kg(-1) BW diquat, while the remainder received saline. The diquat-injected pigs had significantly poorer performance and increased levels of plasma cortisol, adrenaline, carbonyl and malondialdehyde. Lactobacillus fermentum supplementation significantly increased superoxide dismutase and glutathione and increased the ability to inhibit superoxide anion production in liver and muscle. CONCLUSIONS: Lactobacillus fermentum improved the anti-oxidative defence system and alleviated damage caused by diquat. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus fermentum has the potential to alleviate oxidative stress and improve weaning pig performance.

Identification of two novel splice mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a rare, autosomal dominant dermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsa of the hands and feet. The DSH locus has been mapped to chromosome 1q21, and in 2003, pathogenic mutations were identified in the ADAR1 (adenosine deaminase acting on RNA1) gene. In this study, we performed mutation detection of the ADAR1 gene in two Chinese families with DSH. PCR and direct sequencing of the ADAR1 gene were used to identify and confirm the mutations in the two families. Furthermore, we analysed the RNA transcripts by reverse transcriptase (RT)-PCR. Two aberrant splice products were confirmed with RT-PCR and DNA direct sequence analysis. These novel findings further extend our understanding of the role of ADAR1 in DSH.

Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms.

BACKGROUND AND PURPOSE: Recent studies have shown that resveratrol increased endothelial progenitor cells (EPCs) numbers and functional activity. However, the mechanisms remain to be determined. Previous studies have demonstrated that increased EPC numbers and activity were associated with the inhibition of EPC senescence, which involves activation of telomerase. Therefore, we investigated whether resveratrol inhibits the onset of EPC senescence through telomerase activation, leading to potentiation of cellular activity. EXPERIMENTAL APPROACH: After prolonged in vitro cultivation, EPCs were incubated with or without resveratrol. The senescence of EPCs were determined by acidic beta-galactosidase staining. The bromo-deoxyuridine incorporation assay or a modified Boyden chamber assay were employed to assess proliferative or migratory capacity, respectively. To further examine the underlying mechanisms of these effects, we measured telomerase activity and the phosphorylation of Akt by western blotting. KEY RESULTS: Resveratrol dose dependently prevented the onset of EPCs senescence and increased the proliferation and migration of EPCs. The effect of resveratrol on senescence could not be abolished by eNOS inhibitor or by an oestrogenic receptor antagonist. Resveratrol significantly increased telomerase activity and Akt phosphorylation. Pre-treatment with the PI3K inhibitor, LY294002, significantly attenuated resveratrol-induced telomerase activity. CONCLUSIONS AND IMPLICATIONS: Resveratrol delayed the onset of EPC senescence and this effect was accompanied by activation of telomerase through the PI3K-Akt signalling pathway. The inhibition of EPCs senescence by resveratrol might protect EPCs against dysfunction induced by pathological factors in vivo and improve EPC functional activities in a way that may be important for cell therapy.

Incidence of changes and predictive factors for sexual function after coronary stenting.

The study was aimed at determining the incidence of changes in sexual function and identifying the possible associated variables of erectile dysfunction (ED) in coronary artery disease (CAD) patients undergoing coronary stenting. Four hundred and sixty-seven patients were retrospectively contacted with a questionnaire regarding sexual function from 6 months pre-stenting to 6 months post-stenting by telephone follow up. Univariate analyses were used to determine prognostic variables. ED changed following stenting in CAD (P < 0.05), in acute coronary syndrome (ACS) (P > 0.05) and in chronic coronary syndrome (CCS) (P < 0.05). Sexual activity was not resumed in 8.1%, was unchanged in 33.8%, increased in 0% and decreased in 58.0%. The average frequency of sexual activity decreased every month in CAD (P < 0.05), in ACS (P < 0.05) and in CCS (P < 0.01) after undergoing coronary stenting respectively. The mean time interval between the onset of ED and CAD was 33 months. Resuming sexual activity after stenting varied from 2 weeks to 30 months. Significant predictors of ED after coronary stenting were mean age, diabetes mellitus, 2,3-vessel disease or current smoking status. It was concluded that coronary stenting had a significant incidence of ED. Mean age, diabetes mellitus, 2,3-vessel disease or current smoking status showed to be the main variables associated with ED. Attempts to improve individual secondary prevention outcomes (controlling serum glucose and smoking cessation) should be designed.

Pro-EMAP II is not primarily cleaved by caspase-3 and -7.

Endothelial monocyte-activating polypeptide (EMAP) II is a unique cytokine, also known as p43, the active mature form of which exhibits antiangiogenic properties in vivo and in vitro. The proteolytic enzymes associated with the cleavage and release of the active mature form, however, remain unclear. Here we show that, in contrast to prior observations, purified pro-EMAP II is not cleaved by either caspase-3 or -7 in vivo or in vitro. Thus other proteolytic processes, which allow it to induce apoptosis via caspase-3 activation in migrating and dividing endothelium, may be involved in the release of the active mature EMAP II.

Effects of vitamin E on the blastogenic response of splenocytes and lipofuscin contents in the hearts and brains of aged mice.

Semipurified diets containing 30 or 500 ppm of dl-alpha-tocopherol (VE) were fed for 12 weeks to young (3-month-old) and old (20-month-old) Swiss mice. We measured the blastogenic response of splenocytes, the serum VE, and the lipofuscin levels in brains and hearts. We found that old mice fed with 500 ppm VE diet had a significantly higher serum VE level and blastogenic response of splenocytes to concanavalin-A (ConA) and lipopolysaccharide (LPS) than those fed with 30 ppm VE diet (p < 0.01). However, the lipofuscin level in the brains and hearts of aged mice declined substantially with the VE supplementation (heart: p < 0.001, brain: p < 0.05). Furthermore, the effects of dietary VE on the serum VE and tissue lipofuscin content in aged mice were much more obvious than in the young animals.

Effects of vitamins and methionine on blastogenic response of splenocytes and lipid peroxidation in lung and liver of mice exposed to SiO2 dust.

We studied the effects of nutrients such as vitamin C, E, B6, niacin, and methionine on the blastogenic response of splenocytes and lipid peroxidation (LPO) in lung and liver of mice exposed to SiO2 dust. The results showed that after treatment with SiO2, the blastogenic response of splenocytes decreased significantly (p < 0.001), whereas the LPO level in lung and liver increased remarkably (lung p < 0.05; liver p < 0.001). Vitamin E, C, and niacin strongly enhanced the blastogenic response of T and B splenic lymphocytes to concanavalin-A and to lipopolysaccharide (p < 0.001). The effects of methionine and B6 were much less intense. Other supplied nutrients have been shown to inhibit LPO in lung and liver of mice exposed to SiO2 (p < 0.001).

Effects of dietary supplementation on the function of alveolar macrophages of silicosis rats, on the blastogenic response of lymphocytes and on the peroxidase activity in blood of silicosis patients.

We studied the effects of a nutrient supplemented diet on the function of alveolar macrophages of silicosis rats and on the blastogenic response of lymphocytes, glutathione peroxidase (GSH-PX) activity, and lipid peroxidase (LPO) activity in the blood of silicosis patients. The results showed that a nutrient supplemented diet increased the phagocytosis rate (p < 0.01) and index (p < 0.05) of alveolar macrophages of silicosis rats. A nutrient supplemented diet also enhanced significantly the GSH-PX activity (p < 0.001) and the blastogenic response of lymphocytes (p < 0.01), and decreased substantially the LPO content (p < 0.05) in the blood of silicosis patients. We conclude that a nutrient supplemented diet may play an important role in antilipid peroxidation, decreased free radical reaction, stabilizing cell membrane, delaying lung fibrosis, and enhancing immune functions of the body.

Mapping of human chromosome 22 by in situ hybridization.

The second smallest chromosome of the human karyotype, i.e., chromosome 22, is involved in many congenital or acquired structural aberrations. This variety can be taken advantage of to determine the exact linear order, from centromere to telomere, of cloned probes and chromosomal breakpoints. Eleven probes were localized with respect to breakpoints of 11 der(22) of independent cell lines using in situ hybridization on metaphasic spreads. The deduced order of the tested probes and that of the breakpoints are in complete agreement with the published genetic map and the karyotypic analysis, respectively. This approach enables a correlation of the genetic map with the chromosomal banding.

The neuroepithelioma breakpoint on chromosome 22 is proximal to the meningioma locus.

The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids. These two probes have further been shown to be genetically linked at theta = 0.0 and a lod score of 5.3. The two probes were unaffected by a partial deletion of the chromosome 22 long arm of a meningioma, showing that the meningioma locus is distal to that of the neuroepithelioma.

Molecular characterization of different ataxia telangiectasia T-cell clones. I. A common breakpoint at the 14q11.2 band splits the T-cell receptor alpha-chain gene.

Using in situ chromosomal hybridization we have mapped the gene for the T-cell receptor alpha-chain in three different non-malignant T-cell clones occurring in ataxia telangiectasia. The constant region was translocated in each of the three clones. The variable region remained in its original position in two cases and was deleted in one clone which lost the derivative chromosome 14. We have therefore demonstrated that the T-cell receptor alpha-gene is split in at least two of these translocations. To our knowledge, this is the first direct evidence of the involvement of a gene from the immunoglobulin superfamily in chromosomal rearrangements in ataxia telangiectasia.

Establishment of a model of transplantable myelocytic leukemia (L801) in LACA mice.

A transplantable myelocytic leukemia model of LACA mice, designated by the name of L801, was established by intravenous injection of spleen cell suspension from mice with radiation-induced myelocytic leukemia into mice of the same strain. Until now, for more than three years, the L801 has maintained stable and rapid growth and has been reproduced for over 130 serial passages. The incidence of leukemia in inoculated animals was approximately 100% and mean survival time was 10.9 +/- 2.1 days. The L801 is of myelocytic type which has been determined by cytological, cytochemical, pathological and ultrastructural observations. Its karyotype was hypodiploid, characterized by modal number of 39, loss of Y chromosome and an abnormal huge marker chromosome. The cell cycle duration of the L801 was 16 h. C-type viral particles were observed under the electron-microscope. The L801 was sensitive, to varying extents, to various anti-tumor agents. We presume that the L801 is a useful tool in studies on mechanism of leukemogenesis, anti-tumor agent screening and treatment of experimental tumors.