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BACKGROUND It has been reported that paternal folic acid deficiency is correlated with male infertility and increased birth defects in the offspring. However, there are few data concerning the influence of folic acid supplementation on male-factor infertility with MTHFR gene polymorphisms. OBJECTIVES To evaluate whether folic acid supplementation has a beneficial effect on oligozoospermia with MTHFR gene polymorphisms in Chinese infertility population. MATERIALS AND METHODS The infertile men suffering oligozoospermia with MTHFR gene polymorphisms were randomly divided into the folic acid treatment groups receiving folic acid 0.8 mg daily for 3 months and the placebo groups receiving placebo for 3 months. Semen parameters, seminal MDA, and DNA fragmentation were measured. Furthermore, spontaneous pregnancy rate and live birth rate were evaluated. RESULTS Administration of folic acid for 3 months could significantly improve the seminal parameters in patients with MTHFR 677 TT genotype in comparison with that receiving placebo. Moreover, seminal MDA and sperm DNA fragmentation index in patients with MTHFR 677 TT genotype significantly declined at the end of treatment. Spontaneous pregnancy rate and live birth rate tended to be significantly higher in couples in which the men with MTHFR 677 TT genotype receiving folic acid than that receiving placebo. However, folic acid treatment did not exhibit any advantage in MTHFR 677 CT, 1298 AC, 1298 CC, 1793 GA, or combined 677 CT/1298 AC genotype. DISCUSSION The anti-oxidation function of folic acid is one of possible mechanisms invovled in improving seminal parameters and pregnancy outcome. CONCLUSIONS Folic acid supplementation has a beneficial effect on oligozoospermia with MTHFR 677 TT genotype in term of seminal parameters, seminal MDA, sperm DNA fragmentation, and pregnancy outcome.

As the endogenous ligand for the GH secretagogue receptor (GHSR), Ghrelin is aberrant expressed in multiple malignant carcinoma, and involved in regulating a number of progression of cancer, especially in metastasis and proliferation. However, the precise role of Ghrelin in tumorigenesis of gastric cancer (GC) is still poorly understood. In this study, we extensively investigated the roles and mechanisms of Ghrelin in human gastric cancer. Ghrelin levels in cancer tissues and cell lines were analyzed by immunohistochemistry, qRT-PCR, and Western blot. Functional studies were performed after Ghrelin overexpressed or knockdown in AGS cell line. Cell proliferation was evaluated in by MTT and clone formation assays. The wound healing and Transwell system were used to assess the cell migration and invasive ability of GC cells. Cell apoptosis was detected by flow cytometry, and metabolic assays were performed to reveal the function of Warburg effect in the process. Ghrelin was lowly expressed in gastric cancer tissues and cell lines. Overexpression of Ghrelin inhibited gastric cancer cell proliferation, migration, invasion, and promoted apoptosis by activating the AMPK pathway, while D-[lys3]-GHRP-6 (a GHSR agonist) treatment relieved the effect, promoting tumorigenesis. Ghrelin knockdown increased the glucose uptake and lactic acid release, suggesting that Ghrelin elicited an anti-Warburg effect via AMPK pathway to inhibit gastric tumorigenesis. Ghrelin inhibits cell proliferation, migration, and invasion by eliciting an anti-Warburg effect via AMPK signaling pathway in gastric cancer cells.

MicroRNA-34a (miR-34a) behaves as a tumor suppressor by decreasing the expression of oncogenes involved in multiple carcinogenic pathways. Intravenous delivery of miR-34a mimics has been investigated in clinical trials as a potential treatment for advanced cancers; however, the effect of miR-34a on cancer immune surveillance is controversial. In the current study, we found that miR-34a plays a dual role in the regulation of major histocompatibility complex class I-related sequence B (MICB) protein, a ligand of the NKG2D receptor. MiR-34a could both induce and reduce MICB expression by upregulating ataxia telangiectasia and Rad3-related (ATR) protein kinase and downregulating the transcription factor E2F1, respectively. The net effect of miR-34a on MICB expression depended on endogenous E2F1 levels. Overexpression of miR-34a promoted MICB expression in hepatocytes and hepatocellular carcinoma (HCC) cells that have low E2F1 levels but not in HCC cells that have high E2F1 levels. In HCC patients, the expression of miR-34a and MICB showed positive correlation in paratumor liver tissues, which have low E2F1 levels, but not in HCC tissues, which have high E2F1 levels. We showed that miR-34a overexpression in non-transformed liver cells enhanced cytolysis and interferon-γ production by NK-92MI cells. Furthermore, higher miR-34a expression in tumor and paratumor tissues was associated with positive and negative outcomes, respectively, in HCC patients. Our findings suggest that miR-34a induces MICB expression in paratumor liver tissues, which may cause liver damage and serious cytokine release syndrome, thus disclosing potential side effects of systemic administration of miR-34a in anticancer therapy.

Ghrelin is an orexigenic hormone that is produced by gastric cells. Ghrelin stimulates food intake and increases gastric movement. In rat model, injected β-hydroxybutyric acid (β-HB) leads to a decrease in body weight. It has been reported that patients with gastric erosions are slower to evacuate the stomach. The aim of the present study was to investigate the effects of ghrelin and β-HB on motility and inflammation in rat gastric antral smooth muscle cells (GASMCs). GASMCs were extracted from rat gastric antrum. Cell viability was determined using the Cell Counting Kit-8 assay. A reactive oxygen species (ROS) assay kit was used to analyze the levels of ROS using flow cytometry. Protein levels were determined using western blotting, and the expression levels of mRNAs were evaluated using reverse transcription-quantitative PCR. β-HB inhibited the expression of myosin regulatory light polypeptide 9 (MYL9), myosin light chain kinase (MLCK), transforming protein RhoA (RhoA), Rho-associated protein kinase-1 (ROCK-1) and growth hormone secretagogue receptor (GHS-R). By contrast, ghrelin increased the expression of MYL9, MLCK, RhoA, ROCK-1 and GHS-R in β-HB-treated GASMCs. β-HB increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and ROS, and decreased the levels of manganese (Mn) superoxide dismutase (SOD), copper/zinc (Cu/Zn)SOD and catalase. Ghrelin decreased the expression of TNF-α, IL-6, ROS and catalase, whereas ghrelin promoted the expression of MnSOD and Cu/ZnSOD in β-HB-treated GASMCs. Short interfering RNA targeting GHS-R inhibited the expression of MYL9, MLCK, RhoA and ROCK-1, and increased the levels of TNF-α, IL-6 and ROS in β-HB-treated or ghrelin-treated GASMCs. The present study provided preliminary evidence that β-HB inhibits the motility of GASMCs and promotes inflammation in GASMCs, whereas ghrelin decreases these effects. GHS-R acted as a primary regulator of motility and inflammation in GASMCs treated with β-HB and ghrelin.

Cucurbita species ( Cucurbita moschata and Cucurbita maxima) are rich sources of nutrients, especially carotenoids and carbohydrates. Metabolites in pulps of C. moschata and C. maxima lines were examined by high-performance liquid chromatography and gas chromatography–mass spectrometry. Our results revealed that glucose and sucrose were the dominant sugars in C. maxima and C. moschata, respectively. A correlation was found between Brix percentage and sucrose levels as compared with glucose and fructose. A greater amount of myo-inositol had accumulated in C. moschata lines compared with C. maxima. Conversely, total carotenoids and antioxidant activity were found to be higher in C. maxima lines than in C. moschata. A strong correlation of glucose, fructose, and sucrose with β-carotene and violaxanthin revealed that it will be difficult to develop pumpkin cultivars with both high inositol and carotenoid levels. In conclusion, the composition of carbohydrates and carotenoids was more diverse in C. moschata lines than in C. maxima lines. Our results will contribute to a better understanding of metabolite changes in the fruits of these as well as other pumpkin species.

The aim of this study was to investigate the role of pyroptosis in the cryopreservation and transplantation of mouse ovarian tissues; the effects of pyroptosis inhibitior on the ovarian graft function were also explored. ICR (institute of cancer research) mice were randomly divided into control group and experimental groups (n = 10 per group). The experimental groups included fresh graft group (autograft), cryopreserved graft group (cryopreservation + autograft), and pyroptosis inhibition group (cryopreservation + autograft + pyroptosis inhibitor). At the third day after auto-transplantation, caspase-1 and NLRP3 protein expression in grafts were assessed by Western blot; in the meantime, serum concentration of IL-1β was examined by ELISA. After 28 days of auto-transplantation, estradiol concentrations and follicular densities of grafts were evaluated. The caspase-1 and NLRP3 protein expression in grafts from all the experimental groups were significantly higher than that from control group respectively; moreover, there was a significant increase in serum concentrations of IL-1β in all experimental groups compared with control group. The concentration of estradiol and follicular densities of grafts in pyroptosis inhibition group were significantly higher than that in cryopreserved graft group. Pyroptosis is involved in cryopreservation and auto-transplantation of mouse ovarian tissues, and pyroptosis inhibition can improve the ovarian graft function.

Introduction:Urachal remnant with heterotopic sinus is an extremely rare congenital anomaly, and usually coexists with other congenital anomalies. We report the case of a 32-year-old adult male with urachal remnant with heterotopic sinus.Patient concerns:A 32-year-old adult male presented wi

Pathogenesis and genetic factors influencing predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) are not clear. Polymorphism at the genetic locus of a drug and xenobiotic compound metabolizing enzyme, N-acetyltransferase type 2 (NAT2), is reported to be associated with the excess generation of toxic reactive metabolites. To date, many case–control studies have been carried out to investigate the relationship between the NAT2 polymorphisms and ATDH, but the results have been inconsistent. To investigate this inconsistency, a meta-analysis was performed. Databases including PubMed, Web of Science, EMBASE and CNKI were searched to find relevant studies. A total of 26 case–control studies, involving 1,198 cases and 2,921 controls were included. Overall, we found significant association between slow acetylator genotype of NAT2 and ATDH (OR = 3.10, 95 % CI: 2.47–3.88, P < 10−5). Significant results were also found in East Asians, South Asians, Brazilians and Middle Eastern when stratified by ethnicity. However, no significant associations were found for Caucasians. This meta-analysis demonstrated that the slow acetylator genotype of NAT2 is a risk factor associated with increased ATDH susceptibility, but these associations vary in different ethnic populations.

Introduction The availability of targeted and immunotherapies has provided NSCLC patients with more effective treatment options. However, this has resulted in an increase in the number and modality of tests required for treatment selection. Given 30-50% of advanced lung cancer patients have insufficient or unavailable tissue for comprehensive genomic profiling, there is a need for a non-invasive assay that can accurately detect all guideline-recommended markers for NSCLC treatment selection. To meet this need, we have developed a blood test that detects six classes of alterations (SNV, Indels, Rearrangements, CNA, Microsatellite Instability and PD-L1 expression) for therapy selection. Methods & Results Three tubes of blood from a routine blood draw were sent to our CLIA-certified and/or CAP accredited lab for analysis. PD-L1 expression was evaluated in circulating tumor cells (CTCs) utilizing two different assays; (i) Immunofluorescence (IF) antibody staining, (ii) mRNA qPCR. CTCs were captured on the CMxTM CTC Platform coated with lipid bilayer and antibodies to EpCAM. PD-L1 expression results were highly correlated between IF and qPCR assays in ten solid tumor cell lines (lung, breast, prostate and colorectal cancer) spiked into whole blood to mimic the actual patient CTC capture process. In an ongoing study on clinical samples from NSCLC patients (N=20), we observed greater than 90% concordance between tissue (IHC by 22C3 PD-L1 clone) and blood (CTC IF and mRNA assays). A proprietary Single Molecule Sequencing (SMSEQTM) NGS assay was performed on plasma in order to detect 5 classes of genomic alterations (SNV, Indels, Rearrangements, CNA, MSI) from ctDNA. This assay was validated in accordance with the latest ACMG and AMP guidelines to accurately detect variants at low mutant allele fraction (.1% for SNVs and Indels, 1% for rearrangements and 5 copies for CNA) with high sensitivity and specificity. MSI status was determined by assessing nucleotide repeat sequences in five standard markers (BAT-25, BAT-26, MONO-27, NR-21, NR-24), and was detectable down to a MAF of 1%. In an ongoing study on clinical samples from NSCLC patients (N=20), we observed high concordance of MSI status between tissue (immunohistochemistry for dMMR/MSI status) and blood (ctDNA SMSEQ assay). Conclusion Tissue insufficiency and procurement challenges are the primary reasons why ~90% of patients diagnosed with advanced NSCLC are not comprehensively tested per NCCN-guidelines in the community setting where most cancer is treated, leading to suboptimal treatment selection. An accurate blood test that detects all 6 NCCN-recommended markers for immunotherapy and targeted therapy selection has the potential to significantly improve adherence to NCCN testing guidelines and enable optimal treatment selection. Citation Format: Huangpin B. Hsieh, Jen-chia Wu, Feng-Ming Lin, Julian Lucas, Alex Atkins, Pratyush Gupta, Hung-Jen Shao, Yen-Lin Chen, Wen-Jie Huang, Chia-Hsun Hsieh, Ruey Kuen Hsieh, Kuo-Wei Chen, Ming-Hong Yen, Mana Javey, Shih-En Chang, Twinkal Marfatia, Drew Watson, Mahul Amin, Ashish Nimgaonkar, Oscar Segurado, Rui Mei. CTC and ctDNA profiling to detect 6 NCCN-guideline recommended classes of alterations for immunotherapy and targeted therapy selection using sample from a single blood draw [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3635.

e15107Background: PD-L1 expression on circulating tumor cells (CTCs) is an alternative to checkpoint inhibitor selection by IHC and it offers possibility for serial monitoring following chemotherap...

Few studies of the efficacy and safety of therapy with combinations of salmeterol/fluticasone propionate (SFCs) have been conducted in Chinese patients with COPD, and the benefits of combination therapy in nonsmoking patients with COPD are, to our knowledge, not known.The aims were to establish the efficacy and tolerability of the therapy with SFC (salmeterol, 50 microg/fluticasone, 500 microg, twice daily) in the management of Chinese COPD patients and to investigate the effectiveness of SFC in nonsmokers with COPD.This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Changes in prebronchodilator and postbronchodilator FEV(1), quality of life determined by the St. George Respiratory Questionnaire (SGRQ) scores, relief bronchodilator use, nighttime awakenings, and frequency of exacerbations of COPD were measured in patients randomized to receive SFC (n = 297) or placebo (n = 148). Never-smokers, former smokers, and current smokers accounted for 11.7%, 66.7%, and 21.6%, respectively, of the study population.After 24 weeks, the mean changes in prebronchodilator and postbronchodilator FEV(1) were 180 mL (95% confidence interval [CI], approximately 91 to 268; p0.001) and 65 mL (95% CI, approximately 14 to 115; p = 0.012), respectively, greater for the SFC group than that for the placebo group. The differences in response to treatment were significant (all p0.0001) in former or current smokers but not in never-smokers (p0.05). The mean improvement in the total SGRQ score for the SFC group was 5.74 (p0.01) greater than that for the placebo group. SFC significantly reduced the frequency of nighttime awakenings and the use of relief bronchodilator. The adjusted ratio of exacerbations of COPD for the SFC group relative to the placebo group was 0.61 (95% CI, approximately 0.45 to 0.84; p0.01). There were no significant differences between the SFC and placebo groups in safety measures.SFC therapy achieved sustained improvement in lung function, quality of life, and control of symptoms, and was well tolerated in Chinese patients. Greater improvements in lung function were found only for COPD patients with a history of smoking.http://ctr.gsk.co.uk/Summary/fluticasone_salmeterol/studylist.asp Identifier: No. SCO100540.

The purpose of the present study was to evaluate leg muscular regulation and neuromuscular activation by investigating the stiffness and EMG amplitude between normal vision students and visually impaired students. Ten normal vision (age: 24.3 ± 2 years; 171.5 ± 4.6; mass: 65.9 ± 8.0) and 10 visually impaired students (age: 23.2 ± 2.4 years; 163.4 ± 9.6; mass: 62.8 ± 15.0) served as subjects. An AMTI force platform (1200 Hz) and a Peak Performance high speed camera (60 Hz) were used synchronously to record the ground reaction force, the kinematic parameters and EMG signals of lower extremity during the subjects stepped down from height 20, 30 and 40 cm. After treating the data and discussion, the conclusions were obtained. The regulation of neuromusclar system of the impaired is less efficient compared to the normal one because of softer stiffness and lower EMG activity.

Retrovirus has been speculated as one of the potential infectious agents involved in the development of schizophrenia. Here we used nested RT-PCR to detect the RNA of HERV pol gene in blood from schizophrenic patients and normal human. We found retroviral pol genes expressed in blood from 20 of 58 (34.5%) individuals with recent-onset schizophrenia, but not from 38 normal persons (p

Chondromas of the lung are rare benign tumors, and fewer than 100 cases with multiple chondromas have been reported since Bateson1 reported the first case. In 1977, J. Aidan Carney from the Mayo Clinic described pulmonary chondroma associated with gastrointestinal stromal tumors (GISTs) and extraadrenal paraganglioma as a syndrome, which was subsequently called the Carney triad.2 Sporadic case reports and a recent analysis demonstrated that the chondromas in the Carney triad usually occur in young women and are multiple, small, peripheral and not endobronchial, and commonly calcified.2,3 As most of the patients with Carney triad are asymptomatic and the pulmonary neoplasm(s) are usually found as incidental lesions on chest radiography, the diagnosis of Carney triad should be considered when multiple pulmonary chondromas are identified. Here, we report a case of Carney triad that initially presented with multiple lesions of the left lung.