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Background and Objectives: Genetic and dietary factors are important contributors to the development of dental fluorosis (DF). This study investigated the association between DF and dietary carotenoids, and explored whether the association was modified by polymorphisms of the antioxidant enzyme superoxide dismutase 2 (SOD2 rs11968525) in Guizhou, China.Methods and Study Design: A cross-sectional study with a total of 899 adults aged 18-75 years were enrolled in the study. Face-to-face interviews were conducted to assess dietary habits using a validated 75 item food frequency questionnaire (FFQ). Sociodemographic and lifestyle information, and blood and urine samples were also collected. Genotypes were evaluated using TaqMan single nucleotide polymorphism (SNP) Genotyping Assay.Results: There were significant dose-dependent inverse associations of the prevalence of DF with intake of α-carotene, β-carotene, lutein/zeaxanthin, lycopene and total carotenoids (p-trend ranged from <0.001-0.004). The odds ratios (ORs) and 95% confidence intervals (CIs) of DF comparing the highest against lowest quartile were 0.56 (0.35, 0.92) for α-carotene, 0.53 (0.35, 0.81) for β-carotene, 0.44 (0.27, 0.74) for lycopene, 0.35 (0.21, 0.58) for lutein/zeaxanthin in combination and 0.42 (0.25, 0.69) for total carotenoids (all p-trend<0.005). Intake of β-cryptoxanthin was not found to be related to DF. The inverse association of DF with dietary intake of α-carotene and β-carotene was more evident in individuals with the AG+AA genotype (p-interaction<0.05).Conclusions: Higher dietary carotenoids were associated with a lower occurrence of DF, polymorphisms in SOD2 (rs 11968525) modified the associations between dietary intake of carotene and DF. These findings provide evidence for precision prevention of fluorosis. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has been accompanied by promising results over the past few years. Programmed Cell Death Protein 1 (PD-1) plays a vital role in inhibiting immune responses and promoting self-tolerance through modulating the activity of T-cells, activating apoptosis of antigen-specific T cells and inhibiting apoptosis of regulatory T cells. Programmed Cell Death Ligand 1 (PD-L1) is a trans-membrane protein that is considered to be a co-inhibitory factor of the immune response, it can combine with PD-1 to reduce the proliferation of PD-1 positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 also plays an important role in various malignancies where it can attenuate the host immune response to tumor cells. Based on these perspectives, PD-1/PD-L1 axis is responsible for cancer immune escape and makes a huge effect on cancer therapy. This review is aimed to summarize the role of PD-1 and PD-L1 in cancer, looking forward to improve the therapy of cancer., Competing Interests: None., (AJCR Copyright © 2020.)

Gemcitabine and cisplatin is the first line chemotherapy for non-small cell lung cancer with high toxicity. Aidi injection is a cantharidin and astragalu-based Chinese herbs injection in China. Has Aidi injection attenuation and synergistic efficacy to GP in NSCLC? There is lack of strong evidence to prove it. To further reveal it, we systematically evaluated all related studies. We collected all studies about Aidi injection plus GP for NSCLC in Medline, Embase, Web of Science, CNKI, VIP, Wanfang Database, CBM, CCRCT, Chi-CTR, and US-clinical trials (established to June 2015). We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (5.1.0), extracted data following the PICO principles and synthesized the data by Meta analysis. Thirty six RCTs with 2582 NSCLC patients were included, with general methodological quality in most trials. The RR values and their 95% CI of Meta-analysis for ORR, DCR and QOL were as following: 1.28 (1.17, 1.39), 1.11(1.07, 1.15) and 1.81 (1.61, 2.03). The merged RD values and their 95% CI of Meta-analysis for myelosuppression, neutropenia, thrombocytopenia, neurotoxicity and nausea and vomiting were as following: -0.23(-0.29, -0.17), -0.17(-0.22, -0.11), -0.13(-0.18, -0.08), -0.06(-0.17, 0.05) and -0.15(-0.21, -0.10). To compare with GP alone, all differences were statistically significant. The available evidence indicates that Aidi injection plus GP can significantly increase the clinical efficacy and improve the QOL of patients with NSCLC. Aidi injection can reduce myelosuppression, neutropenia, thrombocytopenia neurotoxicity and nausea/vomiting. These indirectly reveal that Aidi injection has the attenuation and synergistic efficacy to GP chemotherapy in NSCLC.

Epidermal growth factor receptor (EGFR) expression and gene copy number have been observed to be associated with a positive clinical response to EGFR inhibitors. The present study aimed to evaluate EGFR expression and gene copy number in samples of gastric carcinoma (GC) from Chinese patients. EGFR expression and gene copy number were detected using immunohistochemistry and fluorescence in situ hybridization, in tissue array slides containing 150 individual samples of GC tissue. The association between EGFR status, clinicopathological features and overall patient survival was analyzed. Out of the 150 cases of GC evaluated, 63 (42.00%) demonstrated weak EGFR expression and 20 (13.33%) demonstrated EGFR overexpression. EGFR expression was observed to be associated with tumor location (P<0.05). Out of 104 cases of GC, which produced a clear FISH signal, 6 (5.77%) exhibited EGFR gene amplification and 5 (4.80%) exhibited balanced polysomy. Patients exhibiting GC, who demonstrated weak EGFR expression, EGFR overexpression or increased EGFR gene copy number, possessed an unfavorable prognosis. Multivariate analysis revealed that EGFR expression, tumor/node/metastasis stage and tumor location were potential independent unfavorable prognostic factors for GC patients. In conclusion, EGFR overexpression, gene amplification and polysomy were observed in GC patients and were associated with an unfavorable prognosis. Evaluation of EGFR status may therefore facilitate the identification of a subset of GC patients sensitive to treatment with EGFR-targeted therapies.

Objective: To develop psychosocial adaptation scale for Parkinson's disease (PD) in Chinese population and evaluate its reliability and validity., Methods: The items were designed by literature review, expert consultation and semi-structured interview. The methods of corrected item-total correlation, discrimination analysis and exploratory factor analysis were used for items selection. 427 valid scales from PD patients were collected in the study to test the reliability and validity., Results: The scale incorporated six dimensions: anxiety, self-esteem, attitude, self-acceptance, self-efficacy and social support, a total of 32 items. The scale possessed good internal consistency. The test-retest correlation coefficient was 0.99 and average content validation rate was 0.97. The Hoehn and Yahr stage were correlated with total score of the scale., Conclusions: The psychosocial adaptation scale in this study showed good reliability and validity, it can be used as a reliable and valid instrument to evaluate the psychosocial adaptation of PD objectively and effectively.

Objective: To investigate the inhibitory effect of salinomycin on human breast cancer cells in vitro, and to explore the related molecular mechanism., Methods: Human breast cancer MDA-MB-231 cells were treated with salinomycin at different concentrations and at various time points. The effect of salinomycin on MDA-MB-231 cells proliferation was studied by CCK-8 method. The cell cycle status was examined by flow cytometry. RT-PCR and Western blot were used to detect the expression of Shh, Smo and Gli1 in the Hedgehog pathway at mRNA and protein levels., Results: Proliferation of MDA-MB-231 cells treated with salinomycin was markedly inhibited in a concentration and time dependent manner. Salinomycin at concentrations of 0, 0.4, 0.8 and 1.6 µmol/L inhibited the growth at the rates of 11.18%, 25.88%, 50.03%, 92.65%, respectively. Salinomycin prevented MDA-MB-231 cells from G1 into S phase. Salinomycin at concentrations of 0, 0.8 and 1.6 µmol/L resulted in S-phase percentage of 25.03%, 11.85% and 35.21%, respectively (P < 0.05). RT-PCR and Western blot showed that the expression of key elements Shh, Smo and Gli1 in the Hedgehog pathway was inhibited by salinomycin in a concentration dependent manner (P < 0.05)., Conclusion: Salinomycin prevents breast cancer cell transition from G1 to S phase through downregulation of the target genes of Hedgehog signaling pathway, leading to an effective inhibition of MDA-MB-231 cells.

Objective: To investigate the effect of microRNA-140 (miR-140) on the migration and invasion of colorectal cancer (CRC) cells and the possible mechanism., Methods: miR-140 mimics, miR-140 specific inhibitor or small interfering RNA (siRNA) against Smad3 were transfected into human CRC cell line RKO cells respectively, using Oligofectamine or Lipofectamine2000. Quantitative real-time PCR (real-time PCR) was used to measure the expression levels of miR-140 and Smad3 mRNA. Smad3 protein was analyzed by Western blot. The in vitro cell migrating and invasive abilities were determined by wound-healing and Transwell chamber assay after up-regulating or down-regulating miR-140 or knocking down Smad3., Results: The Western blot assays showed that the Smad3 protein level was significantly reduced after up-regulating miR-140 (0.04 ± 0.01), compared with that of (0.47 ± 0.02, P < 0.05) in the control group and that of (0.52 ± 0.06) in the negative control group (P < 0.05 for both). The results of real-time PCR indicated that no significant difference was found in the levels of Smad3 mRNA between miR-140 transfection and NC groups (1.11 ± 0.13 vs. 1.00 ± 0.06, P > 0.05). The wound-healing assay showed that the migrating ability was dramatically attenuated by miR-140 compared with that in the control and NC groups, whereas no significance was found when compared with that of the Smad3 siRNA transfected cells. The number of cells migrating through Transwell chamber without matrigel in the miR-140 group was (76.2 ± 4.4), remarkably lowered than that in the control (267.1 ± 4.9) and NC (336.1 ± 5.7) groups (P < 0.05 for both), but no significant difference between the miR-140 (76.2 ± 4.4) and Smad3 siRNA (83.5 ± 7.3) groups. Transwell chamber with matrigel assay showed that number of cells penetrating through the membrane was (109.5 ± 7.4) in the miR-140 group, significantly lower than that in the control (403.1 ± 5.1) and NC (392.6 ± 8.4) groups (P < 0.05 for both), while Smad3 siRNA transfection had a similar effect (138.8 ± 3.6)(P > 0.05). Down-regulation of miR-140 increased the level of smad3 protein expression, and partially reversed the inhibition of the cell migration and invasion mediated by miR-140. Co-transfection of miR-140 inhibitor and Smad3 siRNA had no significant effect on the Smad3 protein expression and the abilities of cell migration and invasion., Conclusions: miR-140 regulates the Smad3 expression at the post-transcriptional level. miR-140 suppresses the migrating and invasive abilities of CRC cells, possibly through down-regulation of Smad3. The findings of this study suggest that miR-140 may have a unique potential as a possible biomarker candidate for diagnosis and therapy of tumor metastasis.

Objective: Chlorhexidine gluconate (CHG) is a common and safe antimicrobial agent and has been used widely in hand hygiene and skin disinfection; however, whether daily bathing with CHG results in the reduced acquired infection of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) remains inconclusive., Methods: We did a meta-analysis searching PubMed, Embase and the Cochrane Central Register database for available studies. Primary outcomes were acquired infection of MRSA, VRE., Results: In all, twelve articles were available in this review. We found that daily application of chlorhexidine bathing would significantly low the acquired colonization of MRSA [incidence rate ratio (IRR) =0.58, 95% confidence interval (CI): 0.41-0.82] or VRE (IRR =0.51, 95% CI: 0.36-0.73). Remarkably, the using of CHG bathing would significantly reduce the MRSA infection (IRR =0.56, 95% CI: 0.37-0.85), MRSA ventilator associated pneumonia (VAP) (IRR =0.22, 95% CI: 0.07-0.64) and VRE infection (IRR =0.57, 95% CI: 0.33-0.97). No significant publication bias was found in this meta-analysis., Conclusions: The application of CHG bathing would significantly decrease acquired infection of MRSA or VRE, which may be an important complementary intervention to barrier precautions.

The purpose of this study was to investigate the activation of Hedgehog (Hh) signaling molecules and its involvement in triple-negative breast cancer (TNBC). A total of 123 cases of paraffin blocks, including 83 cases of primary breast carcinoma, 30 cases of mammary hyperplasia and 10 cases of normal breast tissue, were immunohistochemically analyzed for Sonic Hedgehog (SHH), Patched-1 (PTCH1), Smoothened (SMO) and glioma-associated oncogene homoglog 1 (GLI1) expression. The expression of SMO and GLI1 in TNBC was significantly increased in comparison to non-triple-negative breast cancer (nTNBC). GLI1 expression manifested an inverse association with the estrogen receptor. The levels of GLI1 expression were increased in lymph node-positive cases. The expression of SHH and SMO was increased in high histological grades. Furthermore, the expression of SMO and GLI1 was correlated with superior tumor stage. The expression of SHH, SMO and GLI1 was significantly increased in breast cancer and mammary hyperplasia. PTCH1 expression was significantly decreased in breast cancer compared to mammary hyperplasia and normal breast tissue. For the first time, clinical evidence has been provided in support of significant roles of Hh signaling in TNBC. Hh signaling is involved in breast ductal changes and malignant transformation. Measures to inhibit Hh activity may improve the prognosis of TNBC patients.