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BACKGROUND: Multivitamins are among the most commonly used supplements in the United States, but their effectiveness in preventing cancer remains unclear. OBJECTIVES: We prospectively examined the association between multivitamin use and risks of overall and site-specific cancer in a large, well-characterized cohort to ascertain potential preventive or harmful relationships. METHODS: We examined 489,640 participants ages 50–71 in the NIH–American Association of Retired Persons (AARP) Diet and Health Study who were enrolled from 1995 to 1998. We linked to 11 state cancer registries in order to identify incident cancers. Multivitamin use was assessed by a baseline questionnaire. Cox proportional hazards regression models of multivitamin use were used to estimate HRs and 95% CIs for cancer risks in men and women, adjusted for potential confounders, including age, BMI, smoking, physical activity, the Healthy Eating Index 2015 score, and use of single-vitamin/-mineral supplements. RESULTS: A slightly higher overall cancer risk was observed in men (but not women) who consumed 1 or more multivitamins daily compared to nonusers [HRs, 1.02 (95% CI: 1.01–1.04) and 1.03 (95% CI: 1.00–1.07), respectively; P-trend = 0.002]. The latter reflected higher risks for prostate cancer (HR, 1.04; 95% CI: 0.98–1.10; P-trend = 0.005), lung cancer (HR, 1.07; 95% CI: 0.96–1.20; P-trend = 0.003), and leukemia (HR, 1.26; 95% CI: 1.02–1.57; P-trend = 0.003). Taking more than 1 multivitamin daily was also strongly positively associated with the risk of oropharyngeal cancer in women (HR, 1.53, 95% CI: 1.04–2.24; P-trend

Deep learning for ultrasound image formation is rapidly garnering research support and attention, quickly rising as the latest frontier in ultrasound image formation, with much promise to balance both image quality and display speed. Despite this promise, one challenge with identifying optimal solutions is the absence of unified evaluation methods and datasets that are not specific to a single research group. This article introduces the largest known international database of ultrasound channel data and describes the associated evaluation methods that were initially developed for the challenge on ultrasound beamforming with deep learning (CUBDL), which was offered as a component of the 2020 IEEE International Ultrasonics Symposium. We summarize the challenge results and present qualitative and quantitative assessments using both the initially closed CUBDL evaluation test dataset (which was crowd-sourced from multiple groups around the world) and additional in vivo breast ultrasound data contributed after the challenge was completed. As an example quantitative assessment, single plane wave images from the CUBDL Task 1 dataset produced a mean generalized contrast-to-noise ratio (gCNR) of 0.67 and a mean lateral resolution of 0.42 mm when formed with delay-and-sum beamforming, compared with a mean gCNR as high as 0.81 and a mean lateral resolution as low as 0.32 mm when formed with networks submitted by the challenge winners. We also describe contributed CUBDL data that may be used for training of future networks. The compiled database includes a total of 576 image acquisition sequences. We additionally introduce a neural-network-based global sound speed estimator implementation that was necessary to fairly evaluate the results obtained with this international database. The integration of CUBDL evaluation methods, evaluation code, network weights from the challenge winners, and all datasets described herein are publicly available (visit https://cubdl.jhu.edu for details).

Background According to the International Agency for Research on Cancer, some hair dye chemicals are considered mutagenic and carcinogenic in humans. One hospital-based study reported a positive association between hair dye use and prostate cancer risk, but no prospective analyses have been conducted. Methods This study investigated the association between hair dye use and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort, a large, well-characterized cohort of 29,133 male Finnish smokers. Participants completed questionnaires regarding lifestyle, medical, and risk factor information, including the use of hair dye, which was available for 98.8% of the cohort (28,795 men). Prostate cancer cases were identified through linkage with the Finnish Cancer Registry and the Finnish Mortality Register. Hazard ratios (HRs) and confidence intervals (CIs) were estimated via multivariable Cox proportional hazards regression. Results During a 28-year period of observation, 2703 incident prostate cancer cases were diagnosed. As reported at the baseline, 75 men used hair dye, and 13 of these men were subsequently diagnosed with prostate cancer. After adjustments for potential confounders, men who used hair dyes experienced substantially higher prostate cancer risk than men who did not (HR, 1.77; 95% CI, 1.03-3.05). Conclusions This first prospective investigation of hair dye use and prostate cancer suggests that personal hair dye use may be related to increased risk. The findings warrant re-examination in other prospective cohorts along with studies evaluating specific hair dyes and possible underlying biological mechanisms.

How retinol as a clinical indicator of vitamin A status is related to long-term mortality is unknown. Here we report the results of a prospective analysis examining associations between serum retinol and risk of overall and cause-specific mortality. During a 30-year cohort follow-up, 23,797 deaths were identified among 29,104 men. Participants with higher serum retinol experienced significantly lower overall, CVD, heart disease, and respiratory disease mortality compared to men with the lowest retinol concentrations, reflecting 17–32% lower mortality risk (Ptrend, Vitamin A, of which retinol is the major form in the circulation, is a determinant of human health but whether vitamin A status is associated with mortality is not well understood. Here the authors report that in a prospective observational analysis of 29 104 men, higher serum retinol associates with lower risk of overall and cause-specific mortality.

Gardenia blue is a natural blue pigment that is environmentally friendly, non-toxic, and stable. The hydrolysis of geniposide, catalyzed by β-glucosidase, is a critical step in the production process of gardenia blue. However, β-glucosidase is not resistant to high temperatures, limiting the production of gardenia blue. In this study, we investigated the effectiveness of a heat-resistant glucosidase obtained from Thermotoga maritima in the production of gardenia blue. The enzyme exhibited a maximum activity of 10.60 U/mL at 90 °C. Single-factor and orthogonal analyses showed that exogenously expressed heat-resistant glucosidase reacted with 470.3 μg/mL geniposide and 13.5 μg/mL glycine at 94.2 °C, producing a maximum yield of 26.2857 μg/mL of gardenia blue after 156.6 min. When applied to the dyeing of denim, gardenia blue produced by this method yielded excellent results; the best color-fastness was achieved when an iron ion mordant was used. This study revealed the feasibility and application potential of microbial production of gardenia blue.

Objective To evaluate the effect of probiotics on gingival inflammation and oral microbiota in patients suffering from plaque-induced gingivitis. Methods PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE were electronically searched until December 2020. The quality of included studies was assessed with the Cochrane Collaboration's Risk of Bias tool. The differences were expressed as weighted mean differences (WMD) and 95% of confidence interval (95% CI). I2 test was performed to evaluate the heterogeneity of the studies. All analyses were performed using Review Manager (version 5.3). Results Eleven randomized and controlled trials were included, enrolling 554 patients. All comparisons displayed that oral probiotics had no significant improvement in the Gingival index (GI), Plaque index (PI), and Bleeding on probing (BOP) of patients with plaque-induced gingivitis. In terms of microecology, no significant difference in the volumes of Gingival crevicular fluid (GCF), the concentration of IL-1β and the counts of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi) and Fusobacterium nucleatum (Fn) were found between the probiotic group and the placebo group. Conclusion There exists no clear evidence that oral probiotics has positive effect on the gingival inflammation and oral microecological environment of patients with plaque-induced gingivitis.

Background During outbreak of Coronavirus Disease 2019 (COVID-19), healthcare providers are facing critical clinical decisions based on the prognosis of patients. Decision support tools of risk stratification are needed to predict outcomes in patients with different clinical types of COVID-19. Methods This retrospective cohort study recruited 2425 patients with moderate or severe COVID-19. A logistic regression model was used to select and estimate the factors independently associated with outcomes. Simplified risk stratification score systems were constructed to predict outcomes in moderate and severe patients with COVID-19, and their performances were evaluated by discrimination and calibration. Results We constructed two risk stratification score systems, named as STPCAL (including significant factors in the prediction model: number of clinical symptoms, the maximum body temperature during hospitalization, platelet count, C-reactive protein, albumin and lactate dehydrogenase) and TRPNCLP (including maximum body temperature during hospitalization, history of respiratory diseases, platelet count, neutrophil-to-lymphocyte ratio, creatinine, lactate dehydrogenase, and prothrombin time), to predict hospitalization duration for moderate patients and disease progression for severe patients, respectively. According to STPCAL score, moderate patients were classified into three risk categories for a longer hospital duration: low (Score 0–1, median = 8 days, with less than 20.0% probabilities), intermediate (Score 2–6, median = 13 days, with 30.0–78.9% probabilities), high (Score 7–9, median = 19 days, with more than 86.5% probabilities). Severe patients were stratified into three risk categories for disease progression: low risk (Score 0–5, with less than 12.7% probabilities), intermediate risk (Score 6–11, with 18.6–69.1% probabilities), and high risk (Score 12–16, with more than 77.9% probabilities) by TRPNCLP score. The two risk scores performed well with good discrimination and calibration. Conclusions Two easy-to-use risk stratification score systems were built to predict the outcomes in COVID-19 patients with different clinical types. Identifying high risk patients with longer stay or poor prognosis could assist healthcare providers in triaging patients when allocating limited healthcare during COVID-19 outbreak.

Currently, biodiesel has been received much attention from many researchers around the world due to its clean and renewable characteristics. In the present study, combustion and emissions characteristics have been studied on a modified four-cylinder, 4-stroke, water-cooled, direct injection compression internal engine equipped with a common rail fuel injection system fueled with methanol-biodiesel blends as well as pure biodiesel. The experiment was operated at a constant engine speed of 1800 rpm and injection timing from 2.5-22.5 ? crank angle before top dead center. With the injection timing advanced, peak in-cylinder pressure and maximum heat release rate increased while combustion start points were advanced. Ignition delay was shorten first and then prolonged while brake thermal efficiency was increased first and then decreased. With the injection timing in advance, NOx emissions increased, 1,3-butadiene and benzene emissions decreased while hydrocarbon and acetaldehyde emissions decreased first and then increased, and soot emissions increased first and then decreased.

Objective The prevalence of childhood asthma has been increasing in recent years. This study aims to investigate the involvement of the key molecules of IL-1 (interleukin-1) signaling pathways in pediatric patients with asthma. Methods Differentially expressed genes (DEGs) associated with IL-1 signaling pathways were identified with RNA-seq from peripheral blood samples collected from asthmatic or healthy children and were further verified in clinical peripheral blood samples. Cellular models and asthmatic mice were subsequently developed to validate the identified asthmatic markers. Results Among the DEGs identified by RNA-seq, eight signal transducers associated with the IL-1 signaling network, namely IL-1RN, IL-1β, IL-1RAP, IRAK3, IL-1R1, MYD88, IRAK2 and PELI1, were found to be substantially upregulated in children with asthma. Interestingly, a significant serially increased expression of four genes (IL-1RN, IL-1RAP, IRAK3 and PELI1) were observed in healthy subjects, patients with chronic persistent asthma and patients with acute exacerbation asthma. In particular, these four genes were continuously overexpressed in recurrent patients. A significant induction of the above four genes was then observed in house dust mite (HDM)-stimulated peripheral blood mononuclear cells (PBMCs) and ovalbumin (OVA)-induced asthmatic mice. In addition, a time-dependent induction of IL-1RAP and PELI1 was also detected in HDM-treated THP-1 cells, an acute monocytic leukemia cell line. Conclusions These results demonstrate that IL-1RN, IL-1RAP, IRAK3 and PELI1, which are signal transducers of the IL-1 signaling pathway, could serve as biomarkers for the pathogenesis of childhood asthma and for potential therapeutic targets of asthma.

Background Patients with atrial fibrillation are at increased risk of stroke and mortality. It is not clear if inflammatory biomarkers are associated with stroke and mortality in patients with atrial fibrillation. We aimed to evaluate the predictive value of three inflammatory biomarkers (interleukin [IL]-9, IL-10, and interferon [IFN]-γ) for stroke and mortality in atrial fibrillation. Method A total of 232 patients with new-onset atrial fibrillation were enrolled and 217 patients were completely followed-up. Peripheral plasma concentrations of cytokines (IL-9, IL-10, and IFN-γ) were measured using Luminex xMAP assays. The association between dichotomous groups of cytokines and outcomes were evaluated by a Cox proportional hazards model. The incremental value of inflammatory biomarkers, in addition to the CHA2DS2-VASc score, was also assessed. Results Patients were followed-up for a median duration of 27 (interquartile range [IQR], 23-30) months. The elevated plasma level of IFN-γ was an independent risk factor for stroke (hazard ratio [HR], 4.02 [IQR, 1.06-15.34]; p=0.042) and all-cause mortality (HR, 3.93 [IQR, 1.43-10.78]; p=0.008) in patients with atrial fibrillation. Adding high IFN-γ to the CHA2DS2-VASc score showed improvement in discrimination and reclassification prediction for stroke and mortality. However, IL-9 and IL-10 had no statistically significant association with stroke and all-cause mortality in patients with atrial fibrillation. Conclusions In this “real-world” cohort of patients with atrial fibrillation, we have shown for the first time that plasma levels of IFN-γ could provide incremental prognostic value supplementary to that obtained from the CHA2DS2-VASc scores for predicting of stroke and all-cause mortality.

Background: Vitamin E is an essential micronutrient and critical human antioxidant previously tested for cancer preventative effects with conflicting clinical trial results that have yet to be explained biologically. Methods: We examined baseline and on-trial serum samples for 154 men randomly assigned to receive 400 IU vitamin E (as alpha-tocopheryl acetate; ATA) or placebo daily in the Vitamin E Atherosclerosis Prevention Study (VEAPS), and for 100 men administered 50 IU ATA or placebo daily in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC). Over 970 metabolites were identified using ultrahigh-performance LC/MS-MS. Linear regression models estimated the change in serum metabolites of men supplemented with vitamin E versus those receiving placebo in VEAPS as compared with ATBC. Results: Serum alpha-carboxyethyl hydrochroman (CEHC) sulfate, alpha-tocopherol, and beta/gamma-tocopherol were significantly altered by ATA supplementation in both trials (all P values ≤5.1 × 10−5, the Bonferroni multiple comparisons corrected statistical threshold). Serum C22 lactone sulfate was significantly decreased in response to the high-dose vitamin E in VEAPS (β = −0.70, P = 8.1 × 10−6), but not altered by the low dose in ATBC (β = −0.17, P = 0.4). In addition, changes in androgenic steroid metabolites were strongly correlated with the vitamin E supplement–associated change in C22 lactone sulfate only in the VEAPS trial. Conclusions: We found evidence of a dose-dependent vitamin E supplementation effect on a novel C22 lactone sulfate compound that was correlated with several androgenic steroids. Impact: Our data add information on a differential hormonal response based on vitamin E dose that could have direct relevance to opposing prostate cancer incidence results from previous large controlled trials.

The nicotinamide adenine dinucleotide (NAD+ )/Sirtuin (SIRT) system is linked to metabolic adaptation. This study aimed to determine the temporal profile of metabolic responses of the liver to cold exposure and changes in the hepatic NAD+ /SIRT system. Eight-week-old male C57BL/6 mice were individually housed in conventional cages under cold exposure (4 °C) for up to 5 days. Cold exposure decreased the hepatic triglyceride level and cholesterol level in mice by 1.7- and 1.6-fold, respectively. Lipogenic gene expression was persistently reduced, while gluconeogenic gene expression was transiently increased. Hepatic NAD+ /SIRT metabolism was induced during the 'cold remodeling' phase (days 1-3) and correlated with decreasing lipogenic and increasing gluconeogenic gene expression, contributing to the maintenance of whole-body lipid and glucose homeostasis.

Accumulated extracellular adenosine suppresses antitumor immunity via adenosine 2A receptor (A2AR). Blockade of A2AR with DZD2269 can inhibit phosphorylation of cAMP response element-binding protein mediated by adenosine analogue in vitro and in vivo. Irradiation can cause the release of adenosine and lead to a rapid increase in free extracellular adenosine in the tumour area. DZD2269, a novel A2AR Antagonism, induces incomplete antitumor responses in multiple syngeneic mouse tumour models. Combining DZD2269 with IR can induce a synergistic anticancer effect. IR increases the infiltration of various subtypes of T cells, including CD4+, CD8+ and Foxp3+ T cells, into the tumour area. Combining IR and DZD2269 improves the tumour immune microenvironment, leading to suppressed infiltration of regulatory T (Treg) cells and enhanced IFN-γ expression by tumour-infiltrating lymphocytes. The results support the use of A2AR antagonism with DZD2269 as a therapeutic strategy for monotherapy or combination therapy with IR.

Background Radical prostatectomy (RP) is the primary treatment of localized prostate cancer. Immediate urinary incontinence post-RP was still common and depressing without specific reason. Methods A multicenter cohort of 154 consecutive patients from 2018 to 2020, who was diagnosed with localized prostate cancer underwent either modified mini-incision retropubic radical prostatectomy (Mmi-RRP) or laparoscopic radical prostatectomy (LRP) or robotic-assisted radical prostatectomy (RARP). Seventy-two patients with Denonvilliers’ fascia (DF) spared were included in DFS (Denonvilliers’ fascia sparing) group. Whereas eighty-two patients with DF completely or partially dissected were set as Group Control. The primary outcome was immediate continence (ImC). Continuous data and categorical data were analyzed with t-test and Chi-square test, respectively. Odds ratios (ORs) were calculated with logistic regression. Results Urinary continence of Group DFS was significantly better than that of Group Control at each time point within one year after operation. Incidence rate of continence in Group DFS and Group Control were 83.3% vs 13.4% (P P P P = 0.02) at 1 year after operation, respectively. Positive surgical margin (PSM) showed no significant difference (20.8% vs 20.7%, P = 1.0). In multivariate analysis, DFS showed importance for ImC post RP (OR = 26.4, P Conclusions Denonvilliers’ fascia acted as the fulcrum and hammock for continence post RP. Preservation of DF contributed to better continence after RP without increase of PSM. Trail registration Our research was conducted retrospectively and approved by the ethical committees of Minhang Hospital, but not registered.

Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.

The Assessment andAppraisal Method for Ecological Construction Targets (the Method) was promulgated in 2016, which provided a concrete instruction for China’s air pollution control and established an explicit standard for reducing air pollutant concentration. This study implements a sharp regression discontinuity (RD) design and makes an assessment on air quality control effectiveness of the Method based on the high-volume big data acquired from 173 cities in China. The results show that the Method has significantly improved air pollution control on the overall air quality index (AQI) and reducing concentrations of PM2.5, PM10, SO2, NO2, and CO across the country in the observation periods. However, no reduction effect was observed for O3. The robustness tests support the conclusion as well. Besides, the heterogeneity analysis illustrates that the policy had a significant short-term treatment effect in East, South, Central, North, Northwest, Southwest, and Northeast China. However, the Method’s effect is found to decline over time either nationwide or regionally according to the persistence analysis. Therefore, this article puts forward several suggestions regarding the formulation of long-term regulations for air pollution control, the transformation of the growth model for sustainable development, and optimization of the incentive system for improved pollution control and prevention.

BackgroundBacterial proliferation on the endosseous implants surface presents a new threat to the using of the bone implants. Unfortunately, there is no effective constructed antibacterial coating which is bacterial anti-adhesion substrate-independent or have long-term biofilm inhibition functions.MethodsDrug release effect was tested in Chymotrypsin (CMS) solution andS. aureus. We used bacterial inhibition rate assays and protein leakage experiment to analyze the in vitro antibacterial effect of (Montmorillonite/Poly-l-lysine-Chlorhexidine)10[(MMT/PLL-CHX)10] multilayer film. We used the CCK-8 assay to analyze the effect of (MMT/PLL-CHX)10multilayer films on the growth and proliferation of rat osteoblasts. Rat orthopaedic implant-related infections model was constructed to test the antimicrobial activity effect of (MMT/PLL-CHX)10multilayer films in vivo.ResultsIn this study, the (MMT/PLL-CHX)10multilayer films structure were progressively degraded and showed well concentration-dependent degradation characteristics following incubation withStaphylococcus aureusand CMS solution. Bacterial inhibition rate assays and protein leakage experiment showed high levels of bactericidal activity. While the CCK-8 analysis proved that the (MMT/PLL-CHX)10multilayer films possess perfect biocompatibility. It is somewhat encouraging that in the in vivo antibacterial tests, the K-wires coated with (MMT/PLL-CHX)10multilayer films showed lower infections incidence and inflammation than the unmodified group, and all parameters are close to SHAM group.Conclusion(MMT/PLL-CHX)10multilayer films provides a potential therapeutic method for orthopaedic implant-related infections.

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2), which regulates downstream gene expression by trimethylation of lysine 27 in histone H3 (H3K27me3). EZH2 mutations or overexpressions are associated with many types of cancer. As inhibition of EZH2 activity could upregulate the expression of tumor suppressor genes, EZH2 has recently become an interesting therapeutic target for cancer therapy. Moreover, accumulating evidence has shown that EZH2 may contribute to the regulation of immune cells, especially T cells. EZH2 regulates T cell development, differentiation, and function, suggesting that EZH2 also regulates immune homeostasis in addition to tumor suppressor genes. Moreover, EZH2 can regulate T cell fate by targeting non-T cell factors such as metabolism, cytokines, and myeloid-derived suppressor cells. The role of EZH2 in this process has not been fully addressed. This review discusses up-to-date research on EZH2-mediated regulation of immunological function and the progress of immunological therapeutic strategies based on this regulation.

Patients with persistent sciatic artery are at high risk for development of limb ischemia, aneurysm formation, and embolism. In this report, we identify a nonclassified left leg persistent sciatic artery in a patient with chronic limb ischemia. Vascular reconstruction was carried out by common iliac-deep femoral artery bypass to restore adequate arterial flow. Our approach to placement of the distal anastomosis on the deep femoral artery instead of on the popliteal artery, which is used in routine practice, may potentially increase treatment efficacy and decrease surgical complications. At 2-year follow-up, the patient remained asymptomatic and in good health. Keywords: Persistent sciatic artery (PSA), Bypass, Patency

Objective: Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation. Methods: We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotype–phenotype correlation analysis. Results: The A allele of rs4468255 was significantly associated with IDCM (P

Rationale: Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and long-term mortality has not been conducted. Objective: Determine whether serum α-tocopherol (the predominant form of vitamin E) is related to long-term overall and cause-specific mortality and elucidate the dose-response relationships with better quantification of the associations. Methods and Results: We conducted a biochemical analysis of 29 092 participants in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) that originally tested vitamin E and β-carotene supplementation. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and during a 30-year follow-up we identified 23 787 deaths, including deaths from cardiovascular disease (9867), cancer (7687), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2698). After adjusting for major risk factors, we found that men with higher serum α-tocopherol had significantly lower all-cause mortality (hazard ratios=0.83, 0.79, 0.75, and 0.78 for quintile 2 (Q2)–Q5 versus Q1, respectively; P trend P interaction ≤0.006). Conclusions: In this long-term prospective cohort study, higher baseline serum α-tocopherol biochemical status was associated with lower risk of overall mortality and mortality from all major causes. Our data support the long-term health benefits of higher serum α-tocopherol for overall and chronic disease mortality and should be replicated in other more diverse populations.

Ovarian cancer is the deadliest gynecologic malignancy, which poses a great threat to female health. Anti-angiogenic therapy could bring clinical benefit for patients with ovarian cancer. Apatinib, an oral small-molecule vascular endothelial growth factor receptor-2 inhibitor, has shown notable therapeutic effect in a wide variety of tumors. We report a woman with advanced ovarian cancer who received apatinib at 250 mg/day after failure of multiple-line treatment regimens, followed by discussion through review of literature. The patient has quite a long progression-free survival time of 24 months, with a satisfactory quality of life. Apatinib monotherapy may provide an additional option for advanced ovarian cancer，but it still needs further observation and exploration.

Aims The present study was designed to study changes and its potential mechanisms in human bladder smooth muscle subjected to stretch. Methods Bioinformatics analyses including differential expression analysis, overrepresentation enrichment analysis, principal component analysis, and weighted gene coexpression network analysis were used to analyze a microarray dataset (GSE47080) of partial bladder outlet obstruction (pBOO) in rat to find the potential changes of gene expressions. Bladder from pBOO model and human bladder smooth muscle cells (HBSMCs) subjected to sustained prolonged stretch were collected for Western blot analysis, real-time polymerase chain reaction, and fluorescence analysis to verify the changes of gene expressions and preliminarily study the potential role of signaling pathway regulation in treatment of pBOO. Results The bioinformatics analysis showed that chronic obstruction activated mitogen-activated protein kinase pathway and changed cytoskeleton structure in bladder smooth muscle. In in vivo experiments in mice, pBOO was verified by cystometry. Partial BOO activated the extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 protein kinase (p90RSK)/nuclear factor-κB (NF-κB) signaling pathway in DM. The messenger RNA (mRNA) expressions of contractile phenotypic proteins increased after pBOO. In in vitro experiments of HBSMCs, mechanical stretch activated ERK/p90RSK/NF-κB in HBSMCs in a time-dependent manner. The mRNA expressions of α-smooth muscle actin and SM22 also increased and filamentous actin (F-actin) polymerization was enhanced as well. Inhibition of ERK/p90RSK/NF-κB pathway reversed mechanical stretch-induced changes of contractile phenotypic expression and F-action polymerization. Conclusions Continuous stretch increases expressions of contractile phenotypic proteins and promotes the polymerization of F-actin. This process partially goes through ERK/p90RSK/NF-κB pathway.

Cisplatin (CDDP) and arsenic trioxide (ATO), two representative inorganic anticancer drugs, have been successful in the treatment against several kinds of malignancies. However, combination therapy with these two drugs in clinical application suffers from poor pharmacokinetics, serious side effects, and drug resistance of the tumor. Herein, we report a carrier-free aquo-cisplatin arsenite multidrug nanocomposite loaded with cisplatin and arsenic trioxide prodrugs simultaneously. This nanocomposite achieves a high loading capacity and pH-dependent controlled release of the drugs. Because of these features, this nanocomposite shows better in vitro toxicity against various carcinoma cell lines than either the single drug or free drug combination, promotes the synergistic effect of cisplatin and arsenic trioxide, and significantly inhibits the growth of tumors in vivo. Furthermore, cisplatin and arsenic trioxide in this nanocomposite can realize a coordination of both enhanced DNA damage and DNA repair interference within cisplatin-resistant cells, which results in overcoming the drug resistance effectively. Gene expression profiles demonstrate the reduced expression of proto-oncogenes and DNA damage repair related genes MYC, MET, and MSH2, along with the increase of tumor suppressor genes PTEN, VHL, and FAS after the nanocomposite treatment. This type of multidrug nanocomposite offers an alternative and promising strategy for combination therapy and overcoming drug resistance.

BACKGROUND Lin28 is a gene involved in many biological processes, including development, glucose metabolism, and tumorigenesis. Let-7 miRNA is a tumor-suppressor gene that is frequently inactivated in cancer cells. The role of c-Myc (a target gene of let-7) and the Lin28-let-7-c-Myc pathway in the growth and malignancy of thyroid cancer is unclear. The purpose of the present study was to evaluate the expression of Lin28A, let-7a, and c-Myc in human papillary thyroid carcinoma (PTC) and to investigate their potential mechanisms in the progression of PTC. MATERIAL AND METHODS Lin28A and c-Myc expression were assessed in PTC tissues and PTC cell lines using immunohistochemistry, Western blotting, and real-time PCR. CCK-8 and Transwell assays were performed to evaluate PTC cell proliferation, migration, and invasion in cells in which the expression of Lin28A was downregulated by RNA interference or in which let-7a was overexpressed after transfection with let-7a mimics. RESULTS The expression of Lin28A and c-Myc was upregulated in PTC tissues and cell lines, whereas the expression of let-7a was downregulated in PTC cell lines. Clinically, Lin28A was linked to a higher tumor/node/metastasis stage and the presence of lymph node metastases. Moreover, knockdown of Lin28A activated let-7a processing and inhibited the expression of the downstream gene c-Myc, suppressing cell proliferation, migration, and invasion. Similar results were obtained after let-7a overexpression. CONCLUSIONS The Lin28A/let-7a/c-Myc pathway is involved in cancer growth and malignant behavior in PTC and is a potential target for therapeutic intervention in this disease.

BACKGROUND This study was designed to assess the clinical efficacy and toxicity of apatinib (YN968D1) as third or subsequent-line treatment for stage III/IV non-small cell lung cancer (NSCLC). METHODS A total of 100 patients with advanced NSCLC who were treated with apatinib at a daily dose of 250/425/500 mg at Shandong Cancer Hospital from January 2016 to June 2018 were enrolled in our study. The objective response, disease control, and median progression-free survival rates were reviewed and evaluated. Univariate and multivariate analyses were performed to determine the prognostic factors. The main adverse events were evaluated per the Common Terminology Criteria for Adverse Events version 4.0. RESULTS All patients were assessable for response. No complete responses were observed, 11 patients achieved a partial response, and 56 showed stable disease. The objective response rate was 11.0%, the disease control rate was 67.0%, and the median progression-free survival was 2.93 months (95% confidence interval 2.07-3.87). In Cox regression analysis, the Eastern Cooperative Oncology Group performance status score (hazard ratio 1.799; P < 0.05) and smoking history (hazard ratio 1.958; P < 0.05) were predictive indicators for apatinib treatment efficacy. Treatment-related adverse events were tolerated, predictable, reversible, and controllable. CONCLUSION Apatinib was found to be both effective and safe in advanced NSCLC patients without a genetic driver mutation who experienced progression after two or more lines of chemotherapy treatment.

Enhancer of zeste homolog 2 inhibitors (EZH2i) have garnered increased attention owing to their anticancer activity by targeting EZH2, a well-known cancer-promoting factor. However, some lymphomas are resistant to EZH2i, and EZH2i treatment alone is ineffective in case of EZH2-overexpressing solid tumors. The anti-cancer efficacy of EZH2i may be improved through safe and effective combinations of these drugs with other treatment modalities. Preclinical evidence indicates that combining EZH2i with other therapies, such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy, has complementary or synergistic antitumor effects. Therefore, elucidating the underlying mechanisms of the individual constituents of the combination therapies is fundamental for their clinical application. In this review, we have summarized notable clinical trials and preclinical studies using EZH2i, their progress, and combinations of EZH2i with different therapeutic modalities, aiming to provide new insights for tumor treatment.

Coronavirus disease-2019 (COVID-19) pandemic has affected millions of people since December 2019. Summarizing the development of COVID-19 and assessing the effects of control measures are very critical to China and other countries. A logistic growth curve model was employed to compare the development of COVID-19 before and after the emergency response took effect. We found that the number of confirmed cases peaked 9–14 days after the first detection of an imported case, but there was a peak lag in the province where the outbreak was concentrated. Results of the growth curves indicated that the fitted cumulative confirmed cases were close to the actual observed cases, and the R2 of all models was above 0.95. The average growth rate decreased by 44.42% nationally and by 32.5% outside Hubei Province. The average growth rate in the 12 high-risk areas decreased by 29.9%. The average growth rate of cumulative confirmed cases decreased by approximately 50% after the emergency response. Areas with frequent population migration have a high risk of outbreak. The emergency response taken by the Chinese government was able to effectively control the COVID-19 outbreak. Our study provides references for other countries and regions to control the COVID-19 outbreak.

Dietary inadequacy is a major challenge among young children in Ghana. Nutritional policies are required for optimum child nutrition and development. This study explored food consumption and dietary diversity by socioeconomic status and geographical location among children aged 6–23 months in Ghana. We used the latest national representative, cross-sectional data from the Ghana Demographic and Health Survey (GDHS-2014). A total of 887 children aged 6–23 months were used in the final analysis. The survey collected data on children’s food consumption through their mothers in the 24 h recall method. Multiple logistic regression models were used to assess the relationship between socioeconomic status and geographical location with food consumption and adequate dietary diversity after adjusting for control variables. The study revealed an association between specific food item consumption, food groups, and dietary diversity by socioeconomic and geographic characteristics. However, dairy consumption increased faster than other nutritional foods when socioeconomic status increased. Furthermore, the study revealed that children’s chances of consuming particular food items and food groups differed across Ghana’s 10 regions. The average probabilities of consuming adequate dietary diversity between the Greater Accra region and Ashanti region were 43% vs. 8% (p &lt, 0.001). Consumption of grains, root, and tubers were relatively higher but low for Vitamin A-rich fruits and vegetables and legumes and nuts for children aged 6–23 months in Ghana. Overall, the mean dietary diversity score was low (3.39, 95% CI: 3.30–3.49) out of eight food groups, and the prevalence of adequate dietary diversity was 22% only. There is a need for policy interventions to ensure appropriate dietary practices to promote healthy growth of children.