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Aim. The study is aimed at exploring the relationship between newly graduated nurses’ transition shock, negative coping, job satisfaction, and intent to stay during the time of COVID-19. Background. The shortage of nurses is a global dilemma aggravated by the COVID-19 pandemic. It has been a hot topic in recent years to help newly graduated nurses transition smoothly. Transition shock is one of the essential indicators to describe the transition state of newly graduated nurses, which has a far-reaching impact on the intention of newly graduated nurses to stay in their posts. However, few studies have studied the mechanism behind this relationship, which may affect the effectiveness of retention strategies. Methods. A descriptive cross-sectional study was conducted from July to August 2021 in 31 tertiary hospitals in Shanghai, China. Participants comprised a convenience sample of 759 newly graduated nurses for surveys. Structural equation models were used to examine the study’s hypothetical model. Results. The results showed that transition shock had a significant direct effect on job satisfaction (b = −0.412, p < 0.001 ) and intent to stay (b = −0.145, p < 0.001 ). Job satisfaction had a significant direct effect on intent to stay (b = 0.702, p < 0.001 ). The indirect effect of transition shock on intent to stay through job satisfaction was statistically significant (b = −0.289), the 95% C.I. was (−0.493, −0.357), and the proportion of mediating effect to total effect was 66.59%. Moreover, the moderated mediation analysis showed that the interaction effect of transition shock and negative coping style on job satisfaction was significant (b = −0.082, p < 0.001 ). Conclusion. This study revealed the impact of transition shock on intent to stay of newly graduated nurses during the time of COVID-19, and found that job satisfaction played a mediating role and negative coping played a moderating role. These findings are of great significance for nursing managers to take measures to improve the intention of newly graduated nurses to stay. Implication for Nursing Management. The level of transition shock is an important indicator reflecting the transition state of newly graduated nurses, and can further predict the job satisfaction and intention of newly graduated nurses to stay. Therefore, nursing managers should pay attention to taking corresponding measures to reduce the level of transition shock of newly graduated nurses.

Aim To investigate the protective effect of α-lipoic acid on sodium arsenite (NaAsO2) induced INS-1 cells injury and its mechanism. Methods The cell viability was measured by CCK-8 assay. The autophagosomes was observed under transmission electron microscopy. The autophagosomes in cells transfected with green fluorescent protein microtubule-associated protein light chain 3 (GFP-LC3) plasmids were observed under a laser scanning con-focal microscope. The expression of LC3-II, P62, PI3K, and mTOR proteins in INS-1 cells treated with a combination of chloroquine (CQ, autophagy inhibitor) and NaAsO2 were detected by Western blot assay. The expression of LC3-II, P62, PI3K, and mTOR proteins were detected in INS-1 cells treated with a combination of rapamycin (autophagy inducer, mTOR inhibitor) and α-LA. Results The cytotoxicity induced by NaAsO2 was reversed by α-LA, and the viability of NaAsO2-treated INS-1 cells increased. α-LA pretreatment decreased the autophagosome accumulation induced by NaAsO2. α-LA also reduced the fluorescence spot aggregation of GFP-LC3 in INS-1 cells exposed to NaAsO2 as observed under a laser scanning con-focal microscope. α-LA inhibited NaAsO2 induced autophagy by up-regulating PI3K and mTOR and down-regulating LC3-II and P62. CQ inhibited NaAsO2 induced autophagy by up-regulating PI3K, mTOR, P62 and down-regulating LC3-II. α-LA inhibited rapamycin-induced autophagy by up-regulating PI3K, mTOR and P62 and down-regulating LC3-II. The results showed that NaAsO2 could induce autophagy activation in INS-1 cells. The α-LA may inhibit autophagy activation by regulating the PI3K/mTOR pathway. Conclusion The data indicated that α-LA might inhibit the NaAsO2-induced autophagic death of INS-1 cells by regulating the PI3K/mTOR pathway.

Objective：Coronary artery disease (CAD) is an immune-mediated chronic disease, and interleukin-27(IL-27) regulates CD4+ T cell differentiation. However, little is known about its effects on CAD. Therefore, we aimed to investigate the changes of IL-27 and its effect on CD4+ T cells in patients with CAD.Methods: The severity of coronary artery stenosis was assessed by Gensini score, and the concentrations of plasma IL-27, ox-LDL were measured by ELISA. qRT-PCR and Western Blotting (WB) were performed to evaluate the mRNA and protein expression of T-bet, IFN-γ, GATA-3, and RORγt. After monocytes were stimulated with recombinant IL-2 and/or IL-27, CD4+IFN-γ+T cells, CD4+IL-4+T cells, CD4+IL-17+T cells, CD4+LAP+T cells and CD4+CD25+Foxp3+ Tregs were counted by flow cytometry. Results: Plasma IL-27 levels were significantly elevated in patients with Acute Coronary Syndromes (ACS). IL-27 levels were positively correlated with ox-LDL and Gensini scores (P < 0.01) and ox-LDL levels were positively correlated with Gensini scores (P < 0.01). The more severe the stenosis in CAD patients, the more Th1 and Th17 cells, and the less Th2, CD4+CD25+Foxp3+Tregs and CD4+LAP+T cells. IL-27 can increase the expression of T-bet and IFN-γ, and inhibit the expression of RORγt and GATA-3, and finally promote the differentiation of CD4+T cells into Th1 cells, and inhibit the differentiation of Th2, Th17, CD4+CD25+Foxp3+Tregs and CD4+LAP+T cells.Conclusion: IL-27 regulates CAD by increasing the expression of T-bet and IFN-γ and inhibiting the expression of RORγt and GATA-3, thereby increasing the frequency of Th1 cells and decreasing the frequency of Th2, Th17, CD4+CD25+Foxp3+Tregs and CD4+LAP+T cells.

Background The role of sexually transmitted infections (STIs) in semen parameters and male infertility is still a controversial area. Previous studies have found bacterial infection in a minority of infertile leukocytospermic males. This study aims to investigate the prevalence of STIs in semen from subfertile men with leukocytospermia (LCS) and without leukocytospermia (non-LCS) and their associations with sperm quality. Methods Semen samples were collected from 195 men who asked for a fertility evaluation. Infection with the above 6 pathogens was assessed in each sample. Sperm quality was compared in subfertile men with and without LCS. Results The LCS group had significantly decreased semen volume, sperm concentration, progressive motility, total motility and normal morphology. The infection rates of Ureaplasma urealyticum (Uuu), Ureaplasma parvum (Uup), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), herpes simplex virus-2 (HSV-2) and Neisseria gonorrhoeae (NG) were 8.7 %, 21.0 %, 8.2 %, 2.1 %, 3.6 %, 1.0 and 0 %, respectively. The STI detection rates of patients with LCS were higher than those of the non-LCS group (52.3 % vs. 39.3 %), although there was no statistically significant difference between the two groups (P = 0.07). All semen parameters were not significantly different between LCS with STIs and without STIs, except the semen volume in the MG-infected patients with LCS was significantly lower than that in the noninfected group. Conclusions LCS was associated with a reduction in semen quality, but was not associated with STIs.

Background Delivery of therapeutic small interfering RNA (siRNA) via functionalized nanoparticles holds great promise for cancer therapy. However, developing a safe and efficient delivery carrier of siRNA is a challenging issue. Methods RGDfC peptide was used to modify the surface of selenium nanoparticles (SeNPs) to synthesize a biocompatible siRNA delivery vehicle (R-SeNPs), and MEF2D-siRNA was loaded onto R-SeNPs to prepare a functionalized selenium nanoparticle R-Se@MEF2D-siRNA. The chemical properties of R-SeNPs were characterized, and the anticancer efficacy as well as related mechanisms of R-Se@MEF2D-siRNA were further explored. Results R-Se@MEF2D-siRNA was significantly taken up by SKOV3 cells and could enter SKOV3 cells mainly in the clathrin-associated endocytosis way. The result of in vitro siRNA release demonstrated that R-Se@MEF2D-siRNA could release MEF2D-siRNA quicker in a microenvironment simulating a lysosomal environment in tumor cells compared to a normal physiological environment. The results of qRT-PCR assay proved that R-Se@MEF2D-siRNA could effectively silence the expression of the MEF2D gene in SKOV3 cells. R-Se@MEF2D-siRNA remarkably suppressed the proliferation of SKOV3 cells and further triggered its apoptosis. In addition, R-Se@MEF2D-siRNA had the capability to disrupt mitochondrial membrane potential (MMP) in SKOV3 cells and resulted in the overproduction of reactive oxygen species (ROS), indicating that mitochondrial dysfunction and ROS generation played an important role in the apoptosis of SKOV3 cells induced by R-Se@MEF2D-siRNA. In vivo, R-Se@MEF2D-siRNA also exhibited excellent antitumor activity mainly through decreasing tumor cells proliferation and triggering their apoptosis in tumor-bearing nude mice. Conclusion R-Se@MEF2D-siRNA provides an alternative strategy for ovarian cancer treatment in the clinic.

Objective To characterize the inferior adrenal artery (IAA) pulsatility index (PI) in intrauterine growth–restricted (IUGR) fetuses without brain sparing. Methods Twenty-three IUGR fetuses with a normal Doppler cerebroplacental ratio (CPR) and 23 normal controls were included in this prospective cross-sectional study. The PI of the IAA was recorded using routine transabdominal Doppler ultrasound. The differences in Doppler characteristics, perinatal outcomes, and steroidogenesis in the umbilical vein at birth (adrenocorticotropic hormone [ACTH] and cortisol [F] levels) were compared between the 2 groups. The correlations between IAA-PI and steroidogenesis were assessed in the IUGR group. Results IAA-PI was significantly lower in IUGR fetuses than in normal controls (0.85 vs 1.18 at first scan, 0.78 vs 0.92 at last scan; both P < 0.001). The plasma F and ACTH levels in IUGR cases were significantly higher than those of the normal controls (18.2 vs 12.4 µg/dL and 280.5 vs 125.6 pg/mL for F and ACTH, respectively; both P < 0.001). There were negative correlations between IAA-PI and plasma F values and between IAA-PI and ACTH values in the IUGR group (r = −0.774 and −0.82 at first scan, r = −0.525 and −0.45 at last scan, respectively; P < 0.001). Conclusion Increased adrenal gland blood flow with concomitant increases in ACTH and F levels were observed in IUGR fetuses. IAA-PI is useful to assess early blood redistribution and may be beneficial for evaluating the steroidogenic response in high-risk pregnancies.

Mobile crowdsourcing enables mobile requesters to publish tasks, which can be accomplished by workers with awards. However, existing task allocation schemes face tradeoff between effectiveness and privacy preservation, and most of them lack consideration of win-win incentives for both requesters and workers participation. In this paper, we propose a privacy-preserving task recommendation scheme with win-win incentives in crowdsourcing through developing advanced attribute-based encryption with preparation/online encryption and outsourced decryption technologies. Specifically, we design bipartite matching between published tasks and participant workers, to recommend tasks for eligible workers with interests and provide valuable task accomplishment for requesters in a win-win manner. Furthermore, our scheme reduces encryption cost for requesters by splitting encryption into preparation and online phases, as well as shifts most of the decryption overhead from the worker side to the service platform. Privacy analysis demonstrates requester and worker privacy preservation under chosen-keyword attack and chosen-plaintext attack. Performance evaluation shows cost-efficient computation overhead for requesters and workers.

In this paper, we consider the issue of the secure transmissions for the cognitive radio-based Internet of Medical Things (IoMT) with wireless energy harvesting. In these systems, a primary transmitter (PT) will transmit its sensitive medical information to a primary receiver (PR) by a multi-antenna-based secondary transmitter (ST), where we consider that a potential eavesdropper may listen to the PT’s sensitive information. Meanwhile, the ST also transmits its own information concurrently by utilizing spectrum sharing. We aim to propose a novel scheme for jointly designing the optimal parameters, i.e., energy harvesting (EH) time ratio and secure beamforming vectors, for maximizing the primary secrecy transmission rate while guaranteeing secondary transmission requirement. For solving the nonconvex optimization problem, we transfer the problem into convex optimization form by adopting the semidefinite relaxation (SDR) method and Charnes–Cooper transformation technique. Then, the optimal secure beamforming vectors and energy harvesting duration can be obtained easily by utilizing the CVX tools. According to the simulation results of secrecy transmission rate, i.e., secrecy capacity, we can observe that the proposed protocol for the considered system model can effectively promote the primary secrecy transmission rate when compared with traditional zero-forcing (ZF) scheme, while ensuring the transmission rate of the secondary system.

This study aimed to investigate the alteration of circulating CD34In this study, 36 patients with newly diagnosed type 2 diabetes and 22 control subjects matched by age and gender were enrolled. All of the patients with diabetes received intensive insulin therapy. The number of EPCs was assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor (KDR).Levels of circulating CD34These results showed that type 2 diabetes is associated with an increase of circulating CD34NCT03710811.

Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related deaths worldwide. Overexpression of pleomorphic adenoma gene like‐2 (PLAGL2) is associated with tumorigenesis. However, its function in HCC is unclear, and there are currently no anti‐HCC drugs that target PLAGL2. Drug repositioning may facilitate the development of PLAGL2‐targeted drug candidates. Methods The expression of PLAGL2 in HCC clinical tissue samples and HCC cell lines was analyzed by western blotting. The constructed HCC cell models were used to confirm the underlying function of PLAGL2 as a therapeutic target. Multiple in vitro and in vivo assays were conducted to determine the anti‐proliferative and apoptosis‐inducing effects of selenium sulfide (SeS2), which is clinically used for the treatment of seborrheic dermatitis and tinea versicolor. Results PLAGL2 expression was higher in HCC tumor tissues than in normal adjacent tissues. Its overexpression promoted the resistance of HCC cells of mitochondrial apoptosis through the regulation of the downstream C‐MET/STAT3 signaling axis. SeS2 exerted significant anti‐proliferative and apoptosis‐inducing effects on HCC cells in a PLAGL2‐dependent manner. Mechanistically, SeS2 suppressed C‐MET/STAT3, AKT/mTOR, and MAPK signaling and triggered Bcl‐2/Cyto C/Caspase‐mediated intrinsic mitochondrial apoptosis both in vitro and in vivo. Conclusions Our data reveal an important role of PLAGL2 in apoptosis resistance in HCC and highlight the potential of using SeS2 as a PLAGL2 inhibitor in patients with HCC., The C‐MET/STAT3 signaling axis as a novel downstream target of pleomorphic adenoma gene like‐2 (PLAGL2) contributed to PLAGL2‐induced mitochondrial apoptosis resistance in HCC. Selenium sulfide (SeS2) induced cell proliferation inhibition and apoptosis on HCC cells by inhibiting the activity of PLAGL2 and restraining the novel PLAGL2/C‐MET/STAT3, AKT/mTOR and MAPK signaling pathways.

The rise of smart health promotes ubiquitous healthcare services with the adoption of information and communication technologies. However, increasing demands of medical services require more computing and storage resources in proximity of medical users for intelligent sensing, processing, and analysis. Fog computing emerges to enable in situ data processing and service provision for smart health in proximity of medical users, exploiting a large number of small-scale servers. In this article, we investigate fog-enabled smart health toward cooperative and secure healthcare service provision. Specifically, we first introduce the overall infrastructure and some promising applications, including emergent healthcare service, health risk assessment, and healthcare notification. We then discuss the challenges of fog-enabled smart health from the perspectives of cooperation and security. A case study is presented to demonstrate efficient and secure health data sharing through naive Bayes classification and attribute-based encryption with assistance from fog computing. Finally, by exploring interesting future directions, more attention can be attracted to this emerging area.

Infantile-onset inflammatory bowel disease can be caused by defects in interleukin-10 signalling. The natural history and clinical outcomes of allogeneic haematopoietic stem cell transplantation, medical treatment and surgery have not been thoroughly described.This study evaluates disease progression and clinical outcome in patients with interleukin-10 signalling deficiency.One hundred and nine patients with interleukin-10 signalling deficiency were retrospectively reviewed from a single tertiary centre. The Kaplan-Meier method was applied to calculate probabilities of survival and interval between transplant and stoma closure.One hundred and nine patients were reviewed, and 102 patients were included in the survival analysis. One hundred and eight patients were identified with IL10RA mutations, and one patient harboured IL10RB mutation. Seventy-three patients received haematopoietic stem cell transplantation. The overall survival after transplantation was 64.2% (95% confidence interval, 52.8 to 75.6), and without transplantation, it was 47.5% (95% confidence interval, 14.8 to 80.2, P = 0.47). The median timeframe between transplant and stoma closure was 19.6 months. The probability of survival was significantly lower in patients with perforation (P 0.001), ileus (P = 0.038) and without thalidomide treatment (P 0.001) among patients who did not receive haematopoietic stem cell transplantation. The survival probability was not associated with timeframe between transplant and onset, graft source and genotypes.The survival probability was not significantly different between patients with transplantation and the non-transplanted patients.

Objective The objective of this study was to determine fetal foramen ovale blood flow utilizing pulsed Doppler combined with spatiotemporal image correlation. Methods A cross-sectional study was performed in 440 normal fetuses between 20 and 40 weeks of gestation. In order to calculate foramen ovale blood flow, the foramen ovale flow velocity–time integral was obtained by pulsed Doppler ultrasonography, and the foramen ovale area was measured by using spatiotemporal image correlation rendering mode. Foramen ovale blood flow was calculated as the product of the foramen ovale area and the velocity–time integral. Results Gestational age-specific reference ranges are given for the absolute blood flow (ml/min) of foramen ovale, showing an exponential increase from 20 to 30 weeks of gestation, and a flat growth trend during the last trimester, while the weight-indexed flow (ml/min/kg) of foramen ovale decreased significantly. The median weight-indexed foramen ovale blood flow was 320.82 ml/min/kg (mean 319.1 ml/min/kg; SD 106.33 ml/min/kg). Conclusions The reference range for fetal foramen ovale blood flow was determined from 20 to 40 weeks of gestation. The present data show that the volume of foramen ovale blood flow might have a limited capacity to increase during the last trimester.

Coronavirus Disease 2019 (COVID‐19) cases and deaths are still rising worldwide, there is currently no effective treatment for severe inflammation and acute lung injury caused by new coronavirus (SARS‐COV‐2) infection. Therapies to prevent or treat COVID‐19, including antiviral drug and several vaccines, are still being development. Human angiotensin‐converting enzyme 2 (ACE2), expressing in lung, has been confirmed to be a receptor for SARS‐COV‐2 infection, interventions for attachment of spike protein of SARS‐CoV‐2 to ACE2 may be a potential approach to prevent viral infections and it is considered as a potential target for drug development. In this study, we observed that seabuckthorn and its flavonoid compounds quercetin and isorhamnetin were shown strong retention to ACE2 overexpression HEK293 (ACE2h) cells by CMC analysis. Based on drug receptor interaction analysis and viral entry studies in vitro, we evaluated the interaction of two flavonoid compounds and ACE2 as well as the inhibitory effect of the two compounds on viral entry. Surface plasmon resonance assay proved the effect that isorhamnetin bound to the ACE2, and its affinity (KD value) was at the micromolar level, that was, 2.51 ± 0.68 μM. Viral entry studies in vitro indicated that isorhamnetin inhibited SARS‐CoV‐2 spike pseudotyped virus entering ACE2h cells. Based on promising in vitro results, we proposed isorhamnetin to be a potential therapeutic candidate compound against COVID‐19.

Although the thin endometrium (TE) has been widely recognized as a critical factor in implantation failure, the contribution of miRNA–mRNA regulatory network to the development of disease etiology remains to be further elucidated. This study performed an integrative analysis of the miRNA–mRNA expression profiles in the thin and adjacent normal endometrium of eight patients with intrauterine adhesion to construct the transcriptomic regulatory networks. A total of 1,093 differentially expressed genes (DEGs) and 72 differentially expressed miRNAs (DEMs) were identified in the thin adhesive endometrium of the TE group compared with the control adjacent normal endometrial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs and the target genes of DEM were significantly enriched in angiogenesis, cell growth regulation, and Wnt signaling pathway. Multiple hub genes (CAV1, MET, MAL2, has-mir-138, ARHGAP6, CLIC4, RRAS, AGFG1, has-mir-200, and has-mir-429) were identified by constructing the miRNA–mRNA regulatory networks. Furthermore, a miRNA–mRNA pathway function analysis was conducted, and the hub genes were enriched in the FoxO signaling pathway, cell growth regulation, inflammatory response regulation, and regulation of autophagy pathways. Our study is the first to perform integrated mRNA-seq and miRNA-seq analyses in the thin adhesive endometrium and the control adjacent normal endometrial cells. This study provides new insights into the molecular mechanisms underlying the formation of thin endometrium.

BackgroundCpG island methylator phenotype (CIMP), featured with concurrent and widespread hypermethylation of a cluster of CpGs, has been reported to play an important role in carcinogenesis. Limited studies have investigated the CIMP in pancreatic cancer (PC). The aim of this study was to explore the CIMP in PC patients and its clinical-pathological and genomic characteristics. Methods:DNA methylation, somatic mutation, mRNA and corresponding clinical data of PC patients were downloaded from TCGA (184 patients) and ICGC (264 patients). Univariate and multivariate regression analysis were used to identify prognosis related CpGs. Consensus clustering analysis was used for identification of the CIMP in PC patients. ESTIMATE and CIBORORT were used for estimation of tumor microenvironment (TME) in PC patients.ResultsIn TCGA PC cohort, 22,450 differential CpGs, including 12,937 hypermethylated CpGs and 9,513 hypomethylated CpGs were identified between185 PC patients and 10 normal controls. Univariate and multivariate Cox analysis further screened out 72 OS related CpGs and three distinct CIMP groups with distinctly different prognosis and molecular features, including CIMP-L subgroup, CIMP-M subgroup and CIMP-H subgroup were identified based on unsupervised consensus clustering analysis of these CpGs. Patients of the CIMP-H subgroup had poorer OS and RFS, while patients of CIMP-L subgroup had better OS and RFS. The CIMP status were also an independent prognostic factors for OS and PFS. In molecular features, significantly higher somatic mutation burdens and tumor mutational burden were found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. Besides, lower stromal score, immune score and higher cancer stemness indices and tumor purity were also found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. Correspondingly, significantly total T cells, total B cells, CD8 T cells, memory CD4 T cells and higher regulatory T cells were found at patients of CIMP-H subgroup. Moreover, significantly lower expression of immune checkpoint genes, such as PD-1, CTLA4, CD86, VTCN1 and LAG-3 were also found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. In the end, we validated the CIMP status in PC patients of ICGC dataset.ConclusionThree distinct CIMP subgroups of PC patients with distinct clinical characteristic, prognosis, gene mutation landscape and TME were identified and validated. The CIMP may help to make an assertion to provide specific and efficient treatment options for patients of different subtypes.

Background. Liver cirrhosis is one of the major drivers of hepatocellular carcinoma (HCC). In the present study, we aimed to identify and validate new biomarker for early prediction of HCC development in early-stage cirrhosis patients. Methods. mRNA expression and clinical parameters of GSE63898, GSE89377, GSE15654, GSE14520, and TCGA-HCC cohort and ICGC-HCC cohort were downloaded for analysis. Wilcoxon test was performed to identify DEGs. Univariate and multivariate Cox regression analysis were used to develop the risk signature, and ROC analysis was performed to analyze the predictive accuracy and sensitivity of the risk signature. Results. There were 42 DEGs (including 28 upregulated genes and 14 downregulated genes) found in early-stage liver cirrhosis patients before developing HCC from GSE1565442. Then, a risk signature consisting of 8 DEGs could effectively classify early-stage cirrhosis patients into high-risk group with shorter HCC development time and low-risk group with longer HCC development time from GSE15654. Multivariate Cox analysis indicated that the risk signature was an independent prognostic factor for the prediction of HCC development and ROC analysis showed that the signature exhibited good predictive efficiency in predicting 2-, 5-, and 10-year HCC development. Mechanistically, significantly higher proportions of CD8 T cells were found to be enriched in cirrhosis patients with low risk score, and higher CD8 T cells were associated with longer HCC development time. Besides, the signature was an independent prognostic factor for poorer prognosis of early-stage liver cirrhosis patients of GSE15654. Moreover, the signature could also separate HCC patients from healthy controls and was also associated with the poorer prognosis of HCC patients from three HCC cohorts. Finally, we also identified HDAC inhibitors, such as trichostatin A, to be a potential chemopreventive treatment for the prevention of HCC development by targeting risk signature based on CMap analysis. Conclusion. A risk signature was developed and validated for early prediction of HCC development, which may be a useful tool to set up individualized follow-up interval schedules.

Background. CpG island methylator phenotype (CIMP), featured with concurrent and widespread hypermethylation of a cluster of CpGs, has been reported to play an important role in carcinogenesis. Limited studies have investigated the role of CIMP in pancreatic cancer (PC). The aim of this study was to explore the CIMP in PC patients and its impact on the immune response of the tumor microenvironment and prognosis. Methods. DNA methylation, somatic mutation, mRNA, and corresponding clinical data of PC patients were downloaded from TCGA (184 patients) and the ICGC (264 patients). Univariate and multivariate regression analyses were used to identify prognosis-related CpGs. Consensus clustering analysis was used for identification of the CIMP in PC patients. ESTIMATE and CIBORORT were used for estimation of the tumor microenvironment (TME) in PC patients. Results. In the TCGA PC cohort, 22,450 differential CpGs, including 12,937 hypermethylated CpGs and 9,513 hypomethylated CpGs, were identified between 184 PC patients and 10 normal controls. Univariate and multivariate Cox analysis further screened out 72 OS-related CpGs, and three distinct CIMP groups with distinctly different prognosis and molecular features, including the CIMP-L subgroup, CIMP-M subgroup, and CIMP-H subgroup, were identified based on unsupervised consensus clustering analysis of these CpGs. Patients of the CIMP-H subgroup had poorer OS and RFS, while patients of the CIMP-L subgroup had better OS and RFS. The CIMP status was also an independent prognostic factor for OS and PFS. In molecular features, significantly higher somatic mutation burden and tumor mutational burden were found in patients of the CIMP-H subgroup compared to those of the CIMP-L subgroup. Besides, lower stromal score, immune score, and higher cancer stemness indices and tumor purity were also found in patients of the CIMP-H subgroup compared to those of the CIMP-L subgroup. Correspondingly, significant total T cells, total B cells, CD8 T cells, memory CD4 T cells, and higher regulatory T cells were found in patients of the CIMP-H subgroup. Moreover, significantly lower expression of immune checkpoint genes, such as PD-1, CTLA4, CD86, VTCN1, and LAG-3, was also found in patients of the CIMP-H subgroup compared to those of the CIMP-L subgroup. In the end, we validated the CIMP status in PC patients of the ICGC dataset. Conclusion. The CIMP may modulate the immune response of the tumor microenvironment and influence the prognosis of pancreatic cancer patients, which may help to make an assertion to provide specific and efficient treatment options for patients of different subtypes.

Background Delivery of therapeutic small interfering RNA (siRNA) via functionalized nanoparticles holds great promise for cancer therapy. However, developing a safe and efficient delivery carrier of siRNA is a challenging issue. Methods RGDfC peptide was used to modify the surface of selenium nanoparticles (SeNPs) to synthesize a biocompatible siRNA delivery vehicle (R-SeNPs), and MEF2D-siRNA was loaded onto R-SeNPs to prepare a functionalized selenium nanoparticle R-Se@MEF2D-siRNA. The chemical properties of R-SeNPs were characterized, and the anticancer efficacy as well as related mechanisms of R-Se@MEF2D-siRNA were further explored. Results R-Se@MEF2D-siRNA was significantly taken up by SKOV3 cells and could enter SKOV3 cells mainly in the clathrin-associated endocytosis way. The result of in vitro siRNA release demonstrated that R-Se@MEF2D-siRNA could release MEF2D-siRNA quicker in a microenvironment simulating a lysosomal environment in tumor cells compared to a normal physiological environment. The results of qRT-PCR assay proved that R-Se@MEF2D-siRNA could effectively silence the expression of the MEF2D gene in SKOV3 cells. R-Se@MEF2D-siRNA remarkably suppressed the proliferation of SKOV3 cells and further triggered its apoptosis. In addition, R-Se@MEF2D-siRNA had the capability to disrupt mitochondrial membrane potential (MMP) in SKOV3 cells and resulted in the overproduction of reactive oxygen species (ROS), indicating that mitochondrial dysfunction and ROS generation played an important role in the apoptosis of SKOV3 cells induced by R-Se@MEF2D-siRNA. In vivo, R-Se@MEF2D-siRNA also exhibited excellent antitumor activity mainly through decreasing tumor cells proliferation and triggering their apoptosis in tumor-bearing nude mice. Conclusion R-Se@MEF2D-siRNA provides an alternative strategy for ovarian cancer treatment in the clinic.

Background Exposure to high ergonomic risk resulted in an increasing prevalence of musculoskeletal disorders among dental professional. However, little is known about the high exposure risk impact on work ability among dental professionals. Objective We conducted a cross-sectional study to examine the association between ergonomic risk exposure and work ability among young dental professionals in their early careers. Methods A total of 230 dental professionals including dentists, dental assistants, and nurses were clustered sampled from three hospitals in Guangzhou, south of China. We used the Quick Ergonomic Check (QEC) to assess participants' ergonomic risk exposure and Work Ability Index (WAI) to evaluate their work ability. Demographics and other factors related with WAI were also included in the data collection. Multiple linear regression was applied to analyze the association between ergonomic exposure scores and WAI. Results A total of 218 participants (94.8%) had valid data and consent forms. The participants' average WAI was 39.6, of which the poor and moderate WAI composed 31%. High and very high ergonomic risk exposure level was 45.9% for the neck and 21.1% for the wrist/hand. In general, WAI decreased with higher ergonomic exposure level. With adjustment of other potential risk factors, the ergonomic scores for wrist/hand and total scores for the whole body were significantly associated with the decreased WAI. Conclusion High ergonomic risk exposure might risk in reducing work ability among young dental professionals. Intervention measures toward ergonomic risk should be taken to prevent WAI from decreasing in their early careers.