A new modality of colorectal cancer screening based on chronic disease management.

BACKGROUND: To develop a new modality of colorectal cancer screening based on chronic disease management (CDM) to improve the participation rate of screening, and maximize the benefits of limited resources. METHODS: Patients under CDM were assigned to screening intervention group (SI) and screening control group1 (SC1), residents from natural community were assigned to screening control group2 (SC2). A parallel controlled community intervention study was performed. Only SI would achieve "one-to-one" intervention services. Meanwhile, 200 subjects were selected from each of the three groups for the Knowledge-Attitude-Practice (KAP) questionnaire before and after intervention, named questionnaire intervention group(QI), questionnaire control group1(QC1) and questionnaire control group2(QC2). The outcome of the intervention was evaluated using the difference-in-differences method and multiple regression analysis. RESULTS: The preliminary screening participation rate was 43.63%(473/1084) in SI, 14.32%(132/922) in SCI, and 5.87%(105/1789) in SC2. The baseline questionnaire showed low knowledge scores in the three questionnaire groups with no statistically significant differences, while attitude scores in QI and QC1 were significantly higher than QC2. The differences between baseline and terminal showed QI increased larger in knowledge and attitude scores than QC1 and QC2, while no difference was detected between QC1 and QC2. CONCLUSION: The colorectal cancer screening model based on chronic disease management effectively improved the screening participation rate, and the "one-to-one" intervention and the inherent characteristics of the patient population under CDM were the core elements of the new modality.

Potential intestinal infection and faecal-oral transmission of human coronaviruses.

Human coronaviruses (HCoVs) were first described in 1960s for patients experiencing common cold. Since then, increasing number of HCoVs have been discovered, including those causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the circulating coronavirus disease 2019 (COVID-19), which can cause fatal respiratory disease in humans on infection. HCoVs are believed to spread mainly through respiratory droplets and close contact. However, studies have shown that a large proportion of patients with HCoV infection develop gastrointestinal (GI) symptoms, and many patients with confirmed HCoV infection have shown detectable viral RNA in their faecal samples. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal HCoV infection. These data highlight the nature of HCoV GI infection and its potential faecal-oral transmission. Here, we summarise the current findings on GI manifestations of HCoVs. We also discuss how HCoV GI infection might occur and the current evidence to establish the occurrence of faecal-oral transmission.

Pseudotyped Viruses for Orthohantavirus.

Orthohantaviruses, members of the Orthohantavirus genus of Hantaviridae family of the Bunyavirales order, are enveloped, negative-sense, single-stranded, tripartite RNA viruses. They are emerging zoonotic pathogens carried by small mammals including rodents, moles, shrews, and bats and are the etiologic agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) among humans. With the characteristics of low biological risk but strong operability, a variety of pseudotyped viruses have been constructed as alternatives to authentic orthohantaviruses to help delineate the roles of host factors in viral entry and other virus-host interactions, to assist in deciphering mechanisms of immune response and correlates of protection, to enhance our understanding of viral antigenic property, to characterize viral entry inhibitors, and to be developed as vaccines. In this chapter, we will discuss the general property of orthohantavirus, construction of pseudotyped orthohantaviruses based on different packaging systems, and their current applications.

Integrative proteomics and phosphoproteomics profiling on osteogenic differentiation of periodontal ligament stem cell.

This study aims to elucidate the phosphorylated profile of periodontal ligament stem cells (PDLSCs) osteogenic differentiation, which contributes to the promotion of periodontium regeneration. PDLSCs cultured in the osteogenic induction medium for 14 days were analyzed by proteomics and phosphoproteomics. Potential functions of phosphorylated differentially expressed proteins (DEPs) were annotated and enriched based on Gene Ontology (GO). Furtherly, overlapped DEPs were identified and conducted protein-protein interaction (PPI) network united with the top 20 up/downregulated phosphorylated DEPs. Hub phosphorylated DEPs were analyzed by Cytoscape, and the protein kinase phosphorylation network was predicted by iGPS. Proteomics identified 87 upregulated and 227 downregulated DEPs. Phosphoproteomics identified 460 upregulated and 393 downregulated phosphorylated DEPs, and they were primarily enriched in mitochondrial function and ion-channel related terms. Furthermore, 63 overlapped DEPs were recognized for more accurate predictions. Among the top 10 hub phosphorylated DEPs, only Integrin alpha-5 (ITGA5) expressed upregulated phosphorylation, and half of them belonged to extracellular matrix (ECM) proteins. In addition, numerous kinases corresponding to four interactive hub phosphorylated DEPs were predicted, including Collagen alpha-2(I) (COL1A2), Syndecan-1 (SDC1), Fibrillin-1 (FBN1), and ITGA5. Our findings established a basis for further elucidation of the phosphorylation of PDLSCs osteogenic differentiation, and COL1A2/SDC1/ITGA5/FBN1 phosphorylated network may dominate this process.

mTORC1 promotes mineralization via p53 pathway.

The objectives of our study were to investigate the roles of mTORC1 in odontoblast proliferation and mineralization and to determine the mechanism by which mTORC1 regulates odontoblast mineralization. In vitro, MDPC23 cells were treated with rapamycin (10 nmol/L) and transfected with a lentivirus for short hairpin (shRNA)-mediated silencing of the tuberous sclerosis complex (shTSC1) to inhibit and activate mTORC1, respectively. CCK8 assays, flow cytometry, Alizarin red S staining, ALP staining, qRT-PCR, and western blot analysis were performed. TSC1-conditional knockout (DMP1-Cre+ ; TSC1f/f , hereafter CKO) mice and littermate control (DMP1-Cre- ; TSC1f/f , hereafter WT) mice were generated. H&E staining, immunofluorescence, and micro-CT analysis were performed. Transcriptome sequencing analysis was used to screen the mechanism of this process. mTORC1 inactivation decreased the cell proliferation. The qRT-PCR and western blot results showed that mineralization-related genes and proteins were downregulated in mTORC1-inactivated cells. Moreover, mTORC1 overactivation promoted cell proliferation and mineralization-related gene and protein expression. In vivo, the micro-CT results showed that DV/TV and dentin thickness were higher in CKO mice than in controls and H&E staining showed the same results. Mineralization-related proteins expression was upregulated. Transcriptome sequencing analysis revealed that p53 pathway-associated genes were differentially expressed in TSC1-deficient cells. By inhibiting p53 alone or both mTORC1 and p53 with rapamycin and a p53 inhibitor, we elucidated that p53 acts downstream of mTORC1 and that mTORC1 thereby promotes odontoblast mineralization. Taken together, our findings demonstrate that the role of mTORC1 in odontoblast proliferation and mineralization, and confirm that mTORC1 upregulates odontoblast mineralization via the p53 pathway.

Lysophosphatidic acid mediated PI3K/Akt activation contributed to esophageal squamous cell cancer progression.

Lysophosphatidic acid (LPA) and its G-protein-coupled receptors (Lpar1-Lpar6) mediate a plethora of activities associated with cancer growth and progression. However, there is no systematic study about whether and how LPA promotes esophageal squamous cell carcinoma (ESCC). Here, we show that autotaxin (ATX), a primary LPA-producing enzyme, is highly expressed in ESCC, and overexpressed ATX is associated with the poor outcome of ESCC patients. Meanwhile, the expression of Lpar1 was much higher in ESCC cells compared with Het-1a (human esophagus normal epithelial cells). Functional experiments showed that LPA remarkably increased the proliferation and migration of ESCC cells. Furthermore, Lpar1 knockdown abolished the effect of LPA on ESCC cell proliferation and migration. Mechanistic studies revealed that LPA promoted ESCC cell lines proliferation and migration through PI3K/Akt pathway. Treatment of KYSE30 cell xenografts with Lpar1 inhibitor BMS-986020 significantly repressed tumor growth. Our results shed light on the important role of LPA in ESCC, and Lpar1 might be a potential treatment target for ESCC.

Ferrostatin-1 alleviated TNBS induced colitis via the inhibition of ferroptosis.

Inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing and life-threatening inflammatory disorder that mainly affect the intestinal tract. The mainstream therapies for moderate to severe IBD lie in the use of immunosuppressive agents. However, it encountered the problem of drug tolerance and significant adverse events. Therefore, identifying novel signal pathways involved in IBD is necessary to satisfy the unmet treatment needs of IBD patients. There existed some hints between iron and IBD, and was reported that ferroptosis induced in UC. However, as another important subtype of IBD, whether ferroptosis also occurred in CD remains unclear. In this study, we found that the dysregulation of iron, lipid peroxidation and redox homeostasis were involved in CD; the administration of ferroptosis inhibitor Ferrostatin-1 could alleviate pathological phenotypes of TNBS induced CD-like colitis in mice. Our results provide a new hopeful therapeutic strategy in treating CD, especially for those who suffered from the tolerance of existing immunosuppressive agent drugs.

Heparin locks with low and high concentration in haemodialysis patients: A systematic review and meta-analysis.

AIM: There is no evidence-based consensus on the optimal concentration for heparin locks; several randomized controlled trials (RCTs) have evaluated the concentration of heparin locks, yet the results remain inconsistent. We aimed to assess heparin locks with low and high concentration in haemodialysis patients. METHODS: We performed a systematic review and meta-analysis of RCTs focusing on the concentration in heparin locks. Studies were identified by searching PUBMED, EMBASE, Science Direct, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI) and Wanfang databases (from inception to 15 March 2020). Summary risk ratios or mean differences with 95% confidence interval were calculated. RESULTS: A total of 370 patients with four RCTs were included. Heparin locks with 1000 U/ml could significantly reduce the activated partial thromboplastin time (APTT) compared with 5000 U/ml. No significant differences were seen in the occurrence of catheter-related thrombosis, the length of catheter stay, the rates of bleeding and catheter occlusions between the two groups. CONCLUSIONS: Lower concentrations in heparin lock are optimal for shortening APTT in haemodialysis patients; further studies are needed to elucidate the role of heparin concentration in the lock practice.

Antigenic Drift of Influenza A(H7N9) Virus Hemagglutinin.

Background: Since the emergence of influenza A(H7N9) virus in 2013, there have been 5 waves of influenza A(H7N9) epidemics in China. However, evolution of the hemagglutinin (HA) protein antigenicity has not been systematically investigated. Methods: To better understand how antigenic drift in HA proteins of influenza (A)H7N9 virus occurs, 902 influenza A(H7N9) virus HA protein sequences from a public database were retrieved and analyzed. Fifty-three mutants with single amino acid substitutions in HA protein were introduced into pseudoviruses, and their antigenic characteristics were analyzed using pseudovirus-based assays. Results: The frequencies of 9 mutations incrementally increased over the past 5 years, with mutations identified at multiple sites. While mean neutralization titers of most variants remained unchanged, 3 mutations, A143V, A143T, and R148K, displayed a median 4-fold lower susceptibility to neutralization by antisera against influenza A/Anhui/1/2013(H7N9) virus. Notably, A143V and A143T were located outside the previously reported antigenic sites. The most dominant variant (A143V/R148K) in the most recent season constituted 74.11% of all mutations and demonstrated a 10-fold reduction in its reactivity to influenza A/Anhui/1/2013(H7N9) virus antisera. Importantly, compared with the DNA construct without the corresponding HA protein mutation, DNA vaccine encoding the A143V/R148K mutant induced a 5-fold increase in the neutralizing activity against this circulating virus. Conclusions: An appropriate vaccine strain should be considered in response to increasing antigenic drift in influenza A(H7N9) virus HA protein.

Priming integrin α5 promotes human dental pulp stem cells odontogenic differentiation due to extracellular matrix deposition and amplified extracellular matrix-receptor activity.

Our previous study showed that knocking down integrin α5 (ITGA5) expression by using a lentiviral vector in human dental pulp stem cells (DPSCs) led to weakening proliferation and migration capacity while enhanced odontogenic differentiation. To seek for possible clinical application, we investigated the effect of the ITGA5 priming synthetic cyclic peptide (SCP; GA-CRRETAWAC-GA) on proliferation, migration, and the odontogenic differentiation of DPSCs. Remarkably, the involved mechanism was explored by isobaric tag for relative and absolute quantitation proteomic technique, and the in vivo effect of ITGA5 was investigated by nude mice subcutaneous transplantation of cell and hydroxyapatite/ß-tricalcium phosphate complex. Results showed that SCP weakened the proliferation and migration capacity while enhanced odontogenic differentiation of DPSCs as lentivirus. The phosphorylation of FAK, PI3K/AKT, and MEK1/2/ERK1/2, along with IGF2/IGFBP2 and Wnt/ß-catenin signaling pathway play an important role in this process. Proteomic Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the key role of extracellular matrix (ECM) and ECM-receptor activity pathway were involved. ECM constituents, secreted protein acidic and cysteine-rich (SPARC), lumican, vitronectin, prolargin, decorin, collagen type VI α1 chain (COL6A1), COL6A2, COL14A1, and COL5A1 were upregulated in the ITGA5-silenced group. Inhibited expression of ITGA5 in DPSCs increased osteoid tissue formation and stronger related genes expression in vivo. In conclusion, the ITGA5 priming peptide could promote DPSCs odontogenic differentiation as lentivirus. Proteomics and bioinformatic analysis revealed that this may be due to the deposition of ECM and amplified ECM-receptor activity, which could fuel the application process of utilizing priming ITGA5 on dental clinical practice.