Colorectal image analysis for polyp diagnosis.

Colorectal polyp is an important early manifestation of colorectal cancer, which is significant for the prevention of colorectal cancer. Despite timely detection and manual intervention of colorectal polyps can reduce their chances of becoming cancerous, most existing methods ignore the uncertainties and location problems of polyps, causing a degradation in detection performance. To address these problems, in this paper, we propose a novel colorectal image analysis method for polyp diagnosis via PAM-Net. Specifically, a parallel attention module is designed to enhance the analysis of colorectal polyp images for improving the certainties of polyps. In addition, our method introduces the GWD loss to enhance the accuracy of polyp diagnosis from the perspective of polyp location. Extensive experimental results demonstrate the effectiveness of the proposed method compared with the SOTA baselines. This study enhances the performance of polyp detection accuracy and contributes to polyp detection in clinical medicine.

Antigen clearance at the peak of the primary immune response induces experimental autoimmune encephalomyelitis.

Autoimmune demyelinating diseases can be induced by an immune response against myelin peptides; however, the exact mechanism underlying the development of such diseases remains unclear. In experimental autoimmune encephalomyelitis, we found that the clearance of exogenous myelin antigen at the peak of the primary immune response is key to the pathogenesis of the disease. The generation of effector T cells requires continuous antigen stimulation, whereas redundant antigen traps and exhausts effector T cells in the periphery, which induces resistance to the disease. Moreover, insufficient antigenic stimulation fails to induce disease efficiently owing to insufficient numbers of effector T cells. When myelin antigen is entirely cleared, the number of effector T cells reaches a peak, which facilitates infiltration of more effector T cells into the central nervous system. The peripheral antigen clearance initiates the first wave of effector T cell entry into the central nervous system and induces chronic inflammation. The inflamed central nervous system recruits the second wave of effector T cells that worsen inflammation, resulting in loss of self-tolerance. These findings provide new insights into the mechanism underlying the development of autoimmune demyelinating diseases, which may potentially impact future treatments.

Obesity accelerates immune evasion of non-small cell lung carcinoma via TFEB-dependent upregulation of Siglec-15 and glycolytic reprogramming.

Although obesity contributes to tumor incidence and progression in various cancers, whether obesity impacts the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) remains largely under-explored. We generated NSCLC xenograft model in diet-induced obese mice and identified that TFEB is critical to accelerate obesity-related NSCLC progression with mimic intrinsic functions on tumor biology. Mechanically, TFEB binds directly to Siglec-15 promoter to upregulate Siglec-15 expression and binds to Hk2 and Ldha promoters to enhance glycolytic flux in NSCLC cells, which restrain the expansion and cytotoxic function of CD8+ T cells while maintain suppressive Treg cells in TME, jointly promoting immune evasion of NSCLC cells in obesity. Blocking tumor TFEB improves the therapeutic efficiency of anti-PD-1 in obese mice. Altogether, our data identify essential roles of TFEB in remodeling immunosuppressive TME and promoting NSCLC development in obesity, providing scientific rational for TFEB as a potential biomarker to predict immune checkpoint blockade efficiency in obese NSCLC patients.

LncRNA HCG11 Facilitates Nasopharyngeal Carcinoma Progression Through Regulating miRNA-490-3p/MAP3K9 Axis.

Purpose: Long noncoding RNAs (LncRNAs) play complex but important roles in the progression of various tumors. This study aimed to elucidate the functional mechanisms of the HLA complex group 11 (HCG11) in nasopharyngeal carcinoma (NPC). Patients and Methods: HCG11 levels in NPC specimens were determined by fluorescence in situ hybridization (FISH) and qPCR. Proliferation, apoptosis, and metastasis of NPC cells were determined using CCK8, colony formation, annexin V-PI, and transwell assays. A murine tumor xenograft model was used to investigate the regulatory function of HCG11 in NPC in vivo, and immunohistochemical staining was used to determine the Ki-67 level in tumors. The target relationships between HCG11, microRNA miR-490-3p, and MAPK kinase kinase 9 (MAP3K9) were detected using bioinformatics, qPCR, western blotting, and luciferase reporter assays. Results: HCG11 was highly expressed in NPC tissues and was positively associated with tumor stage, lymphatic metastasis, and poor prognosis. Functionally, HCG11 knockdown inhibited proliferation and migration and induced apoptosis of NPC cells. Mechanistically, miR-490-3p is a direct target of HCG11, oncogenic functions of HCG11 in NPC cell proliferation and migration can be partially reversed by the miR-490-3p inhibitor. HCG11 significantly increased mitogen-activated protein kinase MAPK kinase 9 (MAP3K9) levels by inhibiting miR-490-3p. Conclusion: HCG11 facilitates NPC progression via MAP3K9 signaling by sponging miRNA-490-3p, which may contribute to new prognostic markers and promising therapeutic targets.

The role of IDO, IL-10, and TGF-ß in the HCV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Indoleamine-2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan to kynurenine and studies have revealed that IDO play a vital role in regulation of liver immunity and inflammation activities. This study investigated the association between plasma IDO and disease severity and the possible marker role of IDO in the inflammatory process of hepatitis C. In this study, 80 individuals with HCV infection were retrospectively selected. Plasma levels of IDO, IL-10, and TGF-ß were assayed by ELISA. Clinical characteristics of patients, including the levels of ALT, AST, and total bilirubin (TBil) were collected from clinical databases. HCV-related liver cirrhosis (HC-Cirr) and HCV-related Hepatocellular carcinoma (HCV-HCC) had significantly high plasma levels of IDO compared to other patient groups and healthy controls. Plasma IL-10 level were significantly greater in all chronic liver disease groups and with respect to TGF-ß, the level was high in all the selected patients with HCV infection compare with controls. Moreover, HCV-HCC patients showed highest values for both IL-10 and TGF-ß, with significant difference compared with other groups. In addition, plasma IDO was positively correlated with TGF-ß among all patients with HCV infection (r = 0.4509, P < 0.0001), with IL-10 in CHC patients (r = 0.4787, P = 0.0047), with TBil in HCV-Cirr patients (r = 0.4671; P = 0.0093). High level of IDO and TGF-ß is associated with hepatocyte necrosis and intrahepatic inflammation, and may be used as an index of disease progression for patients with chronic HCV infection.

Prognostic value of Systemic immune-inflammation index in cancer: A meta-analysis.

Systemic immune-inflammation index (SII), on the basis of lymphocyte, neutrophil and platelet counts had been published to be a good prognostic factor in multiple cancers. Nevertheless, the prognostic value of SII in cancer patients remains inconsistent. Therefore, we carried out a meta-analysis to evaluate the prognostic value of SII in these patients with cancer. A total of 22 articles with 7657 patients enrolled in this meta-analysis. The combined result revealed that a high SII was evidently correlated with poor overall survival (OS) (HR=1.69, 95%CI=1.42-2.01, p<0.001), poor time to recurrent (TTR) (HR=1.87, p<0.001) , poor progress-free survival (PFS) (HR=1.61, p=0.012) ,poor cancer-specific survival (CSS) (HR=1.44, p=0.027) , poor relapse-free survival (RFS) (HR=1.66, p=0.025) and poor disease-free survival (DFS) (HR=2.70, p<0.001) in patients with cancers. Subgroup analysis indicated that SII over the cutoff value could predict worse overall survival in Hepatocellular carcinoma (p<0.001), Gastric cancer (p=0.005), Esophageal Squamous Cell Carcinoma (p=0.013), Urinary system cancer (p<0.001), Small cell lung cancer (p<0.001), Non-Small cell lung cancer (p<0.001) and Acral Melanoma (p<0.001). The largest effect size was observed in the Hepatocellular carcinoma (HR=2.11). In addition, these associations did not vary significantly by the cutoff value, sample size and ethnicity. Therefore, high SII may be a potential prognostic marker in patients with various cancers and associated with the poor overall outcomes.

Determinant roles of gender and age on SII, PLR, NLR, LMR and MLR and their reference intervals defining in Henan, China: A posteriori and big-data-based.

OBJECTIVES: By now, there are few data of the reference intervals (RIs) of SII, PLR, NLR, LMR and MLR. We aimed to establish RIs of SII, PLR, NLR, LMR and MLR for healthy persons. METHODS: A retrospective analysis on a cohort of ostensibly healthy, aged no <18 years old physical examinees who took health examination from January to December in 2013 was conducted to explore influences of age and gender on SII, PLR, NLR, LMR and MLR and to establish their RIs. And another cohort of 450 persons in our hospital from January to July in 2016 is included for validations of RIs. RESULTS: NLR, LMR and MLR were significantly different between gender groups (P=.010; P<.001; P<.001, separately), while SII and PLR were not (P=.137; P=.267, separately). While SII was not changed much between age groups (P=.842), PLR, NLR, LMR and MLR were significantly different (all with P<.001). RIs of SII, PLR, NLR, LMR and MLR were: SII: [161,701]; PLR: 18-65 year-old: [61,179]/>65 year-old: [55,179]; NLR: 18-65 year-old male: [0.90,2.94]/18-65 year-old female: [0.85,3.06]/>65 year-old male: [0.95,3.57]/aged >65 year-old female: [0.83,3.30]; LMR: 18-65 year-old male: [2.50,7.50]/18-65 year-old female: [2.75,8.50]/>65 year-old male: [2.16,7.41]/>65 year-old female: [2.40,8.33]; MLR: 18-65 year-old male: [0.12,0.35]/18-65 year-old female: [0.10,0.32]/>65 year-old male: [0.12,0.41]/>65 year-old male: [0.11,0.33]. CONCLUSIONS: RIs of SII, PLR, NLR, LMR and MLR of people in central China were established and validated. It will benefit experimental design of the related studies and lead to better standardizations of SII, PLR, NLR, LMR and MLR for their clinical applications.

Diagnostic value of autoantibodies combined detection for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disease, there are many autoantibodies produced during disease progression in the patients' serum, and this work is to select a best detection scheme for RA diagnosis. METHODS: Autoantibody levels including rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), mutated citrullinated vimentin (MCV), anti-keratin antibodies(AKA), anti-perinuclear factor (APF), and Ig heavy chain binding protein (BIP), were measured, and the sensitivity, specificity, predictive values, accuracy, and Youden's index of different combining forms were all calculated in RA patients, disease, and healthy control group. The differences in the positive rates of the three groups were compared between any two of them. RESULTS: Generally speaking, the sensitivity of the autoantibodies detected in parallel combination was higher than that in tandem, which was more specific. The sensitivity of anti-MCV and RF calculated in parallel (87.61%) was obviously better than that of anyone autoantibody (P<.05), and only increased slightly even if more autoantibodies were tested in parallel (P>.05). The specificity of anti-CCP and BIP measured in tandem (95.92%) was obviously higher than that of anyone autoantibody (P<.05). While increasing the detected number of autoantibody from two kinds to three or more, the specificity was improved insignificantly (P>.05). CONCLUSION: Anti-BIP and CCP antibodies detected in tandem combination can obtain higher specificity, and have good clinical value for the differential diagnosis of RA.

Antigen-oriented T cell migration contributes to myelin peptide induced-EAE and immune tolerance.

Treatment with soluble myelin peptide can efficiently and specifically induce tolerance to demyelination autoimmune diseases including multiple sclerosis, however the mechanism underlying this therapeutic effect remains to be elucidated. In actively induced mouse model of experimental autoimmune encephalomyelitis (EAE) we analyzed T cell and innate immune cell responses in the central nervous system (CNS) and spleen after intraperitoneal (i.p.) infusion of myelin oligodendrocyte glycoprotein (MOG). We found that i.p. MOG infusion blocked effector T cell recruitment to the CNS and protected mice from EAE and lymphoid organ atrophy. Innate immune CD11b(+) cells preferentially recruited MOG-specific effector T cells, particularly when activated to become competent antigen presenting cells (APCs). During EAE development, mature APCs were enriched in the CNS rather than in the spleen, attracting effector T cells to the CNS. Increased myelin antigen exposure induced CNS-APC maturation, recruiting additional effector T cells to the CNS, causing symptoms of disease. MOG triggered functional maturation of splenic APCs. MOG presenting APCs interacted with MOG-specific T cells in the spleen, aggregating to cluster around CD11b(+) cells, and were trapped in the periphery. This process was MHC II dependent as an MHC II directed antibody blocked CD4(+) T cell cluster formation. These findings highlight the role of myelin peptide-loaded APCs in myelin peptide-induced EAE and immune tolerance.

The platelet-to-lymphocyte ratio, superior to the neutrophil-to-lymphocyte ratio, correlates with hepatitis C virus infection.

OBJECTIVES: The platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been studied widely in cancer diseases. However, their correlation with hepatitis C virus (HCV) infection is unknown. The aim of this study was to investigate the correlation of PLR and NLR with disease severity in patients with HCV-related liver disease and the virological response in chronic hepatitis C (CHC) patients. METHODS: The clinical data of 120 HCV-infected patients and 40 healthy controls were analyzed. The clinical data of 24 CHC patients who had been followed up regularly were collected for the following time points: before treatment (week 0) and weeks 4, 48, and 72 during treatment. These data were also analyzed. All data were collected from the database of the hospital patient electronic medical record system. RESULTS: The HCV-related cirrhosis group and HCV-related hepatocellular carcinoma group were found to have lower PLRs (61±31 and 51±23) than the healthy controls (115±23). The PLR of the HCV cleared group (154±85) was significantly higher than that of the HCV untreated group and HCV uncleared group (90±28 and 88±40, respectively). Receiver operating characteristics curve analysis for the PLR showed an area under the curve of 0.772 (95% confidence interval 0.674-0.869, p<0.000); for NLR, the area under the curve was 0.612 (95% confidence interval 0.495-0.730, p=0.063). Furthermore, an increasing PLR in CHC patients indicated a good virological response, and a stable PLR or a downward trend in PLR could predict no rapid virological response being achieved by week 4, and even no sustained virological response by week 72. CONCLUSIONS: The PLR is closely related to disease severity in patients with HCV-related liver disease and to the virological response in CHC patients. Dynamic continuous monitoring of the PLR will contribute to disease surveillance, with an increasing tendency predicting a good virological response.

Predictive value of circulating miR-328 and miR-134 for acute myocardial infarction.

MicroRNA (miRNAs) is demonstrated to be present in the blood of humans and has been increasingly suggested as a novel biomarker for various pathological processes in the heart, including myocardial infarction, myocardial remodeling and progression to heart failure. In this study, we aim to evaluate the diagnostic and prognostic value of circulating miR-328 and miR-134 in patients with acute myocardial infarction (AMI). Circulating levels of miR-328 and miR-134 were detected by quantitative real-time PCR in plasma samples from 359 AMI patients and 30 healthy volunteers. Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) were measured using electrochemiluminescence-based methods. MiRNAs were assessed for discrimination of a clinical diagnosis of AMI and for association with primary clinical endpoint defined as a composite of cardiogenic death and development of heart failure within 6 months after infarction. Results showed that levels of plasma miR-328 and miR-134 were significantly higher in AMI patients than in healthy controls. Receiver operating characteristic curve analyses showed significant diagnostic value of miR-328 and miR-134 for AMI. However, neither of them was superior to hs-cTnT for the diagnosis. Additionally, increased miRNA levels were strongly associated with increased risk of mortality or heart failure within 6 months for miR-328 (OR 7.35, 95 % confidence interval 1.07-17.83, P < 0.001) and miR-134 (OR 2.28, 95 % confidence interval 1.03-11.32 P < 0.001). In conclusion, circulating miR-328 and miR-134 could be potential indicators for AMI, and the miRNA levels are associated with increased risk of mortality or development of heart failure.

Circulating miR-208b and miR-34a are associated with left ventricular remodeling after acute myocardial infarction.

Left ventricular remodeling after acute myocardial infarction (AMI) is associated with adverse prognosis. It is becoming increasingly clear that circulating miRNAs could be promising biomarkers for various pathological processes in the heart, including myocardial infarction, myocardial remodeling and progression to heart failure. In the present study, a total of 359 consecutive patients were recruited. Plasma samples were collected on admission. Echocardiographic studies were performed during the admission and at six months follow-up after AMI. Remodeling was defined as an at least 10% increase from baseline in the left ventricular end-diastolic volume. Plasma miRNA levels were assessed for association with six months mortality or development of heart failure. Results showed that levels of plasma miR-208b and miR-34a were significantly higher in patients with remodeling than those without. Increased miRNA levels were strongly associated with increased risk of mortality or heart failure within six months for miR-208b (OR 17.91, 95% confidence interval=2.07-98.81, p=0.003), miR-34a (OR 4.18, 95% confidence interval=1.36-12.83, p=0.012) and combination of the two miRNAs (OR 18.73, 95% confidence interval=1.96-101.23, p=0.000). The two miRNA panels reclassified a significant proportion of patients with a net reclassification improvement of 11.7% (p=0.025) and an integrated discrimination improvement of 7.7% (p=0.002). These results demonstrated that circulating miR-208b and miR-34a could be useful biomarkers for predicting left ventricular remodeling after AMI, and the miRNA levels are associated with increased risk of mortality or heart failure.

[Application of mycobacterial interspersed repetitive units in typing Mycobacterium tuberculosis in Shandong].

OBJECTIVE: To evaluate the application of mycobacterial interspersed repetitive units (MIRU) in typing Mycobacterium tuberculosis in Shandong. METHOD: 826 strains of M. tuberculosis from laboratories of 12 county tuberculosis dispensaries in Shandong were cultured and typed by MIRU genotyping in the KICID laboratory. RESULTS: The 826 strains were typed to 201 distinct MIRU patterns, and 123 isolates were unique, 703 strains were grouped into 1 of 78 different MIRU clusters, and the MIRU genotype of the largest cluster was 223325173533. Among the clustered strains, 18 patients had an epidemiological history of contact. The Hunter-Gaston discriminatory index was 0.90. The allelic diversity of the sample was calculated for each other of the MIRU loci, and showed that MIRU26 had 10 alleles and was highly discriminative, while other five MIRU loci (MIRU31, 10, 39, 40, 4) were moderately discriminative. The reproducibility of the MIRU method was 100%. It took about RMB yen50 to genotype one strain. CONCLUSIONS: MIRU genotyping is a reproducible, fast, simple, and relatively cheap method. But because the isolates of 223325173533 genotype are predominant (30.89% of the isolates) in Shandong Province, it needs a second method IS6110 RFLP or by adding other more discriminative variable-number tandem repeat (VNTR) loci to improve the discriminative power.