IL-33-expressing microvascular endothelial cells in human esophageal squamous cell carcinoma: Implications for pathological features and prognosis.

Accumulating evidence suggests that interleukin (IL)-33 plays a critical role in regulating angiogenesis and cancer progression. In this study, we characterized the pathological importance of IL-33 deployed by tumor microvascular endothelial cells (ECs) in human esophageal squamous cell carcinoma (ESCC). The expression of IL-33 in microvascular ECs in 80 cases of ESCC was examined with immunohistochemistry (IHC) and double immunofluorescence. IHC results showed that strong IL-33-immunoreactivity (IR) in microvessels, which were confirmed to be ECs by double immunofluorescence staining with IL-33/CD31 antibodies. Moreover, high proliferative activity was shown in IL-33-positive ECs, and the IL-33 functional receptor ST2 was expressed in microvascular ECs. Clinicopathological analysis revealed that IL-33-positive microvessel density (MVD) was positively correlated with node involvement in patients with ESCC. A log rank test showed a highly significant inverse correlation between the densities of IL-33-positive MVDs and overall survival rate, and patients with higher IL-33-positive MVDs tended to have a lower survival rate (both p < 0.05). Therefore, we concluded that IL-33 deployed by microvascular ECs correlates with advanced pathological features and the long-term survival rate, which provides new insights into the regulatory mechanisms of tumor angiogenesis in the tumor microenvironment and might serve as a promising target in patients with ESCC.

Tenofovir Alafenamide for Pregnant Chinese Women With Active Chronic Hepatitis B: A Multicenter Prospective Study.

BACKGROUND & AIMS: Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. METHODS: Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. RESULTS: One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. CONCLUSIONS: TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.

Sofosbuvir-based therapy for late pregnant women and infants with severe chronic hepatitis C: A case series study.

Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.

Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study.

BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

The absolute and relative changes in high-sensitivity cardiac troponin I are associated with the in-hospital mortality of patients with fulminant myocarditis.

BACKGROUND: We sought to describe the tendency and extent of high-sensitivity cardiac troponin I (hs-cTnI) changes in patients with fulminant myocarditis (FM) after admission and to explore the relationship between the in-hospital mortality of FM and the absolute and relative changes in hs-cTnI within 24 h and 48 h after admission. METHODS: In the retrospective study, the object are patients diagnosed with FM in our single centre. The value of cardiac troponin was recorded after patients admitted to hospital in succession. The absolute and relative changes in hs-cTnI within 24 h and 48 h were described as range distributions. Receiver operating characteristic (ROC) curve and Cox analyses were performed to determine the relationship between in-hospital mortality of FM and hs-cTnI changes. RESULTS: A total of 83 FM patients admitted to our centre from January 1, 2010 to December 31, 2019 were included; 69 patients survived and 14 patients died. In the survival group, 78% of patients experienced a decline in hs-cTnI within 24 h, while 36% of the mortality group exhibited a declining tendency in hs-cTnI (P = 0.003). Nearly 60% of survival group had a 0-2000 ng/l reduction in troponin from baseline within 24 h of admission. However, troponin levels of 50% of patients in the mortality group were 0-10,000 ng/ L higher than baseline 24 h after admission. Multivariable logistic analysis revealed that the declining tendency of hs-cTnI within 24 h, in addition to time from onset to admittance to hospital, intravenous immunoglobulin treatment and the abnormal level of creatinine, were associated with the in-hospital mortality of FM (for the declining tendency of hs-cTnI within 24 h, OR = 0.10, 95% CI 0.02-0.68, P = 0.018). The ROC curve revealed optimal cut-off values of - 618 ng/l for absolute change within 24 h (AUC = 0.800, P < 0.01), - 4389 ng/l for absolute change within 48 h (area under the curve = 0.711, P < 0.01), - 28.46% for relative change within 24 h (AUC = 0.810, P < 0.01), and - 52.23% for relative change within 48 h (AUC = 0.795, P < 0.01). Absolute changes and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality by Cox regression analysis after adjustment for sex, time from onset to admission, and occurrence of ventricular tachycardia or ventricular fibrillation. CONCLUSION: Most FM patients who survived experienced a decline in hs-cTnI within 24 h. The absolute and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality.

Widespread myocardial dysfunction in COVID-19 patients detected by myocardial strain imaging using 2-D speckle-tracking echocardiography.

COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<-21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (-13.7% ± 3.4% vs. -17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = -0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = -0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.

Identifying functional non-coding variants in APOA5/A4/C3/A1 gene cluster associated with coronary heart disease.

Recent genome-wide association studies identified several polymorphisms in the APOA5/A4/C3/A1 gene cluster influencing lipids level and risk of coronary heart disease (CHD). However, few studies explored the molecular mechanism. The purposes of this study were to fine-map noncoding region between APOA1 and APOC3 and then explore the clinical relevance in CHD and potential underlying mechanisms. In this study, a 2.7-kb length of the non-coding region between APOA1 and APOC3 was screened and five polymorphisms were investigated in the case-control study. The molecular mechanism was explored. Our data confirmed the association between rs7123454, rs12721030, rs10750098, and rs12721028 with CHD in 828 patients and 828 controls and replicated it in an independent population of 405 patients and 405 controls. In addition, the rs10750098 and rs12721030 are significantly associated with decreased serum APOA1 levels (P = 4.2 × 10-4 and P = 3.2 × 10-5, combined analysis), while a significant association was observed between serum APOA1 level and CHD (OR: 0.43, 95% CI: 0.28-0.64, P < .01) with adjustment for clinical covariates and different population sets. In vitro evaluation of potential function of non-coding variants between APOA1 and APOC3 demonstrated that rs10750098 as being the most sufficient to confer the haplotype-specific effect on the regulation of APOs gene transcription. Our results strongly implicate the involvement of common noncoding DNA variants in APOA5/A4/C3/A1 gene cluster in the pathogenesis of dyslipidemia and the risk of CHD.

Genetic risk scores to predict the prognosis of chronic heart failure patients in Chinese Han.

Chronic heart failure (CHF) has poor prognosis and polygenic heritability, and the genetic risk score (GRS) to predict CHF outcome has not yet been researched comprehensively. In this study, we sought to establish GRS to predict the outcomes of CHF. We re-analysed the proteomics data of failing human heart and combined them to filter the data of high-throughput sequencing in 1000 Chinese CHF cohort. Cox hazards models were used based on single nucleotide polymorphisms (SNPs) to estimate the association of GRS with the prognosis of CHF, and to analyse the difference between individual SNPs and tertiles of genetic risk. In the cohort study, GRS encompassing eight SNPs harboured in seven genes were significantly associated with the prognosis of CHF (P = 2.19 × 10-10 after adjustment). GRS was used in stratifying individuals into significantly different CHF risk, with those in the top tertiles of GRS distribution having HR of 3.68 (95% CI: 2.40-5.65 P = 2.47 × 10-10 ) compared with those in the bottom. We developed GRS and demonstrated its association with first event of heart failure endpoint. GRS might be used to stratify individuals for CHF prognostic risk and to predict the outcomes of genomic screening as a complement to conventional risk and NT-proBNP.

Bioscience learning in nursing: a cross-sectional survey of beginning nursing students in Norway.

BACKGROUND: Taking bioscience courses such as anatomy and physiology (A&P) is important for the development of nursing competence, but learning such subjects is also a challenge for many students. Nursing students' motivation, academic performance and exposure to different teaching methods may influence the learning process. METHODS: A descriptive survey was conducted with first-year nursing students at a university in Central Norway to explore their motivations, academic performance, and responses to various teaching methods used in an A&P course. RESULTS: The study provided insight into nursing students motivation, academic performance, and responses to various teaching approaches. 57 students participated in the survey and 91 % of them passed the course. The majority (61.4%) reported that classroom lecture was the most efficient and appreciated teaching method. Independent study was significantly associated with higher A&P exam grades (p-value < 0.05). CONCLUSION: The survey suggests a need for further research about the quality, and presentation of anatomy and physiology units.

[Quality grading standard of Citrus aurantium seedlings].

Forty-three annual Citrus aurantium grafted seedlings from Chongqing, Sichuan, Hunan, Jiangxi and other main producing areas were collected, and the plant height, rootstock diameter, scion diameter, root length, root diameter, lateral root number, root breadth, branch number, branch length, green leaf number, leaf length, leaf width, thorns and other indicators were measured. Through the K-cluster analysis of SPSS 19.0 software, the classification standards were obtained. Combined with the production practice, plant height, scion diameter and branch number were taken as the quality classification indexes of C. aurantium seedlings(annual grafted seedlings), and three classification standards were established. If it does not meet the three-level standard, it is unqualified seedling and cannot be used as seedling. It is suggested to use the first and second level seedlings in production.

A common variant of RIP3 promoter region is associated with poor prognosis in heart failure patients by influencing SOX17 binding.

Receptor-interacting protein kinase 3 (RIP3) is a key determinant of necroptosis and participates in ischaemia-and oxidative stress-induced necroptosis, myocardial remodelling and heart failure (HF). In this study, we tested the hypothesis that common variants in RIP3 gene were associated with the risk and prognosis of HF in the Chinese Han population. By re-sequencing and luciferase assays, we identified a common functional variant in the RIP3 promoter region. The rs3212247-T allele suppressed RIP3 promoter activity by facilitating transcription factor SOX17 binding, but not the C allele. We further recruited 2961 control participants and 3194 HF patients who underwent a mean follow-up of 19 months (6-31 months) for this study. Rs3212247 and another missense variant rs3212254 were genotyped. Although rs3212247 did not significantly associate with increased risk of HF (odds ratio = 1.00, 95% CI = 0.92-1.08, P = 0.91), it raised the risk for cardiovascular death and cardiac transplantation (hazard ratio = 1.47, 95% CI = 1.13-1.91, P = 0.004). Moreover, participants carrying the rs3212247 CC genotype had higher plasma levels of RIP3 than those carrying the TT or TC genotype (p for trend = 0.02) in New York Heart Association class III HF group. No association was found between the RIP3 missense variant rs3212254 and risk or prognosis of HF after adjustment for traditional risk factors. In conclusion, genetic variant in RIP3 promoter region is associated with increased RIP3 transcription, thus contributed to the poor prognosis of HF patients. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03461107?term=03461107&cond=Heart+Failure&cntry=CN&rank=1. Unique identifier: NCT03461107.

Comparison of Apolipoprotein B/A1 ratio, Framingham risk score and TC/HDL-c for predicting clinical outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Apolipoproteins (Apo) are known atherogenic factors that play important roles in many mechanisms related to coronary heart disease (CHD). However, it is unclear whether the apoB/apoA1 ratio is an equal or a better predictor than the Framingham Risk Score or TC/HDL-c for predicting clinical outcomes in patients undergoing percutaneous coronary intervention. METHODS: We investigated the association between Apolipoprotein B/A1 ratio and cardiovascular risk factors as well as the severity of CHD in 2256 Han Chinese patients. The potential of Apolipoprotein B/A1 ratio, Framingham Risk Score and TC/HDL-c were assessed as a marker to predict cardiovascular adverse events in a prospective subgroup of 1639 CHD patients during a 5-year follow-up. RESULTS: In the multivariate model, adjusted odds ratios (ORs) were significant for 3-VD vs. 1-VD (OR = 2.36; 95% CI: 1.65-3.38, for the fourth vs. first quartile; Ptrend < 0.001). The subgroup analysis showed that patients with a higher ApoB/ApoA1 ratio had an increased risk of developing multi-branch lesions and potentially suffer more cardiovascular adverse events (anginas, myocardial infarctions, heart failures, strokes, and cardiac deaths) in the future (adjusted HR =1.92; 95% CI: 1.10-3.13, for the fourth vs. first quartile). In the ROC analysis, the AUC for ApoB/A1 ratio was larger than that of Framingham Risk Score (0.604 vs. 0.543, p = 0.01) and TC/HDL-c (0.604 vs. 0.525, p < 0.01). CONCLUSION: Our results suggest a significant association between ApoB/ApoA1 ratio and CHD severity and cardiovascular outcomes among patients with existing CHD and ApoB/A1 ratio demonstrated a better predictive accuracy for clinical outcomes compared with Framingham Risk Score and TC/HDL-c.

miR-1322 regulates ChREBP expression via binding a 3'-UTR variant (rs1051943).

The carbohydrate response element-binding protein (ChREBP), also referred to as MLXIPL, plays a crucial role in the regulation of glucose and lipid metabolism. Existing studies have shown an association between genetic variations of the ChREBP gene and lipid levels, such as triglycerides and high-density lipoprotein cholesterol. However, mechanistic studies of this association are limited. In this study, bioinformatic analysis revealed that the polymorphism rs1051943A occurs in the complementary binding sequence of miR-1322 in the ChREBP 3'-untranslated region (UTR). Studies of potential mechanisms showed that the A allele could facilitate miR-1322 binding, and luciferase activity significantly decreased when co-transfected with a ChREBP 3'-UTR luciferase reporter vector and miR-1322 mimics in HepG2 cells. Furthermore, miR-1322 significantly regulated the expression of ChREBP downstream genes and reduced the synthesis of lipids. The expression of miR-1322 was up-regulated by glucose and palmitic acid stimulation. Population studies showed that rs1051943-A allele was only found in the Han Chinese and Uighur ethnic groups, different from European populations (G allele frequency = 0.07). In summary, we provide evidence that the rs1051943 A allele creates a functional miR-1322 binding site in ChREBP 3'-UTR and post-transcriptionally down-regulates its expression, possibly associated with levels of plasma lipids and glucose.

Identification of a novel loss-of-function mutation of the GLA gene in a Chinese Han family with Fabry disease.

BACKGROUND: Fabry disease is an X-linked recessive lysosomal disorder caused by deficient enzymatic activity of α-galactosidase A (α-Gal A). The insufficient enzymatic activity leads to excessive accumulation of glycosphingolipids, the substrates of the enzyme, in lysosomes in organs and tissues. Mutations in the α-Gal A gene (GLA, Xq22) have been proven to be responsible for Fabry disease. METHODS: In this study, we report a four-generation pedigree with left ventricular hypertrophy and chronic renal failure that was diagnosed by sequencing the GLA gene. An over expression system was constructed to evaluate the function of the detected mutation. RESULTS: We identified a novel mutation in exon 6 of the GLA gene, p.Asn278Lys, which completely co-segregated with the disease phenotype. The protein level of α-Gal A was significantly lower in the variant group than in the wild-type group; additionally, the pharmacological chaperone 1-deoxy-galactonojirimycin (DGJ) effectively normalized the enzyme activity of α-Gal A and its decline at the protein level. CONCLUSIONS: This study is the first to report a novel loss-of-function mutation, p.Asn278Lys, in exon 6 of the GLA gene as a genetic aetiology for Fabry disease. In addition, we analysed the feasibility of DGJ as a therapeutic approach for this particular GLA mutation.

Cellular and clinicopathological features of the IL-33/ST2 axis in human esophageal squamous cell carcinomas.

BACKGROUND: Emerging evidence has suggested that interleukin (IL)-33 and its primary functional receptor ST2 are involved in the pathogenesis of tumorigenesis. METHODS: Using immunohistochemistry (IHC) and double immunofluorescence staining, we characterized the cellular and clinicopathological features of the IL-33/ST2 axis in different compartments in human esophageal squamous cell carcinoma (ESCC) surgical specimens. RESULTS: IHC data revealed an increased expression of IL-33-immunoreactivity (IR) and ST2-IR located in both ESCC cells and tumor stromal cells; which were associated with advanced clinicopathological features such as TNM stages and node involvement. However, the Kaplan-Meier analysis showed that densities of neither IL-33 positive nor ST2 positive cells in both the ESCC mass and stroma were associated with the overall survival rate in patients with ESCC. Double immunofluorescence staining for cellular feature analysis demonstrated that these IL-33 positive and ST2 positive cells in ESCCs were with a high proliferation rate, and IL-33-IR was frequently co-expressed with ST2-IR in both ESCC and stromal cells. CONCLUSION: Significant altered cellular features of the IL-33/ST2 axis in ESCCs were associated with advanced clinicopathological variables. The data suggest that the IL-33/ST2 axis might be involved in the progression of human ESCCs.

Analysis of codon usage bias in the VP1 gene of the human norovirus GII.2 genotype.

To investigate the codon usage patterns of all available VP1 gene sequences of the GII.2 genotype, to determine the factors that affect these patterns, and to provide comprehensive details of the characteristics and evolution of the gene. Complete 519 sequences of VP1 gene of the HuNoV GII.2 genotype with known sampling dates and geographic locations from 1971 - 2017 were retrieved from the GenBank nucleotide database of the National Center for Biotechnology Information (NCBI) and analyzed. The percentage composition of T, C, A, and G nucleotides were 24.80 ± 0.30, 26.61 ± 0.31, 25.84 ± 0.13, and 22.75 ± 0.17 %, respectively, with C and A relatively more abundant than T and G, and C the most abundant (p < 0.0001). The values of T3s (34.10 ± 0.90 %) and C3s (33.54 ± 0.90 %) were significantly higher than those of A3s (29.98 ± 0.43 %) and G3s (24.13 ± 0.51 %) (p < 0.0001). While T3s was highest among the four nucleotides, G3s was the lowest. Among the 18 most frequently employed synonymous codons, six optional codons ended with T, five ended with C, five ended with A and two ended with G. Codons ending with T were the most frequently used. The ENC ranged from 51.90 to 54.25 (mean = 52.38 ± 0.43) among the 519 VP1 gene sequences. There were significant correlations between ENC and C % and G % (p < 0.01). Codons containing CpG (1 and 2 or 2 and 3 codon positions) showed the lowest frequencies, while 30, 29, and 2 codons were above, below and on the mean line, respectively. The first four principal components accounted for 69.11 % of the total variation, with the first, second, third, and fourth principal axes contributing 37.90, 14.83, 9.61, and 6.77 %, respectively. The strains were not clustered by country of isolation or year of sampling. Gravy were significantly correlated with T3s, C3s, G3s, GC3s, and ENC (p < 0.01). Mutation pressure and natural selection contributed to the codon usage bias of the VP1 gene of the HuNoV GII.2 genotype. There was a correlation between GC12s and GC3s (R2 = 0.032; p < 0.0001). The relative neutrality was 3.20 %, while natural selection was 96.80 %. The VP1 gene exhibits low codon usage bias which is affected primarily by natural selection, followed by mutation pressure and translational selection.

Increased expression of interleukin-21 along colorectal adenoma-carcinoma sequence and its predicating significance in patients with sporadic colorectal cancer.

The role and significance of interleukin (IL)-21 in the development of sporadic CRC have not been well defined. The aim of this study is therefore to investigate the dynamics of the IL-21 along colorectal adenoma-carcinoma sequence and to evaluate the impact of IL-21 on clinicopathological parameters and CRC prognosis. The real-time PCR results showed that the level of IL-21 in adenomas (n=50) and sporadic CRC (n=50) were significantly higher than that in normal controls (n=18), which were predominately observed in the adenoma/CRC stroma. Analysis revealed that IL-21 level was correlated with the overall survival time in CRC patients. Double immunofluorescence observations confirmed that IL-21 positive cells were mostly natural killer cells and T lymphocytes in the tumor stroma. These results indicate that significant increased IL-21 expression present within the adenoma/CRC microenvironment might have a potential predicating significance for survival time in patients with CRC.

[Study on associated plants and spatial distribution pattern of Dipsacus asperoides populations].

In order to understand the associated species and the population distribution pattern, the investigation of 32 sample plotsfrom the main natural distribution area in Dipsacus asperoides community was carried by quadrat method .The results showed that there were 156 species, which belong to 131 genera and 60 families. There were more species in the two dominant families, Asteraceae and Rosaceae. There were many types of associated, but most appeared at a low frequency. The vegetation type were mostly herbaceous and shrub species, which accounted for 77.6% of the total species. The value of t was greater than t0.05 by methods of variance/mean, showed the difference was significant and the distribution pattern of D. asperoides were cluster distribution. The determination results of seven aggregation intensity index also showed that D. asperoides population accorded with the characteristics of cluster distribution（C>1，K>0，Ca>0，m*>1，m*/m>1，I>0，GI>0）.