Objective To explore the expression of frizzled-7 and β-catenin proteins in hepatocellular carcinoma (HCC),and determine their relationship with clinicopathological features and prognosis.Methods Expression levels of frizzled-7 and β-catenin proteins were detected by the SP immunohistochemical technique in 64 cases of HCC and 15 normal liver tissues.Results Frizzled-7 and β-catenin proteins were found in 42 (65.6％) and 45 (70.3％) of tumor specimens respectively,which was significantly higher than that in normal liver tissues.The expression of frizzled-7 protein was significantly positively correlated with that of β-catenin (P ＜ 0.05) in HCC.The high expression of frizzled-7 was closely correlated to tumor size (P =0.014),histologic grade (P =0.020),portal vein tumor thrombus (P =0.034),tumor recurrence (2 years,P =0.030),TNM stage (P =0.022),and HBsAg (P =0.025),and negatively correlated with 5-year postoperative survival (47.6％ vs.13.2％).The expression of β-catenin protein was significantly associated with histologic grade (P =0.012),tumor recurrence (2 years,P =0.010),and TNM stage (P =0.026),and negatively correlated with 5-year postoperative survival (36.8％ vs.20.0％).Conclusions Frizzled-7 is overexpressed in HCC and associated with decreased postoperative survival.Moreover,frizzled-7 may up-regulate the expression of β-catenin and promote β-catenin-mediated tumor invasion and recurrence.

Objective To assess the preferential expressions of peripheral blood T cell receptor beta chain variable region (TRBV) subfamilies in patients with psoriasis vulgaris(PV), and to estimate their role in the pathogenesis of psoriasis. Methods Thirty-three upstream primers were designed to target the human functional TRBV genes, downstream primers to target the common T cell receptor beta constant (TRBC) gene,with T cell receptor alpha constant (TRAC) gene as the internal reference. Total RNA was extracted from the peripheral blood T cells of 10 health human controls and 10 patients with PV, and transcribed into cDNA.Then, TRBV genes were amplified by real-time fluorescence quantitative PCR (RFQ-PCR) and the fluorescence intensity of each samples was detected. The expression levels of TRBV genes in the control group were used to calculate the cut-off values (mean expression levels of TRBV subfamilies in the 10 normal controls + 3 standard deviations). When the expression level of a TRBV subfamily from patients with PV was equal to or higher than the cut-off value, it was considered as the preferentially expressed TRBV subfamily. Results The threshold cycle (Ct) value varied from 21 to 24 for TRAC gene. The difference in the Ct value between TRBV subfamily genes and TRAC gene in patients with PV was 2.98 for TRBV2 gene, 3.24 for TRBV5-7 gene, 2.52 for TRBV6-6/6-9 gene, 2.04 for TRBV 12 gene, 3.56 for TRBV 24 gene, and 4.12 for TRBV 29 gene, and the expression levels of these subfamily genes were significantly higher than those in the normal controls (all P ＜ 0.05). According to the above standard, TRBV6-6/6-9, TRBV12 and TRBV29 were considered to be preferentially expressed subfamilies. Conclusions There is a preferential expression of TRBV gene subfamilies in peripheral blood of patients with psoriasis vulgaris, which may play a vital role in the abnormal T cell-mediated immune responses in psoriasis.

Objective To investigate the effect of comprehensive management mode intervention in elderly patients with moderate/severe chronic obstructive pulmonary disease at stable stage. Methods A total of 150 elderly patients with stable-stage COPD were randomly divided into two groups, 75 in each group. The control group received routine medication, while the observation group was given comprehensive management mode intervention, including health education,rational medication, pulmonary rehabilitation training and psychological guidance. Both groups were treated for 12 months. Differences in lung function parameters, modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), 6-minute walk test (6MWT), and frequency of acute exacerbation of COPD (AECOPD) were compared between the two groups. Results: After treatment, FEV1/FVC and FEV1%pred of observation group（57.65±11.62%、61.83±13.50%）were higher than control group（52.38±13.24%、53.42±13.93%）(P<0.05), the mMRC and CAT scores of the observation group were decreased (P<0.05), and the 6MWT was increased (P<0.05), but no significant differences in the control group (P>0.05). Within 12 months of treatment, the frequency of AECOPD in the observation group was less than that in the control group (P<0.05). Conclusions: In the treatment of elderly patients with moderate/severe chronic obstructive pulmonary disease, comprehensive management mode intervention can help delay the deterioration of lung function, correct the difficulty of breathing, improve the quality of life, and reduce the number of AECOPD.

HOXD-AS1 is a recently discovered pivotal cancer-related long non-coding RNA(lncRNA) .Abnormal expression of HOXD-AS1 exhibits a regulatory role in the occurrence and development of tumors,and is expected to become a new tumor marker.Clarifying the mechanism of HOXD-AS1 will provide a feasible theoretical basis and potential intervention targets for the diagnosis and treatment of tumors.This article reviews the current research status of HOXD-AS1 in tumors.

Colon cancer associated transcript 2 (CCAT2) is found recently an important member of cancer-related long non-coding RNA (lncRNA).Dysregulation of CCAT2 plays a pivotal role in tumor pathophysiological processes,especially in tumourigenesis and progression of digestive system neoplasms,thus,CCAT2 likely represents a novel cancer biomarker or therapeutic target.Elucidation of the molecular mechanisms of CCAT2 will provide a feasible theoretical basis and potential interventional target for the diagnosis and treatment of malignancies.The present review summarizes current evidences of CCAT2 in digestive system neoplasms.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment