[Colorectal cancer with ß-catenin protein expression deficiency: a clinicopathological analysis].

Objective: To investigate the clinicopathological features and molecular characteristics of ß-catenin-deficient colorectal cancer. Methods: The clinical, pathological and molecular features of 11 colorectal cancers with ß-catenin protein loss diagnosed at the 960th Hospital of People's Liberation Army of China, from January 2012 to November 2022 were analyzed. Results: Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. ß-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of ß-catenin protein expression. Conclusion: ß-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

[Association of circulating levels of soluble PD-1, PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma].

Objective: To investigate the association of circulating sPD-1 level and PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma. Methods: A case-control study was conducted. A total of 237 chronic HBV infection cases and 138 HBV infection-associated hepatocellular carcinoma in the Department of Infectious Diseases of the First Hospital of Shanxi Medical University from 2018 to 2021 were selected as the case group. About 250 individuals who visited a hospital physical examination center for routine physical examination during the same period were selected as the control group. Plasma sPD-1 levels were measured by using an ELISA kit and genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The association of sPD-1 levels and PD-1 polymorphisms with HBV infection as well as HBV infection-associated hepatocellular carcinoma was analyzed by using logistic regression models after adjusting for age, sex, alcohol consumption, smoking, ALT and AST levels. The sPD-1 level and PD-1 polymorphisms were independent variables, and HBV infection was the dependent variable. Results: The age of 237 chronic HBV infections, 138 HBV infection-related liver cancer case subjects and 250 control subjects in the study was (49.1±10.8), (51.9±12.7) and (50.7±11.9) years, respectively. Multivariate logistic regression model analysis showed that with a 1 pg/ml increase in sPD-1 level, the OR (95%CI) values for the risk of incident HBV infection cases and HBV hepatocellular carcinoma cases were 1.92 (1.68-2.19) and 2.02 (1.69-2.40). For rs2227981, compared with the CC genotype, the TT genotype had a lower risk of HBV infection and liver cancer associated with HBV infection, with OR (95%CI) values of 0.45 (0.22-0.91) and 0.35 (0.14-0.91). For rs2227982, compared with the CC genotype, the CT and TT genotypes also had a lower risk of HBV infection [OR (95%CI) values of 0.72 (0.53-0.97) and 0.57 (0.35-0.93)] and HBV infection-related liver cancer [OR (95%CI) values of 0.64 (0.45-0.92) and 0.52 (0.29-0.93)]. Conclusions: Plasma sPD-1 levels and PD-1 gene polymorphisms are associated with HBV infection and HBV infection-associated hepatocellular carcinoma.

Effect of iguratimod and methotrexate on RANKL and OPG expression in serum and IL-1ß-induced fibroblast-like synoviocytes from patients with rheumatoid arthritis.

The receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK)/osteoprotegerin (OPG) system plays a key role in rheumatoid arthritis (RA)-associated bone erosion. The upregulation of the RANKL/OPG ratio promotes bone erosion. The objective of this study is to explore the effects of iguratimod, a small-molecule disease-modifying antirheumatic drug (DMARD), alone or in combination with methotrexate (MTX), on RANKL and OPG expression in RA. We performed an enzyme-linked immunosorbent assay (ELISA) to investigate the modulatory effects of iguratimod, MTX, or their combination on serum RANKL and OPG levels of patients with RA before and after treatment for 12 and 24 weeks. Furthermore, fibroblast-like synoviocytes (FLS) from patients with RA were interleukin (IL)-1ß-stimulated and then treated with different concentrations of iguratimod, MTX, or both, and RANKL and OPG expressions were investigated by using ELISA, quantitative real-time polymerase chain reaction (qPCR) and western blot analysis. We found that RANKL levels and the RANKL/OPG ratio significantly decreased in both serum and IL-1ß-induced RA FLS after treatment. Moreover, combination therapy with iguratimod and MTX showed an even stronger inhibition than each drug alone did. Our results suggest that iguratimod and MTX, especially in combination, efficaciously protected against bone erosion by suppressing the production of RANKL.

Meta-analytical association between angiotensin-converting enzyme gene polymorphisms and sarcoidosis risk.

Previous reports identified an association between sarcoidosis and an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme. Our meta-analysis of articles published between March 1996 and June 2013 identified studies in the PubMed, EMBASE, and the China National Knowledge Infrastructure databases. We examined whether angiotensin-converting enzyme polymorphisms influence sarcoidosis susceptibility. The strength of the association between I/D polymorphisms and sarcoidosis risk was measured based on the odds ratio and 95% confidence interval. Analysis was based on recessive and dominant models. Ethnic subgroup analysis from 18 articles (1882 cases and 3066 controls) showed that DD homozygote carriers were at a slightly increased risk of sarcoidosis compared with II homozygotes and DI heterozygotes (P = 0.03). Comparison of DD plus DI vs II revealed no significant association with sarcoidosis in group and ethnic subgroup analysis. We found that the I/D polymorphism in the angiotensin-converting enzyme gene was not associated with a major risk of sarcoidosis.

LL-37 expression in the skin in systemic lupus erythematosus.

The objective of this study was to investigate the expression and relationship of LL-37, plasmacytoid dendritic cells (pDCs) and interferon-alpha (IFN-α) in skin in systemic lupus erythematosus (SLE), and their role in SLE pathogenesis. Skin biopsies were taken from nine SLE patients and six healthy volunteers. Expression of LL-37, pDCs and IFN-α in skin specimens and consecutive sections of skin was detected with an immunohistochemical technique (IH); the expression of LL-37 and pDCs in the samples was detected with in situ hybridization (ISH). The expression levels of LL-37, pDCs and IFN-α were significantly higher in SLE skin than in that of healthy controls (p < 0.001) with either the IH or the ISH technique, and the location of positive expression in consecutive sections was similar. Correlation analysis showed that the expression levels of LL-37, pDCs and IFN-α correlated positively with each other. In conclusion, the expression of LL-37, pDCs and IFN-α was increased in the skin of patients with active SLE. It is necessary to study further the role of LL-37 in the pathogenesis of SLE, and the exact relationship among LL-37, pDCs and IFN-α.

[The effect of trichosanthin on immunoregulatory T lymphocytes].

The effect of trichosanthin (TCS) on immune system has drawn attentions of the investigators both at home and abroad. The purpose of this study is to evaluate the prospects of TCS on autoimmune diseases and immunodeficiency diseases by detecting the immunoregulatory T lymphocytes (T8, 2H4, 4B4) count and cellular DNA content under the influence of TCS with flow cytometer using indirect immunofluorescence technique and lymphocyte culture in normal subjects and systemic lupus erythematosus patients. The results showed that the percentage of T8+ cells decreased, 4B4+ cells increased, 2H4+ cells did not markedly change after adding TCS. The raise of DNA content in S stage was dose-dependent to TCS, especially in large doses. It is concluded that TCS could selectively inhibit T8+ cells and could obviously increase the number of 4B4+ cells. It is suggested that TCS could enhance humoral immunity through the ratio of immunoregulatory T cells. So TCS might help immunodeficiency patients such as AIDS to reestablish their immune system.

[Lymphocyte phenotypes and their correlation with clinical features in systemic lupus erythematosus (SLE)].

Lymphocyte phenotypes of peripheral blood from 32 SLE patients and 30 normal subjects were studied with 13 kinds of monoclonal antibodies using indirect immunofluorescence technique. The results showed that T4+, T8+, T3+ and T11+ cells decreased in active cases of SLE, while Ia+, IL2R1+ and PCA-1+ cells increased, other B-cell phenotypes (B1, B2, B4, IgM, IgG, IgD) showed no significant difference from those of the normal group. Thus, in inactive SLE after therapeutic management, the numbers of T3+, T11+, T4+, Ia+ and IL2R1+ cells no longer show any abnormality, but the numbers of T8+, PCA-1+ cells and the level of serum IgG are still higher than normal. From the above-mentioned results, it was shown that: 1. The key change in active SLE is the abnormality of immunoregulatory T cells, especially T4+ cells; 2. In active SLE, some of the T cells have been activated in vivo and these immunocompetent cells play an important role in immunoglobulin production of B cells; 3. The hyperactivity of humoral immunity is mainly related to the increase of PCA-1+ cells under the regulation of T cells; 4. Both the lymphocyte phenotypes and clinical features of SLE showed heterogeneity.