Objective:To explore the clinical features, histopathological morphology, and differential diagnosis of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers.Methods:From 2020 to 2021, 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers diagnosed in Fujian Cancer Hospital (2 cases) and the Second Affiliated Hospital of Fujian Medical University (2 cases) were collected. Different ancillary procedures such as HE, special stains, immunohistochemistry, and in situ hybridization techniques were used to assess the histopathological features and immunophenotypes. The clinical data were collected and literature was reviewed.Results:All 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers were male. They were 32, 45, 67 and 39 years old, respectively. The main clinical manifestations were bloody phlegm, abdominal pain, fatigue and anorexia. The clinical stages at diagnosis were stage Ⅳ (3 cases) and stage Ⅱ (1 case). Cases 2 and 3 had two pathological examinations at different sites, with a total of six pathological examinations. The histomorphology showed singly scattered or nests of tumor cells in a background of abundant small lymphocytes. The tumor cells were enlarged and pleomorphic, some appeared polygonal with inconspicuous cell borders, and they were arranged in a syncytial pattern. There were megakaryocytes, multinucleated tumor cells, and a few spindle-shaped cells seen. Atypical mitosis was commonly noted. By immunohistochemistry, the tumor cells were positive for CKpan(5/6), CK8/18(4/4), CAM5.2(2/5), CK-H(0/4), CK-L(3/4), EMA(4/5), CK5/6(3/6), p63(1/6), p40(1/6), E-cadherin (4/6), SSTR2(6/6), PD-L1(5/5), LCA(0/6), vimentin(5/6), CD2 (6/6), CD23(6/6), CD35(5/6), CXCL-13(4/5) and D2-40(1/5). The Ki-67 proliferative index was 60%-95%. In situ hybridization for EBER were all positive (6/6). Special stain for reticulin showed positive staining surrounding nests of tumor cells.Conclusions:The expression of follicular dendritic cell markers in lymphoepithelioma-like carcinoma is very rare, which may be related to EBV infection. Occasionally, it can overlap with follicular dendritic cell sarcoma by morphology and immunophenotype, which can lead to misdiagnosis. Only by combining clinical information, morphological characteristics and immunophenotype can an appropriate diagnosis be made.

Objective·To Investigate the effects of salidroside(SAL)on the immune response of macrophages infected with BCG.Methods·RAW264.7 mouse macrophages were infected with BCG,and the experiments were divided into blank control(BCG),salidroside(SAL+BCG),isoniazid(INH+BCG),and salidroside+isoniazid(SAL+INH+BCG)groups.The effects of SAL and INH on the proliferation of RAW264.7 cells were detected by MTT colorimetric assay,and the experimental concentrations of SAL and INH were screened.After the establishment of the BCG-infected macrophage model,intracellular bacterial survival was detected by bacterial plate count and flow cytometry following salidroside pretreatment.The levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),and interleukin-10(IL-10)in the culture supernatants were measured by enzyme-linked immunosorbent assay,and apoptosis levels were assessed by flow cytometry.Results·SAL at a concentration of 800 μmol/L and INH at 10 μmol/L were selected for subsequent experiments.Compared with the BCG group,SAL pretreatment for 36 h had the best effect,and the growth of BCG in macrophages in the administered group was inhibited.The inhibitory effect of the combined application of SAL and INH was obvious and statistically significant.Compared with the BCG group,SAL alone led to decreased secretion of TNF-α,IFN-γ,IL-6,and IL-10,although the differences were not statistically significant.However,the combination of SAL and INH caused a significant decrease in the levels of TNF-α,IL-6 and IL-10 in the supernatants of the cells(all P<0.05).Compared with the BCG group,in the early stage of the infection,SAL and INH were able to significantly reduce the apoptotic levels of BCG-infected RAW264.7 cells(P=0.008,P=0.032),and the combined application of SAL and INH significantly enhanced the apoptosis levels of BCG-infected RAW264.7 cells in the late stage of infection(P=0.001).Conclusion·In BCG-infected macrophages,SAL can exhibit antimycobacterial effects on the host by enhancing macrophage immune function,suppressing intracellular bacterial survival,and concurrently mitigating the inflammatory response elicited by BCG infection.

Objective·To Investigate the effects of salidroside(SAL)on the immune response of macrophages infected with BCG.Methods·RAW264.7 mouse macrophages were infected with BCG,and the experiments were divided into blank control(BCG),salidroside(SAL+BCG),isoniazid(INH+BCG),and salidroside+isoniazid(SAL+INH+BCG)groups.The effects of SAL and INH on the proliferation of RAW264.7 cells were detected by MTT colorimetric assay,and the experimental concentrations of SAL and INH were screened.After the establishment of the BCG-infected macrophage model,intracellular bacterial survival was detected by bacterial plate count and flow cytometry following salidroside pretreatment.The levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),and interleukin-10(IL-10)in the culture supernatants were measured by enzyme-linked immunosorbent assay,and apoptosis levels were assessed by flow cytometry.Results·SAL at a concentration of 800 μmol/L and INH at 10 μmol/L were selected for subsequent experiments.Compared with the BCG group,SAL pretreatment for 36 h had the best effect,and the growth of BCG in macrophages in the administered group was inhibited.The inhibitory effect of the combined application of SAL and INH was obvious and statistically significant.Compared with the BCG group,SAL alone led to decreased secretion of TNF-α,IFN-γ,IL-6,and IL-10,although the differences were not statistically significant.However,the combination of SAL and INH caused a significant decrease in the levels of TNF-α,IL-6 and IL-10 in the supernatants of the cells(all P<0.05).Compared with the BCG group,in the early stage of the infection,SAL and INH were able to significantly reduce the apoptotic levels of BCG-infected RAW264.7 cells(P=0.008,P=0.032),and the combined application of SAL and INH significantly enhanced the apoptosis levels of BCG-infected RAW264.7 cells in the late stage of infection(P=0.001).Conclusion·In BCG-infected macrophages,SAL can exhibit antimycobacterial effects on the host by enhancing macrophage immune function,suppressing intracellular bacterial survival,and concurrently mitigating the inflammatory response elicited by BCG infection.

Objective:To explore the clinical features, histopathological morphology, and differential diagnosis of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers.Methods:From 2020 to 2021, 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers diagnosed in Fujian Cancer Hospital (2 cases) and the Second Affiliated Hospital of Fujian Medical University (2 cases) were collected. Different ancillary procedures such as HE, special stains, immunohistochemistry, and in situ hybridization techniques were used to assess the histopathological features and immunophenotypes. The clinical data were collected and literature was reviewed.Results:All 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers were male. They were 32, 45, 67 and 39 years old, respectively. The main clinical manifestations were bloody phlegm, abdominal pain, fatigue and anorexia. The clinical stages at diagnosis were stage Ⅳ (3 cases) and stage Ⅱ (1 case). Cases 2 and 3 had two pathological examinations at different sites, with a total of six pathological examinations. The histomorphology showed singly scattered or nests of tumor cells in a background of abundant small lymphocytes. The tumor cells were enlarged and pleomorphic, some appeared polygonal with inconspicuous cell borders, and they were arranged in a syncytial pattern. There were megakaryocytes, multinucleated tumor cells, and a few spindle-shaped cells seen. Atypical mitosis was commonly noted. By immunohistochemistry, the tumor cells were positive for CKpan(5/6), CK8/18(4/4), CAM5.2(2/5), CK-H(0/4), CK-L(3/4), EMA(4/5), CK5/6(3/6), p63(1/6), p40(1/6), E-cadherin (4/6), SSTR2(6/6), PD-L1(5/5), LCA(0/6), vimentin(5/6), CD2 (6/6), CD23(6/6), CD35(5/6), CXCL-13(4/5) and D2-40(1/5). The Ki-67 proliferative index was 60%-95%. In situ hybridization for EBER were all positive (6/6). Special stain for reticulin showed positive staining surrounding nests of tumor cells.Conclusions:The expression of follicular dendritic cell markers in lymphoepithelioma-like carcinoma is very rare, which may be related to EBV infection. Occasionally, it can overlap with follicular dendritic cell sarcoma by morphology and immunophenotype, which can lead to misdiagnosis. Only by combining clinical information, morphological characteristics and immunophenotype can an appropriate diagnosis be made.

Liver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound.

ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI/CLA-1) are the key proteins in reverse cholesterol transport (RCT). The high expression of ABCA1 and SR-BI/CLA-1 can decrease the danger of atherosclerosis. The purpose of the study is to find ABCA1 and CLA-1up-regulators for treating atherosclerosis by using cell-based high throughput screening models. Among 20 000 compounds screened, E0869 [1-(3, 4-dimethylphenyl)-1-oxopropan-2-yll4-((methylsulfonyl)methyl)benzoate] was found as the positive hit. The up-regulated activities of E0869 in ABCAl1-LUC and bCA-l1-LUC HepG2 cell were 160% and 175%, respectively. The EC50 values of E0869 in ABCAl1-LUC and CLA-l1-LUC HepG2 cell were 3.79 and 1.42 pμol- x ,(-1) respectively. E0869 could upregulate the mRNA and protein levels of ABCA1, SR-BI/CLA-1 and ABCGJ1genes in HepG2 and RAW264.7 cells by Real-Time Quantitative PCR and Western blotting analysis, but could not influence the expression of FAS, SREBP-l1 and CD36. Foam cell assay showed that E0869 could inhibit lipids accumulation in mouse peritoneal macrophages RAW264.7. Cholesterol efflux assay showed that E0869 could induce HDL-mediated cholesterol efflux in mouse peritoneal macrophages RAW264.7. In conclusion, E0869 could up-regulate ABCA1 and CLA-1 activity, and had good anti-atherosclerotic activity in vitro.

In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.