Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Emerging multidrug resistant (MDR) Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases. To combat these MDR Salmonella typhimurium pathogens, highly effective and broad-spectrum antibiotics such as flufenicol (FFC) need to be evaluated for their potent antibacterial activity against Salmonella typhimurium. However, the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR. In this work, we develop a novel nano-formulation, flufenicol nano-micelles (FTPPM), which are based on d-α-tocopherol polyethylene glycol 1,000 succinate (TPGS)/poloxamer 188 (P188), for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine. Herein, FTPPM were prepared via a thin film hydration method. The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems, which can further decrease production costs. The optimized FTPPM demonstrated outstanding stability and sustained release. An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy (68.17 %) than did florfenicol-loaded TPGS polymer micelles (FTPM), flufenicol active pharmaceutical ingredients (FFC-API), and flufenicol commercially available medicine (FFC-CAM), and also exhibited outstanding biocompatibility. Notably, FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms. More importantly, FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice. In summary, FTPPM significantly improved the solubility and oral bioavailability of florfenicol, enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo. FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.
Humans ; Rituximab/therapeutic use* ; Vincristine/therapeutic use* ; Prednisone/therapeutic use* ; Epstein-Barr Virus Infections/drug therapy* ; Herpesvirus 4, Human ; Neoplasm Recurrence, Local ; Lymphoma, T-Cell/drug therapy* ; Cyclophosphamide/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Doxorubicin/therapeutic use* ; Lymphadenopathy/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To study clinicopathologic features, prognosis and differential diagnoses of primary mucosal CD30-positive T-cell lymphoproliferative disorders of the head and neck(mCD30⁺ TLPD-head and neck). Methods: Three cases of mCD30⁺ TLPD-head and neck were collected from January 2014 to April 2017 at Sun Yat-Sen University Foshan Hospital. A literature review of mCD30⁺ TLPD of head and neck was provided. Results: All three cases presented with either bulging/exophytic nodule or mucosal ulcer/erosion. Morphologically, the tumor consisted of diffuse proliferation of uniform, large atypical mononuclear lymphoid cells that showed irregular or polymorphic nuclei with small nucleoli, and abundant pale or amphophilic cytoplasm. Hallmark cells with eccentric, horseshoe, kidney-like, or doughnut-shaped nuclei were present. While mitotic figures were present, no tumor necrosis was found. Eosinophilc infiltration was obvious in the background. The atypical large lymphoid cells had a immunophenotype of CD30⁺ /CD3⁺ /CD4⁺ /CD56^- along with positive cytotoxic molecule. While being negative for EBER/ALK/CD20/CD8, TCR rearrangement was found in 2 out of 3 cases. Three patients were cured after excision without relapse and metastasis.The two patients with TCR rearrangement didn′t show aggressive clinical course. Conclusions mCD30⁺ TLPD-head and neck is a rare benign lymphoproliferative disorder with spontaneous regression. It should be differentiated from cutaneous CD30⁺ anaplstic large cell lymphoma, lymphomatoid papulosis, and EBV-related mucocutaneous ulcer. Correct recognition of mCD30⁺ TLPD of head and neck is important to avoid overtreatment.

Objective: To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo.Methods: Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively.The change of mouse activity, tumor formation, tumor size and survival time were observed respectively.And the femur tissue and spinal tissue were obtained from the mice after death.The gray value of iconography were measured by imageological examination of femur tissue, and the final histopathological examination were taken to determine the tumor type in both femur and spinal tissue.Results: The tumor growth could be touched at the puncture site in all the mice after inoculated for 7 days.There were no obvious differences in the time of tumorigenesis, the rate of tumor growth and tumor size among the mice in the same group (P>0.05).As the result, the construction femoral bone and lumbar vertebra metastatic models of PCa had been confirmed by iconography and pathology detection.At the same time, the survival time of the mice inoculated with low concentrations of PCa cells was obviously longer than that of high concentrations of PCa cells (at least 2 weeks longer).Conclusion: The animal models with different positional osseous metastasis (limbs and axial skeleton) of PCa using the same PCa cells (RM-1) had been first constructed successfully in our study.At the same time, a high success rate of construction of PCa animal model with bone metastasis was obtained by femoral bone marrow cavity injection of PCa cells.The rate of tumor growth was rapid, animal survival time was appropriate, and the PCa animal model with bone metastasis can be stably reproduced by our method.These animal models can be used to explore the pathogenesis of different positional PCa bone metastasis and provide a new platform, which were more congruous to clinical process, for prevention and cure of neoplastic bone metastases.

Aged ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Lymphoma, Large B-Cell, Diffuse ; virology

Purpose To analyze and summarize morphological characteristics, the immune phenotype, diagnosis and differential diag-nosis, clinical features and prognosis of epithelioid angiomyolipomas retrospectively, to deepen understanding of EAML and improve the diagnostic accuracy. Methods The pathological morphology was observed and immunohistochemistry of phenotypic characteristics were analyzed in 7 cases of epithelioid angiomyolipomas. Results Seven cases of epithelioid angiomyolipomas had similar morphology:larger tumor cells, ovoid, fusiform or polygonal, with abundant and eosinophilic cytoplasm, a big nucleus of different size with obvious nucleoli, polynuclear and gaint tumor cells, with a few mitotic figures. The tumor cells arranged in nests or sheets, cuff-shaped around the blood vessels. Immunohistochemistry showed that the tumor cells were positive for HMB-45, Melan-A, vimentin and SMA, but negative for EMA, CK, and CD10. All of them underwent radical surgery or surgical resection, and were followed up for 3~56 months after operation. 6 cases were alive, without recurrence and metastasis, while 1 case died of gastrointestinal stromal sarcomas 3 months later. Conclusion Epithelioid angiomyolipomas belong to mesenchymal tumors with malignant potential, pathological morphology would be easily misdiagnosed as malignant tumors. Immunohistochemistry plays an important role in the differential diagnosis. Surgical treatment is the main method at present, with possibility of recurrence or metastasis.

ObjectiveTo explore the expression of novel protein kinase C ε (PKCε) in normal prostate (NP) tissue, benign prostate hyperplasia(BPH), peficancerous (PC) tissue and prostate cancer (Pca), and study its correlation with the grade and stage of Pca.MethodsTen NP slides, ten BPH slides, ten PC slides and 43 Pca slides were collected from our hospital. These slides were routinely proceased and analyzed according to the requirement of immunohistochemical staining. Tumors were classified according to the 2002 TNM staging system. The grading system used in the study was based on the Gleason grade.ResultsWe was found that the expression of PKCεs in Pca (27/43) were significantly higher than those in NP(1/10), BPH (0/10) and PC (2/10) tissue, and the difference was statistically significant ( P ＜0.05 ). With regard to grade of prostate cancer, the expression of PKCε in Pca with Gleason score ≥8 group (12/13) was higher than the Gleason score 2 -4 group (4/10) and the Gleason score 5 -7 group (11/20). The difference was statistically significant (P ＜ 0.05 ). Moreover, the T3 and T4 stages had a more positive rate (10/12 & 9/10) than the T1 and T2 stages( 1/6 &7/15). There is statistically significant difference between early and advanced stage of prostate cancer ( P ＜ 0. 05 ). Furthermore, the positive expression of PKCε in prostatic carcinoma samples increased significantly in the metastasis group (9/10)compared to the non-metastasis group ( 18/33 ) ( P ＜ 0. 05 ), but the difference was not statistically significant between the concentration of prostate-specific antigen in blood serum ( P ＞ 0. 05 ).Conclusions PKCε is expressed in prostate cancer, and it correlates with the grade and stage of prostate cancer. PKCε may be related to the origin and the development of Pca, and it may be used as a prognostic factor for Pca.

Objective To evaluate the prognostic value of intraoperalive detection in rib bone marrow micmmetastasis(BMMs)of patients with non-small-cell lung cancer(NSCLC)and the relationship between the micROmetast ases and clinicopathologic factors.Method From April 2004 to May 2007,146 patients undergoing surgical treatment for NSCLC were prospectively investigated for the presence of BMMs by the immunohistochemisury method.Remits 30.82%(45/146)of NSCLC patients were detected with BMMs,15(33.33%)patients developed remote metastases of the 45 patients with BMMs,14(13.86%)patients developed metastases of the 101 patients without BMMs.Patients with BMMs demonstrated an earlier metastasis and a lower survival rate compared with patients without BMMs(P＜0.05).There Was trend for ahigher frequency and the occurrence of BMMs changed with tumor stages and the histologic differentiation of the tumor.No relationship was found between BMMs and age,T grade,as well as tumor dimension.Conclusions The detection of BMMs can predict the prognosis of NSCLC patients and identifies patients withNSCLC who are at significantly increased risk for metastasis and survival,which may be useful in evalnatingpatients for adjuvant treatment