Clinical and cytological characteristics of serous effusions in 69 cases of lymphoma patients.

BACKGROUND: To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. METHODS: Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM) and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. RESULTS: The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. CONCLUSIONS: The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

Depletion of Igfbp7 alleviates zebrafish NAFLD progression through inhibiting hepatic ferroptosis.

AIMS: The global increased expression of Insulin-like growth factor binding protein 7 (IGFBP7) has been detected in non-alcoholic fatty liver disease (NAFLD) patients, however, its roles in NAFLD and the mechanism remain largely unclear. The goal of this study is to investigate the effect and mechanism of Igfbp7 using a zebrafish NAFLD model. MAIN METHODS: The igfbp7-/- null zebrafish mutant and the Igfbp7 liver overexpressed (LOE) transgenic zebrafish based on Gal4/UAS system were generated by CRISPR/Cas9 and Tol2 transgenic technique, respectively. The zebrafish NAFLD models in wildtypes, igfbp7-/- mutants and Igfbp7 LOE fishes have been established by high-fat diet feeding. The Igfbp7 dynamic expression and its effects on NAFLD progression have been detected and analyzed in both human NAFLD patients and zebrafish models. And the potential mechanism has been investigated through transcriptome analysis and subsequent detection and verification. KEY FINDINGS: High Igfbp7 levels in NASH and fibrosis stages have been detected in liver tissues of both human NAFLD patients and zebrafish models. Depletion of Igfbp7 significantly alleviated liver steatosis, inflammation, and fibrosis, whereas liver specific Igfbp7 overexpression dramatically exacerbated liver fibrosis in zebrafish NAFLD model. The hepatic iron deposition, lipid peroxidation products, and ferroptosis-related index were also significantly reduced at the NASH stage in the absence of Igfbp7. Igfbp7 promotes NAFLD progression through regulating ferroptosis, and Ncoa4-mediated ferritinophagy may be the pathway of Igfbp7-regulated ferroptosis. SIGNIFICANCE: Igfbp7 is confirmed as an important regulator in NAFLD progression. Depleting Igfbp7 effectively alleviates zebrafish NAFLD progression by inhibiting hepatic ferroptosis, suggesting a novel potential target for NAFLD treatment.

Screening of immune-related lncRNAs in lung adenocarcinoma and establishing a survival prognostic risk prediction model.

OBJECTIVE: This study aimed to improve lung adenocarcinoma (LUAD) prognosis prediction based on a signature of immune-related long non-coding RNAs (lncRNAs). METHODS: LUAD samples from the TCGA database were divided into the immunity_H group and the immunity_L group. Differentially expressed RNAs (DERs) between the two groups were identified. Optimized immune-related lncRNAs combination was obtained using LASSO Cox regression. A prognostic risk prediction (RS) model was built and further validated in the training and validation datasets. A network among lncRNAs in the RS model, their co-expressed DERs, and the related KEGG pathways were established. Critical lncRNAs were validated in LUAD tissue samples. RESULTS: In total, 255 DERs were obtained, and 11 immune-related lncRNAs were significantly related to prognosis. Six lncRNAs were demonstrated as an optimal combination for building the RS model, including LINC00944, LINC00930, LINC00607, LINC00582, LINC00543, and LINC00319. The KM curve and ROC curve revealed the RS model to be a reliable indicator for LUAD prognosis. LINC00944 and LINC00582 showed a co-expression relationship with the MS4A1. LINC00944, LINC00582, and MS4A1 were successfully validated in LUAD samples. CONCLUSION: We have established a promising LUAD patient survival prediction model based on six immune-related lncRNAs. For LUAD patients, this prognostic model could guide personalized treatment.

Clinicopathological features and genomic analysis of bronchiolar adenoma.

BACKGROUND: Bronchiolar adenoma (BA) is a rare tumor of the bronchioles with a double-layer structure, including the basal cell layer and the superficial cell layer, and it has a good prognosis. However, the concept of a putative variant of BA has been proposed in the recent literature. METHODS: Data on 17 cases of BA were collected from our center. The clinical data, morphology, immunophenotype, and molecular changes were retrospectively analyzed. We also collected the molecular changes in BA reported in the previous literature and summarized the putative driver mutations of BA. RESULTS: Out of 17 BAs, 13 were classic cases with a double-layer structure, including 9 proximal-type and 4 distal-type BAs. Of note, we also identified 3 cases that lacked a continuous basal cell layer, including 2 cases of mixed-type BA with monolayered lesions (basal cells were undetected in some areas) and 1 case of a monolayered BA-like lesion (basal cells were completely undetected). The immunohistochemical findings of monolayer cell lesions were closer to those of minimally invasive adenocarcinoma. We also found one case in which BA transformed into invasive adenocarcinoma accompanied by mutations in the TP53, JAK2, NF1 and RB1 genes. Combined with the previous literature, the most common putative driver gene mutations in 62 BA lesions were EGFR (25/62; 41%) and BRAF (21/62; 34.4%). CONCLUSION: Typical BA has a double-layer cell structure; however, there is also a putative variant of BA, which has a monolayer cell structure and lacks the basal cell layer. Transformation from BA into invasive adenocarcinoma is unusual but can occur.

Conversion of ER and HER2 Status After Neoadjuvant Therapy in Chinese Breast Cancer Patients.

BACKGROUND: Few studies have focused on converting ER-low-positive and HER2-low status following neoadjuvant therapy (NAT). We aimed to assess the evolution in ER and HER2 status after NAT in breast cancer patients. PATIENTS AND METHODS: Our study included 481 patients with residual invasive breast cancer after NAT. ER and HER2 status were assessed in the primary tumor and residual disease, and associations between ER and HER2 conversion and clinicopathological factors were explored. RESULTS: In primary tumors, 305 (63.4%) cases were ER-positive (including 36 cases of ER-low-positive), 176 (36.6%) were ER-negative. In residual disease, ER status changed in 76 (15.8%) cases, of which 69 cases switched from positive to negative. ER-low-positive tumors (31/36) were the most likely to change. In primary tumors, 140 (29.1%) tumors were HER2-positive, and 341 (70.9%) were HER2-negative (including 209 cases of HER2-low and 132 cases of HER2-zero). In residual disease, 25 (5.2%) cases had HER2 conversion between positive and negative. Considering HER2-low status, 113 (23.5%) cases had HER2 conversion, mostly driven by cases switching either to or from HER2-low. ER conversion had a positive correlation with pretreatment ER status (r = 0.25; P = .00). There was a positive correlation between HER2 conversion and HER2-targeted therapy (r = 0.18; P = .00). CONCLUSION: Conversion of ER and HER2 status was observed in some breast cancer patients after NAT. Both ER-low-positive and HER2-low tumors showed high instability from the primary tumor to residual disease. ER and HER2 status should be retested in residual disease for further treatment decisions, especially in ER-low-positive and HER2-low breast cancer.

A potential biomarker of esophageal squamous cell carcinoma WTAP promotes the proliferation and migration of ESCC.

This study focuses on the function of WTAP in esophageal squamous cell carcinoma (ESCC) samples and cell lines. The results showed that WTAP expression in ESCC tissues was significantly upregulated in 78.1% (57 of 73) of the ESCC tissues at the protein level compared with adjacent non-cancerous tissues via immunohistochemical staining. The WTAP protein expression level was positively correlated with the lymph node metastasis and TNM stage, and patients with higher WTAP protein expression level exhibited a shorter overall survival interval. Knocking down WTAP significantly reduced cell proliferation and migration but promoted cell apoptosis of TE-1and KYSE150 cells. Moreover, WTAP inhibition reduced the expression of ki67 and Snail related to cell proliferation and migration but increased the expression of Bax and Caspase-3 which were involved in cell apoptosis. In conclusion, our results suggest that the WTAP, a potential biomarker of ESCC, maybe play an important role in ESCC-genesis through regulating expression of genes related to cell proliferation, migration and apoptosis.

S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes.

The pathogenesis of type 2 diabetes mellitus (T2DM) is very complicated. The currently well-accepted etiology is the "Ominous Octet" theory proposed by Professor Defronzo. Since presently used drugs for T2DM have limitations and harmful side effects, studies regarding alternative treatments are being conducted. Analyzing the pharmacological mechanism of biomolecules in view of pathogenesis is an effective way to assess new drugs. Sphingosine 1 phosphate (S1P), an endogenous lipid substance in the human body, has attracted increasing attention in the T2DM research field. This article reviews recent study updates of S1P, summarizing its effects on T2DM with respect to pathogenesis, promoting ß cell proliferation and inhibiting apoptosis, reducing insulin resistance, protecting the liver and pancreas from lipotoxic damage, improving intestinal incretin effects, lowering basal glucagon levels, etc. With increasing research, S1P may help treat and prevent T2DM in the future.

Trends in the Use of Sphingosine 1 Phosphate in Age-Related Diseases: A Scientometric Research Study (1992-2020).

OBJECTIVES: This study was designed to explore the intellectual landscape of research into the application of sphingosine 1 phosphate (S1P) in age-related diseases and to identify thematic development trends and research frontiers in this area. METHODS: Scientometric research was conducted by analyzing bibliographic records retrieved from the Web of Science (WOS) Sci-Expanded Database dated between 1900 and 2020. Countries, institutions, authors, keyword occurrence analysis, and cooperation network analysis were performed using the CiteSpace and VOSviewer software. RESULTS: A total of 348 valid records were included in the final dataset, and the number of publications and the frequency of citations have grown rapidly over the last ten years. The USA (n = 175), China (n = 42), and Germany (n = 37) were the three largest contributors to the global publications on S1P and aging, while the Medical University of South Carolina (n = 15), University of California, San Francisco (n = 13), and University of Toronto (n = 13) were the leading institutions in this field. Analysis showed that early studies primarily focused on the mechanism of S1P intervention in AD. While S1P and its relevant metabolites have remained a long-term active area of research, recent studies have focused more on interventions aimed at improving retinal degeneration, cardiomyopathy, multiple sclerosis, and diabetes, among others. CONCLUSIONS: It is worth mentioning that this manuscript is the first to describe any bibliometric analysis of S1P and its application in age-related interventions. This study includes a discussion of the (1) historical overview of the topic; (2) main contributors: journals, countries, institutes, funding agencies, and authors; (3) collaboration between institutes and authors; (4) research hot spots and zones; and 5) research trends and frontiers. This will enable scholars to understand the current status of S1P research in age-related diseases.

Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells.

Apelin participates in cardiovascular functions, metabolic disease, and homeostasis disorder. However, the biological function of apelin in liver diseases, especially liver fibrosis is still under investigation. The present study aimed to investigate the expression of apelin in nonalcoholic fatty liver disease (NAFLD) and the mechanism of apelin promoting hepatic fibrosis through ERK signaling in hepatic stellate LX-2 cells. The results showed that the ALT and AST levels in serum were increased in the mice fed HFC. The histological staining revealed that hepatocellular steatosis and ballooning degeneration was severe, and fibrogenesis appeared as increased pericellular collagen deposition along with pericentral (lobular) collagen deposition in the mice fed HFC. Immunochemistry and qRT-PCR results showed that the expression of apelin and profibrotic genes was higher as compared to the control group. The in vitro experiments demonstrated that apelin-13 upregulated the transcription and translation levels of collagen type I (collagen-I) and α-smooth muscle actin (α-SMA) in LX-2 cells. The immunofluorescent staining, qRT-PCR, and Western blot results showed that the overexpression of apelin markedly increased the expression of α-SMA and cyclinD1. The LX-2 cells treated with apelin-13 displayed an increased expression of pERK1/2 in a time-dependent manner, while the pretreatment with PD98059 abolished the apelin-induced expression of α-SMA and cyclinD1. Furthermore, the in vivo and in vitro assays suggested a key role of apelin in promoting liver fibrosis, and the underlying mechanism might be ascribed to the apelin expression of profibrotic genes via ERK signaling pathway.