[Application strategy of artificial intelligence technology in feed-based development of medicinal and edible homologous traditional Chinese medicine(TCM)resources in era of the "antibiotic ban"].

In the context of the "antibiotic ban" era, the feed conversion of medicinal and edible traditional Chinese medicine(TCM) resources is a research hotspot in the field of antibiotic alternatives development. How to develop feed products that are beneficial to agriculture and livestock while ensuring nutrient balance and precision using medicinal and edible TCM resources as raw materials has become a challenge. Artificial intelligence(AI) technology has unique advantages in feed production and improving the efficiency of intelligent breeding. If AI technology is applied to the feed development of medicinal and edible TCM resources, it is possible to realize feeding and antibiotic-replacement value while ensuring precise nutrition. In order to better apply AI technology in the field of feed development of medicinal and edible TCM resources, this article used CiteSpace software to carry out literature visualization analysis and found that AI technology had a good application in the field of feed formulation optimization in recent years. However, there is still a gap in the research on the intelligent utilization of medicinal and edible TCM resources. Nonetheless, it is feasible for AI technology to be applied to the feed conversion of medicinal and edible TCM resources. Therefore, this article proposed for the first time an intelligent formulation system framework for feed materials derived from medicinal and edible TCM resources to provide new ideas for research in the field of feed development of medicinal and edible TCM resources and the research on the development of antibiotic alternatives. At the same time, it can pave the way for a new green industry chain for contemporary animal husbandry and the TCM industry.

Daphnia magna uptake and excretion of luminescence-labelled polystyrene nanoparticle as visualized by high sensitivity real-time optical imaging.

The environmental and ecological consequences of nanoplastics (NPs) draw increasing research interests and social concerns. However, the in situ and real-time detection of NPs from living organisms and transferring media remains as a major technical obstacle for scientific investigation. Herein we report a novel time-gated imaging (TGI) strategy capable of real-time visualizing the intake of NPs by an individual living organism, which is based on the polystyrene NPs labelled with lanthanide up-conversion luminescence. The limit of detection (LOD) of the TGI apparatus was 600 pg (SNR = 3) in a field of view of 2.4 × 3.8 mm. Taking Daphnia magna as the aquatic model, we investigated the dynamics of uptake and accumulation of NPs (500 µg/L) for 24 h, and the subsequent excretion process (in clean medium) for 48 h, and quantitively analyzed the distribution and the overall mass of NPs deposited in D. magna. The uptake of NPs via filter-feeding occurred in a few minutes, whereas a longer accumulation was found, in a timescale of several hours. And similar behaviors (bi-phase elimination) were also seen in the excretion, indicating the migration of NPs into the circulatory system. The average mass of NPs accumulated in an individual D. magna was ∼12 ng after 24 h exposure, indicating that D. magna as a filter feeder tends to retain NPs. The observed NPs accumulation in D. magna exemplifies the potential risk of aquatic ecosystem on exposure to NP contamination.

ROS/p53/miR­335­5p/Sp1 axis modulates the migration and epithelial to mesenchymal transition of JEG­3 cells.

Differential expression of microRNA (miR)­335­5p, a key tumor suppressor, has been detected in pre­eclampsia (PE) placentas. However, the role of miR­335­5p in the pathogenesis of PE and the factor modulating its aberrant expression remain unknown. The present study used JEG­3 cells in vitro to investigate these mechanisms. The role of miR­335­5p in proliferation, apoptosis and migration of JEG­3 cells was investigated using MTT, Annexin V­FITC/PI, Transwell migration and wound healing assays, respectively. miR­335­5p expression levels were analyzed using reverse transcription­quantitative PCR. The expression levels of E­cadherin, N­cadherin, Snail, specificity protein 1 (Sp1) and p53 were assessed using western blot analysis. Cell viability analysis was performed using the Cell Counting Kit­8 assay. The intracellular reactive oxygen species (ROS) levels were detected using a 2,7­dichlorodihydrofluorescein diacetate assay. The present results suggested that miR­335­5p did not affect the proliferation or apoptotic rate of JEG­3 cells. Overexpression of miR­335­5p significantly inhibited the migration of JEG­3 cells, decreased the expression levels of Sp1, N­cadherin and Snail, and increased E­cadherin expression. Sp1 silencing produced similar results in JEG­3 cells. H2O2 significantly increased the intracellular ROS levels and miR­335­5p expression, whereas N­acetyl­cysteine pretreatment prior to H2O2 treatment reversed the increases in miR­335­5p expression. Knockdown of p53 significantly decreased the expression levels of miR­335­5p in JEG­3 cells and in H2O2­treated cells. The present results suggested that miR­335­5p expression levels in trophoblast cells could be increased by ROS in a p53­dependent manner, leading to the downregulation of Sp1 and subsequent inhibition of epithelial to mesenchymal transition and cell migration. The present results may provide novel evidence on the etiology of PE.

Surgical management of Zollinger-Ellison syndrome: Classical considerations and current controversies.

Zollinger-Ellison syndrome (ZES) is characterized by gastric acid hypersecretion causing severe recurrent acid-related peptic disease. Excessive secretion of gastrin can now be effectively controlled with powerful proton pump inhibitors, but surgical management to control gastrinoma itself remains controversial. Based on a thorough literature review, we design a surgical algorithm for ZES and list some significant consensus findings and recommendations: (1) For sporadic ZES, surgery should be routinely undertaken as early as possible not only for patients with a precisely localized diagnosis but also for those with negative imaging findings. The surgical approach for sporadic ZES depends on the lesion location (including the duodenum, pancreas, lymph nodes, hepatobiliary tract, stomach, and some extremely rare sites such as the ovaries, heart, omentum, and jejunum). Intraoperative liver exploration and lymphadenectomy should be routinely performed; (2) For multiple endocrine neoplasia type 1-related ZES (MEN1/ZES), surgery should not be performed routinely except for lesions > 2 cm. An attempt to perform radical resection (pancreaticoduodenectomy followed by lymphadenectomy) can be made. The ameliorating effect of parathyroid surgery should be considered, and parathyroidectomy should be performed first before any abdominal surgery for ZES; and (3) For hepatic metastatic disease, hepatic resection should be routinely performed. Currently, liver transplantation is still considered an investigational therapeutic approach for ZES. Well-designed prospective studies are desperately needed to further verify and modify the current considerations.

WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma.

Although Wilms tumor 1 (WT1)-associated protein (WTAP) was initially found to be a specific WT1-binding protein, it has increasingly attracted attention because of its oncogenic role in various types of malignancies, including cholangiocarcinoma, glioblastoma and acute myeloid leukemia. However, the clinical impact of WTAP on pancreatic ductal adenocarcinoma (PDAC) is still unknown. A total of 145 patients who underwent surgical treatment from 2004 to 2008 were enrolled in the present study. The cytoplasmic and nuclear expression of WTAP in tumor and adjacent normal tissues was examined by immunohistochemical analysis in order to investigate the relationship between WTAP and the clinicopathological factors and prognosis of patients with PDAC. The nuclear and cytoplasmic expression of WTAP in tumor tissues was significantly higher compared with non-tumor tissues (P<0.001). High expression of WTAP in the nucleus was significantly associated with gender (P=0.010) and tumor stage (P=0.020), while high expression of WTAP in the cytoplasm was significantly associated with gender (P=0.018), histological grade (P=0.047) and perineural invasion (P=0.028). In addition, a univariate analysis revealed that high nuclear expression of WTAP in tumor tissues was significantly associated with poor overall survival (P<0.001), as well as several clinicopathological variables, including gender and N stage. In a multivariate Cox regression analysis, nuclear WTAP expression was identified as an independent prognostic indicator for PDAC (relative risk, 1.855; 95% confidence interval, 1.033-3.333; P=0.039). The results of the present study indicated that high nuclear expression of WTAP is a valuable molecular biomarker of a poor prognosis among patients with PDAC.

The Clinical Characteristics of Metanephric Adenoma: A Case Report and Literature Review.

We describe the clinical presentation, diagnosis, treatment, and follow-up data of a 39-year-old woman with asymptomatic right kidney tumor, which was later histopathologically diagnosed as metanephric adenoma (MA). Macroscopically, the tumor had integrity tegument with homogeneous and gray cutting surface. Microscopically, the tumor cells were formed in adenoid or papillary pattern and contained psammoma bodies, without distinctive atypia. Immunohistochemistry results showed they were negative for creatine kinase 7, epithelial membrane antigen, and renal cell carcinoma, and positive for AE1/AE3, vimentin, and Wilms Tumor 1. Pathological diagnosis was MA. The 48 months' follow-up information was available without recurrence.According to this case and literature review, we figured that it is difficult to make a definite diagnosis of MA only by image examination. Nephron-sparing surgery is eligible to treat MA. Long-term active surveillance is necessary because of the uncertainty of the biological behavior and cellular origin of MA.

Filamin A: Insights into its Exact Role in Cancers.

Filamin A (FlnA) is a well-known actin cross-linking protein. It serves as a scaffold for over 90 binding partners and involves in multiple cell functions, of which cell migration and adhesion is especially critical. Recently, its role in the cell has come under scrutiny for FlnA's involvement in cancer development. Originally revealed as a cancer-promoting protein, FlnA actually plays a dual role in cancers. When localized to the cytoplasm, FlnA has a tumor-promoting effect by interacting with signaling molecules. While once localized to the nucleus, it may act to suppress tumor growth and inhibit metastasis by interacting with transcription factors. Thus drugs that can cause FlnA to transpose from cytoplasm to nucleus could be a promising treatment for cancers. Study to this end is on the way in prostate cancer and the results are encouraging. FlnA has been studied in large categories of cancers, such as prostate cancer, breast cancer, melanoma, lung cancer, etc. However, most studies did not evaluate the differences that arise from the localization of the protein, which was a great pity! What's more, although FlnA's is undoubtedly important in cancer invasion and metastasis, both preclinical and clinical researches are very rare in some highly metastatic cancers, such as pancreatic cancer. In this mini-review, we give a comprehensive summary of FlnA' s expression in cancers. Where available, we also indicate the correlation of FlnA with cancer stages and patient prognosis, and clarify its localization (nucleus/cytoplasm) and its dual role (promote/suppress) in different cancers.

Expression and Significances of MTSS1 in Pancreatic Cancer.

Thus far, expression of metastasis suppressor 1 (MTSS1), its clinicopathologic and prognostic significances in pancreatic cancer (PC) remain unknown. Expression of MTSS1 was detected by Western blotting in PC cell lines, and by tissue microarray-based immunohistochemical staining in paired tumor and non-tumor samples from 242 patients with PC. Furthermore, the correlations between MTSS1 expression and clinicopathologic variables as well as overall survival were evaluated. In PC cell lines, MTSS1 was differentially expressed. In addition, MTSS1 expression was significantly lower in tumor than in non-tumor tissues (P < 0.001 in both McNemar and Mann-Whitney U tests). High tumoral expression of MTSS1 was closely associated with absence of lymph node metastasis (P = 0.023). Univariate analysis found that high MTSS1 expression in tumor tissues was a strong predictor of favorable overall survival in the whole cohort (P < 0.001). Besides, its impacts on prognosis were also observed in nine out of fourteen subgroups. Finally, MTSS1 expression was identified as an independent prognostic marker in the whole cohort (P = 0.031) as well as in six subgroups (P < 0.05), as shown by multivariate Cox regression test. Down-regulation of MTSS1 expression is evident in PC, and is associated with lymph node metastasis and poor prognosis.

Tigecycline-induced Drug Fever and Leukemoid Reaction: A Case Report.

In this study, we describe a patient in whom tigecycline-induced drug fever and leukemoid reaction (LR) after 3 weeks of therapy for pneumonia.A 62-year-old man developed aspiration pneumonia on February 1, 2015. He had received multiple antibiotics at another hospital, but did not respond well. Disease rapidly progressed, and he was referred to our department on February 14. We adjusted the antibiotic therapy to tigecycline + vancomycin, and added voriconazole to empiric antifungal therapy. Pneumonia largely improved, and we discontinued vancomycin and voriconazole on February 28. With tigecycline monotherapy, his clinical status remained stable.On March 7, he developed high fever and LR (white blood cell count: 38.25 × 10(9)/L). Erythrocyte sedimentation rate and C-reactive protein were elevated, and CD8+ T cells had been abnormally activated. After a careful physical examination and laboratory investigation, we confirmed that primary infection did not progress and no other cause was evident. So we figured fever and LR might be induced by tigecycline. After discontinuing tigecycline and adding low-dose steroid, fever and LR totally resolved in 3 days, which further confirmed our diagnosis.According to this case and literature review, drug-induced hypersensitivity should be considered in the differential diagnosis of fever and LR when the therapeutic duration of tetracycline approximates 3 weeks. Monitoring T-cell subsets may facilitate early diagnosis. When necessary, we should discontinue the suspected drug to confirm diagnosis.

Nuclear translocation of fibroblast growth factor receptor 3 and its significance in pancreatic cancer.

Nuclear translocation of fibroblast growth factor receptor 3 (FGFR3) was previously observed in some kinds of cancer. However, whether the phenomenon occurs in pancreatic cancer (PC), a malignancy with very dismal prognosis, remains unknown. In the present study, FGFR3 expression was firstly detected by Western blot and immunohistochemical staining in specimens of PC. Then, its correlations with clinicopathologic features and patient survival were evaluated. It was shown that FGFR3 was highly expressed in all the nuclear extracts, but in only one out of four whole tissue lysates, of tumor tissues, in contrast to those of non-tumor ones. Using immunohistochemistry, nuclear expression of FGFR3 was found to mainly locate in tumor cells, and was significantly associated with N stage. Furthermore, high FGFR3 nuclear expression was revealed to be associated with poor overall and disease-free survival in univariate analysis. For overall survival in the whole cohort and disease-free survival in patients with curative resection, high nuclear expression of FGFR3 was significant or marginally significant in multivariate analysis. However, its cytoplasmic expression was not related to clinical, pathologic variables and prognosis. These data suggest that nuclear translocation of FGFR3 is frequent and carries clinicopathologic as well as prognostic significances in PC.

Synergy between the ectoenzymes CD39 and CD73 contributes to adenosinergic immunosuppression in human malignant gliomas.

BACKGROUND: The importance of ectoenzymes CD39 and CD73 in mediating adenosinergic immunosuppression has been recognized, but their roles in human malignant glioma-associated immunosuppression remain largely unknown. METHODS: In this study, the ectoenzyme characteristics of malignant glioma cells and infiltrating CD4(+) T lymphocytes isolated from newly diagnosed malignant glioma patients were investigated. The ectoenzyme activities of both cell populations were determined by nucleotide hydrolysis assay. The immunosuppressive property of the CD39-CD73 synergic effect was evaluated via responder T-cell proliferation assay. RESULTS: We observed that CD39(-)CD73(+) glioma cells and infiltrating CD4(+)CD39(high)CD73(low) T lymphocytes exhibited 2 distinct but complementary ectoenzyme phenotypes, which were further verified by enzyme activity assay. The nucleotide hydrolysis cascade was incomplete unless CD39 derived from T lymphocytes and CD73 collaborated synergistically. We demonstrated that increased suppression of responder CD4(+) T-cell proliferation suppression was induced by CD4(+)CD39(+) T cells in the presence of CD73(+) glioma cells, which could be alleviated by the CD39 inhibitor ARL67156, the CD73 inhibitor APCP, or the adenosine receptor A2aR antagonist SCH58261. In addition, survival analysis suggested that CD73 downregulation was a positive prognostic factor related to the extended disease-free survival of glioblastoma patients. CONCLUSIONS: Our data indicate that glioma-derived CD73 contributes to local adenosine-mediated immunosuppression in synergy with CD39 from infiltrating CD4(+)CD39(+) T lymphocytes, which could become a potential therapeutic target for treatment of malignant glioma and other immunosuppressive diseases.

Tumor-infiltrating regulatory T cells are positively correlated with angiogenic status in renal cell carcinoma.

BACKGROUND: Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC. METHODS: Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations. RESULTS: Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05). CONCLUSIONS: These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.

OPN promotes survival of activated T cells by up-regulating CD44 in patients with oral lichen planus.

Oral lichen planus (OLP) is a chronic inflammatory disorder of oral mucosa, which represents cell-mediated autoimmune diseases. Pathological study demonstrated that abundant T lymphocytes infiltrated the oral mucosa, in which the activated T cells that trigger apoptosis of oral epithelial cells is an important mechanism for OLP. However, to date the molecular mechanisms underlying the T lymphocytes infiltration and accumulation in OLP remain unclear. In this paper, we found that the levels of plasma OPN were elevated and were associated with the up-regulated expressions of CD44 in OLP patients. In vitro, the addition of exogenous OPN can suppress the apoptosis of activated CD8(+) T cells via CD44, and this T cell resistance to apoptosis may be attributed to the reduction of endogenous mature granzyme B. Our results suggested that the abnormally elevated levels of OPN may contribute to the abnormal infiltration and accumulation of the activated T cells by up-regulating CD44 in OLP.

Expression of BAFF in the trophoblast and decidua of normal early pregnant women and patients with recurrent spontaneous miscarriage.

BACKGROUND: BAFF, the B cell activation factor, is a member of the tumor necrosis factor (TNF) ligand family that binds to BCMA, TACI, and BAFF-R. Previous studies have shown that members of the TNF family are detected in human placental trophoblast cells, but the expression patterns of BAFF involved in human decidua and the differential expression of BAFF between normal pregnancy and miscarriage are still incompletely documented or unknown. This study was designed to investigate the expression of BAFF and BAFF-R in the trophoblast and decidua of normal early pregnant women and recurrent spontaneous abortion (RSA) patients. METHODS: Forty-five patients with RSA and 45 normal pregnant women were included in this study. By reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical experiments, we explored the expression of BAFF and BAFF-R in the maternal-fetal interface of normal early pregnant women and RSA patients. RESULTS: Analysis by RT-PCR and Western blotting revealed that BAFF was detected in both trophoblast and decidua of all the samples, and the expression level was higher in the tissues of normal early pregnant women (P<0.05) than that of recurrent spontaneous abortion patients under the same gestational weeks. Messages for BAFF-R were absent. Immunohistochemical experiments showed that expression of BAFF was cell-specific which was localized to villous cytotrophoblast and syncytiotrophoblast cells in trophoblast and to stromal cells in decidua. Whereas BAFF was prominent on the trophoblast and decidua of normal early pregnant women, it was decreased in the tissues of RSA patients. CONCLUSIONS: BAFF might steer maternal leukocytes away from a harmful immune response and toward a favorable one and play a potentially vital role for successful pregnancy.

Membrane type 1-matrix metalloproteinase is involved in the migration of human monocyte-derived dendritic cells.

Dendritic cells (DC) are highly mobile APC. The trafficking of both immature and mature DC is crucial for their functions, which depends mainly on chemotactic attraction and matrix metalloproteinases (MMP) activity. MMP that are in a transmembrane form belong to membrane type (MT)-MMP, among which MT1-MMP has been shown to possess strong proteolytic activity that is capable of degrading extracellular matrix molecules. Although it is well established that MMP are zinc-dependent endopeptidases that collectively degrade most components of the extracellular matrix, relatively little is known about MT-MMP-mediated matrix degradation during DC migration. In this study, we showed that MT1-MMP was expressed in human monocyte-derived immature and mature DC by semi-quantitative reverse transcription PCR and western blotting analyses. Moreover, immunofluorescence microscopic studies showed that MT1-MMP was expressed on the membrane surface of DC. Blocking of MT1-MMP activity greatly reduced the invasion capacity of immature DC in Matrigel, whereas mature DC mobility was not affected. Taken together, our results show a novel functional link between MT1-MMP and DC motility and suggest that MT1-MMP may play an important role in modulating the migration of immature DC.