Duodenal Soft Tissue Sarcoma with GLI1 Gene Rearrangement: A Case Report and Literature Review.

BACKGROUND Soft tissue tumors have various subtypes, among which sarcomas exhibit high malignant potential and poor prognosis. Malignant epithelioid tumor with GLI1 alterations was originally found in myopericytoma with t(7;12) translocation. However, recent studies indicated that it is a distinct tumor type characterized by multiple nodular distributions of oval or round epithelioid cells with a rich capillary network and a lack of specific immunophenotype. There are only a few cases reported worldwide and the optimal treatment is still being explored. CASE REPORT We report the case of a 31-year-old patient who presented with severe anemia and a large soft tissue mass in the duodenum. The patient underwent surgical resection with a negative margin, and none of the 15 lymph nodes tested positive for the tumor. Postoperative pathology and FISH testing further confirmed the presence of GLI1 disruption and S-100 and SMA negativity. Genetic testing revealed the ACTB-GLI1 fusion. No specific medication was offered after the surgery. No tumor recurrence was found during the 23-month follow-up period. The patient's quality of life is currently satisfactory. CONCLUSIONS Soft tissue sarcomas characterized by GLI1 gene rearrangement have a relatively less aggressive and metastatic nature, with the solid mass spreading minimally even as it grows. Patients can benefit from surgical resection, resulting in a relatively long period of tumor-free survival.

Metabolic reprogramming directed by super-enhancers in tumors: An emerging landscape.

Metabolic reprogramming is an essential hallmark of tumors, and metabolic abnormalities are strongly associated with the malignant phenotype of tumor cells. This is closely related to transcriptional dysregulation. Super-enhancers are extremely active cis-regulatory regions in the genome, and can amalgamate a complex set of transcriptional regulatory components that are crucial for establishing tumor cell identity, promoting tumorigenesis, and enhancing aggressiveness. In addition, alterations in metabolic signaling pathways are often accompanied by changes in super-enhancers. Presently, there is a surge in interest in the potential pathogenesis of various tumors through the transcriptional regulation of super-enhancers and oncogenic mutations in super-enhancers. In this review, we summarize the functions of super-enhancers, oncogenic signaling pathways, and tumor metabolic reprogramming. In particular, we focus on the role of the super-enhancer in tumor metabolism and its impact on metabolic reprogramming. This review also discusses the prospects and directions in the field of super-enhancer and metabolic reprogramming.

The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance.

AIMS: Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. METHODS: A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis- and chemoresistance-related genes using gene expression data of PC, and the model was applied to single-cell RNA sequencing data. The influence of linker histone H1.2 (H1-2) on PC was explored through in vitro and in vivo experiments including proliferation, invasion, migration, drug sensitivity, rescue experiments and immunohistochemistry, emphasizing its regulation with c-MYC signaling pathway. RESULTS: A novel MCS scoring system accurately predicted PC patient survival and was linked to chemoresistance and epithelial-mesenchymal transition (EMT) in PC single-cell RNA sequencing data. H1-2 emerged as a significant prognostic factor, with its high expression indicating increased chemoresistance and EMT. This upregulation was mediated by c-MYC, which was also found to be highly expressed in PC tissues. CONCLUSION: The MCS scoring system offers insights into PC chemoresistance and metastasis potential. Targeting H1-2 could enhance therapeutic strategies and improve PC patient outcomes.

Saikosaponin a ameliorates diet-induced fatty liver via regulating intestinal microbiota and bile acid profile in laying hens.

Fatty liver hemorrhagic syndrome is a widespread metabolic disease in laying hens that decreases egg production and even causes death in severe cases. Many traditional Chinese medicine ingredients, such as saikosaponin a (SSa), have been shown to alleviate fatty liver, but the underlying mechanisms remain unclear. In this study, we aimed to explore the alleviation of dietary SSa on excessive hepatic lipid deposition and the interactions between intestinal microbiota and bile acid (BA) in laying hens. Fifty-four 35-wk-old laying hens were randomly allocated into 3 treatment groups with 6 replicates (3 birds per replicate) and fed with a basal diet (CON), high-energy and low-protein diet (HELP), and HELP diet with 30 mg/kg SSa (HELP + SSa). SSa reversed diet-induced egg production rate decrease (P < 0.05). SSa could potently ameliorate HELP-induced accumulation of hepatic cholesterol and liver injury via the increase (P < 0.05) of mRNA expression of BA synthesis gene, such as cholesterol 7 alpha-hydroxylase 1. SSa treatment alleviated gut dysbiosis, especially reducing (P < 0.05) the relative abundance of bile salt hydrolase (BSH)-producing bacteria such as Lactobacillus, Bifidobacterium, and Turicibacter. Ileal BA metabolomic analysis revealed that SSa increased (P < 0.05) the content of tauro-conjugated BAs, mainly taurochenodeoxycholic acid and tauro-α-muricholic acid. The mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 19 were decreased (P < 0.05) in intestine, which was associated with increased gene expression of enzymes in the BA synthesis that reduced the levels of cholesterol. Moreover, SSa treatment inhibited intestinal BA reabsorption via decreasing (P < 0.05) the mRNA expression of apical sodium-dependent bile acid transporter. Our findings indicated that SSa reduced liver cholesterol accumulation and alleviated fatty liver in laying hens through microbiota-BA-intestinal FXR crosstalk.

Emerging roles of ferroptosis-related miRNAs in tumor metastasis.

Ferroptosis, a novel mode of cell death dependent on iron and reactive oxygen species, has been extensively explored during malignant tumors metastasis. Ferroptosis can interact with multiple components of the tumor microenvironment to regulate metastasis. These interactions generally include the following aspects: (1) Epithelial-mesenchymal transformation, which can help cancer cells increase their sensitivity to ferroptosis while they have multiple mechanisms to fight against it; (2) Disorder of iron metabolism in cancer stem cells which maintains their stem characteristics; (3) Polarization of M0 macrophages to M2. (4) The paradoxical effects of iron metabolism and CD8 + T cells induced by ferroptosis (5) Regulation of angiogenesis. In addition, ferroptosis can be regulated by miRNAs through the reprogramming of various intracellular metabolism processes, including the regulation of the glutathione- glutathione peroxidase 4 pathway, glutamic acid/cystine transport, iron metabolism, lipid metabolism, and oxidative stress. Therefore, there are many potential interactions between ferroptosis-related miRNAs and tumor metastasis, including interaction with cancer cells and immune cells, regulating cytokines, and angiogenesis. This review focuses on the role of ferroptosis-related miRNA in tumor metastasis, aiming to help readers understand their relationship and provide a new perspective on the potential treatment strategies of malignant tumors.

Emerging role of ferroptosis-related circular RNA in tumor metastasis.

Tumor metastasis is an important factor that contributes to the poor prognosis of patients with tumors. Therefore, to solve this problem, research on the mechanism of metastasis is essential. Ferroptosis, a new mode of cell death, is characterized by membrane damage due to lipid peroxidation caused by iron overload. Many studies have shown that excessive ferroptosis can affect tumor metastasis and thus inhibit tumor progression. Recently, circular RNA (circRNA), a type of non-coding RNA, has been shown to be associated with the progression of ferroptosis, thus influencing tumor development. However, the specific mechanisms by which circRNAs affect the progression of ferroptosis and their roles in tumor metastasis are not known. In this review, we systematically discuss the role of circRNAs in regulating tumor ferroptosis and their mechanism of action through sponging miRNAS in various tumors, thereby impacting metastasis. This review helps elucidate the relationship and role of ferroptosis-related circRNAs in tumor metastasis and may provide future researchers with new ideas and directions for targeted therapies.

[Corrigendum] CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and ERK1/2 phosphorylation.

Subsequently to the publication of the above article, the authors contacted the Editorial Office to explain that they had inadvertently included data from the same original source in the first row of data panels in Fig. 4B on p. 2191 (showing the results of cell migration assay experiments) to represent two differently performed experiments. Specifically, these images (second and third data panels) containing partially overlapping data corresponded to the 'Vacant­BGC823' in the empty plasmid transfection group and the background 'BGC823 cell' groups, respectively. However, the authors had retained their original data, which they presented to the office for our inspection, and were able to reassemble the data correctly in the figure. The revised version of Fig. 4, showing the replacement data for the 'Vacant­BGC823' and 'BGC823' Migration panels in Fig. 4B, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 48: 2184­2196, 2016; DOI: 10.3892/ijo.2016.3428].

Quercetin alleviates intestinal inflammation and improves intestinal functions via modulating gut microbiota composition in LPS-challenged laying hens.

Quercetin, a well-known flavonoid, has been demonstrated to exert beneficial effects on intestinal functions and gut microbiota in birds. In this study, we investigated the effects of quercetin supplementation on inflammatory responses, intestinal barrier functions and gut microbial community in LPS-challenged laying hens. A total of two hundred eighty-eight 32-wk-old Jingfen No.6 laying hens were randomly assigned to 3 groups, the CON group, the LC group and the LQ group. LQ group was fed with 0.4 mg/kg quercetin and at the end of 12 wk, LC and LQ groups were challenged intraperitoneally with lipopolysaccharide (LPS). After LPS challenge, 8 birds of each group were randomly selected and sampled. LPS challenge induced an obvious intestinal mucosal injury, necrosis and shedding, while quercetin intervention maintained its structure. Quercetin significantly decreased the elevated malondialdehyde contents (P < 0.05), and increased the activity of total antioxidant capacity and glutathione peroxidase (P < 0.05) in intestinal mucosa of LPS-challenged laying hens. Quercetin rescued the LPS-induced decreases in goblet cell density and mucin2 expression levels (P < 0.05). There was a significant decline (P < 0.05) in the mRNA expression of Claudin1 and Occludin in intestinal mucosa of LPS-challenged layers, which could be alleviated (P < 0.05) by dietary quercetin. LPS challenge induced the increased expression levels (P < 0.05) of IL-1ß and TLR-4 in intestinal mucosa, while these rises could be reversed (P < 0.05) following dietary quercetin supplementation. LPS challenge induced a shift in gut microenvironment, and quercetin addition could elevate the relative abundance of some short chain fatty acids (SCFA)-producing or health-promoting bacteria such as Phascolarctobacterium, Negativicutes, Selenomonadales, Megamonas, Prevotellaceae, and Bacteroides_salanitronis. In conclusion, dietary quercetin addition ameliorated the LPS challenge-induced intestinal inflammation and improved intestinal functions, possibly associated with its modulation on gut microbiota, particularly the increased population of SCFA-producing bacteria.

Intermittent Pringle maneuver combined with controlled low Central venous pressure prolongs hepatic hilum occlusion time in patients with hepatocellular carcinoma complicated by post hepatitis B cirrhosis: a randomized controlled trial.

Background: The optimal occlusion and reperfusion time to balance blood loss and ischemia-reperfusion injury to the remnant liver remains unclear. The aim was to explore the clinical impact of prolonging the hepatic hilum occlusion time from 15 to 20 min using the intermittent Pringle maneuver (IPM) combined with controlled low central venous pressure (CLCVP).Methods: A total of 151 patients were included and divided into an experimental group (Group 20,75 cases) and a control group (Group 15,76 cases). In both groups, the hepatic hilum was blocked by the IPM combined with CLCVP to control intraoperative hepatic cross-sectional bleeding. The preoperative, intraoperative and postoperative parameters and safety were compared between the two groups.Results: There were no significant differences between the two groups in the postoperative aminotransferase serum levels (p > 0.05). However, the operation time in Group 20 was significantly lower than that in Group 15 (222.4 ± 87.8 vs. 250.7 ± 94.5 min, p < 0.05). The procalcitonin at 1 day after operation in Group 20 was lower than that at 1 day after operation in Group 15 (0.78 ± 0.66 vs. 1.45 ± 1.33 ng/mL, p < 0.05). There was no significant difference in the incidence of postoperative bleeding, postoperative bile leakage and postoperative infection between the two groups (p > 0.05).Conclusions: For patients with hepatocellular carcinoma after hepatitis B cirrhosis, it is feasible and safe to prolong the hepatic hilum occlusion time from 15 to 20 min using the IPM combined with CLCVP.

Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and Ca2+ release from the ER.

Uncoupling protein 2 (UCP2), a mitochondrial protein, is known to be upregulated in pancreatic islets of patients with type 2 diabetes (T2DM); however, the pathological significance of this increase in UCP2 expression is unclear. In this study, we highlight the molecular link between the increase in UCP2 expression in ß-cells and ß-cell failure by using genetically engineered mice and human islets. ß-cell-specific UCP2-overexpressing transgenic mice (ßUCP2Tg) exhibited glucose intolerance and a reduction in insulin secretion. Decreased mitochondrial function and increased aldolase B (AldB) expression through oxidative-stress-mediated pathway were observed in ßUCP2Tg islets. AldB, a glycolytic enzyme, was associated with reduced insulin secretion via mitochondrial dysfunction and impaired calcium release from the endoplasmic reticulum (ER). Taken together, our findings provide a new mechanism of ß-cell dysfunction by UCP2 and AldB. Targeting the UCP2/AldB axis is a promising approach for the recovery of ß-cell function.

Imeglimin Ameliorates ß-Cell Apoptosis by Modulating the Endoplasmic Reticulum Homeostasis Pathway.

The effects of imeglimin, a novel antidiabetes agent, on ß-cell function remain unclear. Here, we unveiled the impact of imeglimin on ß-cell survival. Treatment with imeglimin augmented mitochondrial function, enhanced insulin secretion, promoted ß-cell proliferation, and improved ß-cell survival in mouse islets. Imeglimin upregulated the expression of endoplasmic reticulum (ER)-related molecules, including Chop (Ddit3), Gadd34 (Ppp1r15a), Atf3, and Sdf2l1, and decreased eIF2α phosphorylation after treatment with thapsigargin and restored global protein synthesis in ß-cells under ER stress. Imeglimin failed to protect against ER stress-induced ß-cell apoptosis in CHOP-deficient islets or in the presence of GADD34 inhibitor. Treatment with imeglimin showed a significant decrease in the number of apoptotic ß-cells and increased ß-cell mass in Akita mice. Imeglimin also protected against ß-cell apoptosis in both human islets and human pluripotent stem cell-derived ß-like cells. Taken together, imeglimin modulates the ER homeostasis pathway, which results in the prevention of ß-cell apoptosis both in vitro and in vivo.

Fermented Corn-Soybean Meal Mixed Feed Modulates Intestinal Morphology, Barrier Functions and Cecal Microbiota in Laying Hens.

This study aimed to evaluate the effects of fermented corn-soybean meal mixed feed on intestinal barrier function and cecal microbiota in laying hens. A total of 360 Jingfen No.6 laying hens (22 wk-old) were assigned to 4 dietary treatments, which were offered basal diets (without antibiotics) containing 0, 4, 6 and 8% of fermented mixed feed respectively. The results showed that the pH value and anti-nutritional factor concentrations in fermented mixed feed were lower than those in unfermented feed (p < 0.05). Moreover, fermentation in the feed significantly increased the crude protein content (p < 0.05). Supplementation with fermented feed significantly reduced the crypt depth and increased the villi height:crypt depth ratio of duodenum and jejunum (p < 0.05). Meanwhile, fermented feed increased the secretory immunoglobulin A content and MUC2 mRNA expression of jejunum (p < 0.05). These beneficial effects were exhibited at the addition level ≥6% and microbial composition of caeca in the control, and so 6% fermented feed groups were analyzed. The structure of the gut microbiota was remarkably altered by additions, characterized by increased abundances of some health-promoting bacteria, such as Parasutterella, Butyricicoccus and Erysipelotrichaceae (p < 0.05). In summary, fermented mixed feed modulated cecal flora, subsequently contributing to improvements in intestinal morphology and barrier functions in laying hens.

Immediate Glucose-Lowering Effect After the First Administration of Dulaglutide: A Retrospective, Single-Center, Observational Study.

INTRODUCTION: Dulaglutide is a long-acting glucagon-like peptide 1 receptor agonist that is administered once weekly for the treatment of type 2 diabetes. However, the immediate glucose-lowering effect of dulaglutide after the first administration and the factors affecting the efficacy of the drug remain unclear. METHODS: This study was a retrospective and observational study of 80 subjects with type 2 diabetes conducted in a hospitalized setting. The changes (Δ) in the blood glucose (BG) levels at six time points (6-point BG levels) from the baseline (day - 1) to the day after the first administration of 0.75 mg of dulaglutide (day 1) were evaluated. The associations of the Δ 6-point BG levels with the patients' characteristics and laboratory data were also analyzed. RESULTS: Significant reduction of the fasting BG, preprandial BG, postprandial BG, and standard deviation (SD) of the 6-point BG levels was observed on day 1 as compared to day - 1 (P < 0.0001) and the reduced BG levels were maintained throughout the remaining observation period of 5 days. The baseline serum hemoglobin A1c and glycoalbumin levels were positively correlated with the reduction of the fasting BG. The Δ BG levels were not related to the parameters of insulin-secreting capacity. Insulin treatment was positively associated with the reduction of the 6-point BG levels. Patients without cerebrovascular disease and patients without diabetic retinopathy showed greater improvements of the fasting BG and SD of the 6-point BG levels, respectively. Urinary microalbumin level was positively correlated with improvements of the 6-point BG levels. Dulaglutide reduced the BG levels, irrespective of the previously used class of antidiabetic medication(s). CONCLUSION: Dulaglutide achieved reduction in glucose level within 24 h of the first injection. The improvement in the BG levels remained stable for a week in the hospitalized clinical setting.

The Feasibility and Applicability of Stem Cell Therapy for the Cure of Type 1 Diabetes.

Stem cell therapy using islet-like insulin-producing cells derived from human pluripotent stem cells has the potential to allow patients with type 1 diabetes to withdraw from insulin therapy. However, several issues exist regarding the use of stem cell therapy to treat type 1 diabetes. In this review, we will focus on the following topics: (1) autoimmune responses during the autologous transplantation of stem cell-derived islet cells, (2) a comparison of stem cell therapy with insulin injection therapy, (3) the impact of the islet microenvironment on stem cell-derived islet cells, and (4) the cost-effectiveness of stem cell-derived islet cell transplantation. Based on these various viewpoints, we will discuss what is required to perform stem cell therapy for patients with type 1 diabetes.

Sesamin protects against DSS-induced colitis in mice by inhibiting NF-κB and MAPK signaling pathways.

OBJECTIVE: To investigate the protective effects and mechanisms of sesamin (SES) on dextran sulfate sodium (DSS)-induced experimental colitis in mice. METHODS: SES (50, 100, and 200 mg kg-1) were orally administered to C57BL/6 male mice after DSS instillation. The anti-inflammatory effect of SES on colonic damage was assessed by clinical, macroscopic, microscopic, and inflammatory signaling pathways. RESULTS AND CONCLUSIONS: It could be found that bodyweight and colon length of mice treated with DSS was significantly decreased while that were increased by SES treatment. SES treatment reduced the DAI values and improved the histopathology of the colon in the DSS-treated mice. SES also reduced TNF-α, IL-1ß and IL-6 production caused by DSS. We also measured the expression of the phosphorylation of p65, IκB, p38, ERK and JNK protein and found that SES can alleviate colon damage via the NF-κB and MAPK signaling pathways. The findings of this study suggested that SES had anti-inflammatory effects on intestinal inflammation and can be used as a new therapeutic candidate for inflammatory bowel disease.

Soluble EGFR, a hepatokine, and adipsin, an adipokine, are biomarkers correlated with distinct aspects of insulin resistance in type 2 diabetes subjects.

BACKGROUND: Insulin resistance can occur in all metabolic organs including the liver, adipose tissue, and skeletal muscles. Circulating soluble epidermal growth factor receptor (soluble EGFR) and adipsin levels are altered in obese diabetic mice and are possibly correlated with insulin resistance in both mice and humans. Here, we investigated the significance of soluble EGFR and adipsin as biomarkers for insulin resistance in Japanese subjects with type 2 diabetes. METHODS: We measured the soluble EGFR and adipsin levels in sera from 47 non-diabetic subjects and 106 subjects with type 2 diabetes using enzyme-linked immunosorbent assays (ELISAs) and analyzed the correlations between the soluble EGFR or adipsin levels and metabolic parameters in type 2 diabetes subjects. We also measured the gene expression levels of Egfr and Cfd (adipsin) in the liver, adipose tissue, and skeletal muscle in mice with/without obesity or diabetes. RESULTS: The soluble EGFR levels were correlated with the fasting blood glucose level (P = 0.010), HOMA-IR (P = 0.035), HbA1c level (P = 0.007), HDL-cholesterol level (P = 0.044), and FIB-4 index (P = 0.017) after adjustments for age, sex, and total cholesterol levels. These factors are known to be related to hepatic insulin resistance. The serum adipsin levels were correlated with BMI (P < 0.001), waist circumference (P < 0.001), fasting serum insulin level (P = 0.001), HOMA-IR (P = 0.009), CPR-index (P = 0.045), and FIB-4 index (P = 0.007) after adjustments for age, sex and eGFR levels. Abdominal adiposity leads to the potentiation of these factors. The expression of Egfr was abundant in the liver, while Cfd was predominantly expressed in adipose tissue in mice. CONCLUSIONS: Soluble EGFR, a hepatokine, is correlated with insulin resistance in the liver, while adipsin, an adipokine, is associated with adipose insulin resistance.Trial registration: UMIN Clinical Trials Registry (www.umin.ac.jp), UMIN000020474. Registered 8 January 2016.

Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor.

Abnormal hepatic insulin signaling is a cause or consequence of hepatic steatosis. DPP-4 inhibitors might be protective against fatty liver. We previously reported that the systemic inhibition of insulin receptor (IR) and IGF-1 receptor (IGF1R) by the administration of OSI-906 (linsitinib), a dual IR/IGF1R inhibitor, induced glucose intolerance, hepatic steatosis, and lipoatrophy in mice. In the present study, we investigated the effects of a DPP-4 inhibitor, linagliptin, on hepatic steatosis in OSI-906-treated mice. Unlike high-fat diet-induced hepatic steatosis, OSI-906-induced hepatic steatosis is not characterized by elevations in inflammatory responses or oxidative stress levels. Linagliptin improved OSI-906-induced hepatic steatosis via an insulin-signaling-independent pathway, without altering glucose levels, free fatty acid levels, gluconeogenic gene expressions in the liver, or visceral fat atrophy. Hepatic quantitative proteomic and phosphoproteomic analyses revealed that perilipin-2 (PLIN2), major urinary protein 20 (MUP20), cytochrome P450 2b10 (CYP2B10), and nicotinamide N-methyltransferase (NNMT) are possibly involved in the process of the amelioration of hepatic steatosis by linagliptin. Thus, linagliptin improved hepatic steatosis induced by IR and IGF1R inhibition via a previously unknown mechanism that did not involve gluconeogenesis, lipogenesis, or inflammation, suggesting the non-canonical actions of DPP-4 inhibitors in the treatment of hepatic steatosis under insulin-resistant conditions.

EBV-positive intravascular large B-cell lymphoma of the liver: a case report and literature review.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare subtype of diffuse large B-cell lymphoma that most commonly involves the central nervous system, skin, and bone marrow. To our knowledge, Epstein-Barr virus (EBV)-positive IVLBCL in the liver has never been reported in the literature. CASE PRESENTATION: We report a case of a 65-year-old Chinese man with complaint of fever for 18 days. No obvious abnormality was found by physical examination. Laboratory findings were notable for anemia, thrombocytopenia, and elevated level of serum lactate dehydrogenase. Bone marrow on smear, biopsy, and flow cytometry revealed no lymphoma. Imaging studies showed a slightly lower density lesion in the liver with high fluorodeoxyglucose uptake and hepatosplenomegaly. Percutaneous liver biopsy revealed clustering of large atypical lymphocytes within the hepatic sinusoids. Immunohistochemically, these lymphoma cells were positive for CD20, PAX-5, MUM-1, BCL-6 and CD5, but negative for CD3 and CD10. Besides, Epstein-Barr virus-encoded RNA was detected in tumor cells by in situ hybridization. BCL-2, BCL-6 and MYC genes were intact tested by fluorescence in situ hybridization analysis. The patient was diagnosed as IVLBCL and died after 1 month of hospitalization without receiving immunochemotherapy. CONCLUSIONS: IVLBCL of the liver is a highly rare lymphoma with nonspecific manifestations and dismal prognosis. Full recognition of its clinicopathological features will help to better diagnose this disease.

Madecassoside Protects Against LPS-Induced Acute Lung Injury via Inhibiting TLR4/NF-κB Activation and Blood-Air Barrier Permeability.

Madecassoside (MA), a crucial ingredient of Centella asiatica, has been reported to exhibit a variety of bioactivities, including antipulmonary fibrosis, and antiinflammatory effects. Here we aimed to elucidate the protective effects and underlying mechanisms of MA on LPS-induced acute lung injury (ALI). The mice were treated with MA for one week and then received intratracheal of LPS to establish the ALI model. Then we evaluated the pathological changes by haematoxylin and eosin staining and measured the levels of proinflammatory cytokines and myeloperoxidase (MPO) by ELISA, the transcriptional level of tight junction proteins by qRT-PCR, as well as the expression of Toll-like receptor4/Nuclear factor kappa-B (TLR4/NF-κB) pathway by Western blot. The results showed that MA significantly inhibited LPS-induced pathological damages, lung edema, MPO, and proinflammatory cytokines production. Furthermore, MA obviously repaired alveolar epithelium integrity showing by reduced secretion of total proteins in the BALF and enhanced mRNA expression of tight junction as Occludin and zonula occludens-1 (ZO-1) comparing to LPS. Further research showed that LPS stimulation activated the TLR4/NF-κB signaling pathway and the activation was inhibited by MA. In conclusion, these data indicated that MA had protective effects against LPS-induced ALI. The therapeutic mechanisms may be associated with reducing the alveolar epithelium permeability and inflammatory response via repressing the activation of TLR4/NF-κB pathway.

In vitro high-throughput drug sensitivity screening with patient-derived primary cells as a guide for clinical practice in hepatocellular carcinoma-A retrospective evaluation.

AIM: The aim of the study was to determine the clinical value of in vitro high-throughput drug sensitivity screening with primary hepatocellular carcinoma cells to select drugs for adjuvant chemotherapy. METHODS: This study included 162 patients who underwent hepatectomy from September 2013 to December 2016. The patients were divided into a drug sensitivity screening group and an empirical treatment group. High-throughput drug sensitivity screening using primary HCC cells was carried out and, based on the test results, effective drugs were selected for treatment. Patients in the empirical group were treated with commonly used drugs, according to the clinicians' preferences. Clinical efficacy, i.e., disease-free survival (DFS) time, was compared between the two groups. RESULTS: Most patients with HCC showed extensive resistance to known chemotherapeutic drugs. However, bortezomib, regorafenib, sorafenib, romidepsin, hydroxycamptothecin and adriamycin+oxaliplatin showed strong anti-HCC activity in the sensitivity assay. Comparing clinical efficacy, the overall median DFS of patients in the drug sensitivity screening group was significantly better than that of patients in the empirical treatment group (17.00±3.80 months vs. 9.00±1.18 months, P=0.001). Median DFS times in the TACE group were 9.00±4.07 months vs. 7.00±1.06 months (P=0.014) and median DFS times in the oral drugs group were 16.80±3.98 months vs. 10.00±0.81 months (P=0.024). Patients DFS was 69.4%, 62.5% at 1-, 2- years, respectively, for patients with drug sensitivity screening, and 48.5%, 37.8% at 1-, 2- years, respectively, for patients with empirical treatment. CONCLUSION: High-throughput drug sensitivity screening can be successfully used to screen chemotherapeutic drugs for efficacy against HCC and the efficacious drugs can be used in postoperative adjuvant chemotherapy of HCC patients. This treatment paradigm is safe and reliable, and improves survival compared with empirical chemotherapy.