The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

Novel molecular classification and prognosis of papillary renal cell carcinoma based on a large-scale CRISPR-Cas9 screening and machine learning.

Papillary renal cell carcinoma (PRCC) is a highly heterogeneous cancer, and PRCC patients with advanced/metastatic subgroup showed obviously shorter survival compared to other kinds of renal cell carcinomas. However, the molecular mechanism and prognostic predictors of PRCC remain unclear and are worth deep studying. The aim of this study is to identify novel molecular classification and construct a reliable prognostic model for PRCC. The expression data were retrieved from TCGA, GEO, GTEx and TARGET databases. CRISPR data was obtained from Depmap database. The key genes were selected by the intersection of CRISPR-Cas9 screening genes, differentially expressed genes, and genes with prognostic capacity in PRCC. The molecular classification was identified based on the key genes. Drug sensitivity, tumor microenvironment, somatic mutation, and survival were compared among the novel classification. A prognostic model utilizing multiple machine learning algorithms based on the key genes was developed and tested by independent external validation set. Our study identified three clusters (C1, C2 and C3) in PRCC based on 41 key genes. C2 had obviously higher expression of the key genes and lower survival than C1 and C3. Significant differences in drug sensitivity, tumor microenvironment, and mutation landscape have been observed among the three clusters. By utilizing 21 combinations of 9 machine learning algorithms, 9 out of 41 genes were chosen to construct a robust prognostic signature, which exhibited good prognostic ability. SERPINH1 was identified as a critical gene for its strong prognostic ability in PRCC by univariate and multiple Cox regression analyses. Quantitative real-time PCR and Western blot demonstrated that SERPINH1 mRNA and protein were highly expressed in PRCC cells compared with normal human renal cells. This study exhibited a new molecular classification and prognostic signature for PRCC, which may provide a potential biomarker and therapy target for PRCC patients.

METTL14-m6A-FOXO3a axis regulates autophagy and inflammation in ankylosing spondylitis.

The role of m6A in ankylosing spondylitis (AS) remains largely obscure. In this study, we found that m6A modification was decreased in T cells of AS, and the abnormal m6A modification was attributed to the downregulation of methyltransferase-like 14 (METTL14). METTL14 exerted a critical role in regulating autophagy activity and inflammation via targeting Forkhead box O3a (FOXO3a). Mechanistically, the loss of METTL14 decreased the expression of FOXO3a, leading to the damage of autophagic flux and the aggravation of inflammation. Inversely, the forced expression of METTL14 upregulated the expression of FOXO3a, thereby activating autophagy and alleviating inflammation. Furthermore, our results revealed that METTL14 targeted FOXO3a mRNA and regulated its expression and stability in a m6A-dependent manner. These findings uncovered the functional importance of m6A methylation mechanisms in the regulation of autophagy and inflammation, which expanded our understanding of this interaction and was critical for the development of therapeutic strategies for AS.

Application of integrated problem-based learning combined with lecture-based classroom teaching in undergraduate medical education: An effective teaching model in a Medical School in China.

The problem-based learning (PBL) is increasingly used in undergraduate education. However, the application of integrated PBL to medical undergraduate education has not been well assessed. An observational study was designed to compare integrated PBL combined with lecture-based classroom (LBC) with traditional LBC teaching in 2 semesters of a Medical School in China. This study was conducted from March 2021 to July 2022. A total of 118 undergraduates majoring in clinical medicine were randomly allocated in 2 groups, 1 group receiving the integrated PBL + LBC teaching (experimental group, n = 60) and another group receiving LBC teaching (control group, n = 58). The experimental group attended the integrated PBL courses for the basic and clinical medicine conducted in the 6th and 8th semesters, respectively, as well as taking the LBC courses. The experimental group was required to preview the course materials before class, make presentations in class and take online feedback questionnaires after class, while the control group was required to preview the textbooks and listen to the traditional LBC courses. The students' scores of these 2 groups were compared, and feedback questionnaires were performed to evaluate the effectiveness of the experimental group over the control group. Results showed that the experimental group scored significantly higher than the control group in Clinical Skills (95% confidence interval [CI] 4.19-5.89), Internal Medicine I (95% CI: 1.85-9.93), Internal Medicine II (95% CI: 8.07-15.90), Introduction to Surgery (95% CI: 5.08-10.25), Surgery (General Surgery) (95% CI: 7.82-12.72), Surgery (Specialty) (95% CI: 6.47-9.97), and Clinical Medical Level Test (95% CI: 1.60-5.15) (all P < .01). In the feedback questionnaires of integrated PBL, up to 80% and 90% of students were satisfied with the teaching methods and lecturers, respectively. More than 80% of students agreed that the integrated PBL improved their abilities to learn independently, understand knowledge, and to raise, analyze and solve problems. In terms of stress in and out of class, a small number of students, <36.7%, felt stressed. The integrated PBL combined with LBC is an effective teaching approach, which may provide new ideas for teaching research and reform on undergraduate medical education in clinical medicine specialty and other medical majors.

Inhibition of MEG3 ameliorates cardiomyocyte apoptosis and autophagy by regulating the expression of miRNA-129-5p in a mouse model of heart failure.

The long non-coding RNA, maternally expressed gene 3 (MEG3), are involved in myocardial fibrosis and compensatory hypertrophy, but its role on cardiomyocyte apoptosis and autophagy in heart failure (HF) remains unclear. The aim of this study was to investigate the effect of MEG3 on cardiomyocyte apoptosis and autophagy and the underlying mechanism. A mouse model of HF was established by subcutaneous injection of isoproterenol (ISO) for 14 days, and an in vitro oxidative stress injury model was replicated with H2O2 for 6 h. SiRNA-MEG3 was administered in mice and in vitro cardiomyocytes to knock down MEG3 expression. Our results showed that cardiac silencing of MEG3 can significantly ameliorate ISO-induced cardiac dysfunction, hypertrophy, oxidative stress, apoptosis, excessive autophagy and fibrosis induced by ISO. In addition, inhibition of MEG3 attenuated H2O2-induced cardiomyocyte oxidative stress, apoptosis and autophagy in vitro. Downregulation of MEG3 significantly inhibited excessive cardiomyocyte apoptosis and autophagy induced by ISO and H2O2 through miRNA-129-5p/ATG14/Akt signaling pathways, and reduced H2O2-induced cardiomyocyte apoptosis by inhibiting autophagy. In conclusion, inhibition of MEG3 ameliorates the maladaptive cardiac remodeling induced by ISO, probably by targeting the miRNA-129-5p/ATG14/Akt signaling pathway and may provide a tool for pharmaceutical intervention.

Unique metabolism and protein expression signature in human decidual NK cells.

Human decidual natural killer (dNK) cells are a unique type of tissue-resident NK cells at the maternal-fetal interface. dNK cells are likely to have pivotal roles during pregnancy, including in maternal-fetal immune tolerance, trophoblast invasion, and fetal development. However, detailed insights into these cells are still lacking. In this study, we performed metabolomic and proteomic analyses on human NK cells derived from decidua and peripheral blood. We found that 77 metabolites were significantly changed in dNK cells. Notably, compared to peripheral blood NK (pNK) cells, 29 metabolites involved in glycerophospholipid and glutathione metabolism were significantly decreased in dNK cells. Moreover, we found that 394 proteins were differentially expressed in dNK cells. Pathway analyses and network enrichment analyses identified 110 differentially expressed proteins involved in focal adhesion, cytoskeleton remodeling, oxidoreductase activity, and fatty acid metabolism in dNK cells. The integrated proteomic and metabolomic analyses revealed significant downregulation in glutathione metabolism in dNK cells compared to pNK cells. Our data indicate that human dNK cells have unique metabolism and protein-expression features, likely regulating their function in pregnancy and immunity.

PAE ameliorates doxorubicin-induced cardiotoxicity via suppressing NHE1 phosphorylation and stimulating PI3K/AKT phosphorylation.

Doxorubicin (DOX), a broad-spectrum anti-tumor drug, has severe cardiotoxic side effects that limit its clinical application. Perillaldehyde (PAE) is the main component of volatile oil extracted from the stems and leaves of Herbaceous plant-perilla, which demonstrates antioxidant, anti-inflammatory, hypolipidemic, and other health functions. The present study aimed to explore the protective effect of perillaldehyde on DOX-induced cardiotoxicity in rats and to confirm its possible mechanism. The results showed that PAE could significantly improve cardiac function, alleviate myocardial fibrosis, and attenuate oxidative stress and inflammatory responses in DOX-induced cardiotoxicity in rats. Mechanistically, PAE could DOX-induced cardiotoxicity, which is related to its regulation of the PI3K/Akt signaling pathway and inhibition of NHE1 phosphorylation. Therefore, the finding demonstrates that perillaldehyde may be a promising cardioprotective agent for the prevention and treatment of cardiotoxicity caused by DOX.

Impaired autophagy and mitochondrial dynamics are involved in Sorafenib-induced cardiomyocyte apoptosis.

Sorafenib (Sor), a novel multi-target anticancer drug also induces severe toxicity in heart, while the mechanism of its cardiotoxicity remains to be fully elucidated. Dysregulation of autophagy and mitochondrial dynamics imbalance have been implicated in cardiomyocyte death. The aim of this study is to test the hypothesis that Sor disrupts autophagy and mitochondrial dynamics, thereby aggravating Sor-induced oxidative stress damage to cardiomyocytes. Our results revealed that Sor (≥ 5 µM) concentration- and time-dependently reduced cell viability and induced apoptosis in H9c2 myoblasts. Sor treatment promoted intracellular reactive oxygen species (ROS) generation, and subsequent Ca2+ overload as well as apoptosis, which were abolished by the ROS scavenger MPG. Sor inhibited the basal autophagy activity of cells, as supported by the fact that ERK1/2 inhibition-dependent decreases of autophagosomes and autolysosomes, and p62 accumulation in a concentration- and time-dependent manner. Improving autophagy with rapamycin abrogated Sor-induced ROS and Ca2+ overloads, and cell apoptosis. Furthermore, Sor compromised mitochondrial morphology and caused excessive mitochondrial fragmentation in cells. The imbalance of mitochondrial dynamics was attributed to ROS-mediated CaMKII overactivity, and increased phosphorylation of dynamin-related protein 1 (phosph-Drp1). Suppression of CaMKII with KN-93 or mitochondrial fission with mitochondrial division inhibitor-1 (Mdivi-1) attenuated Sor-induced ROS and Ca2+ overloads as well as apoptosis. In conclusion, these results provide the first evidence that impairments in autophagy and mitochondrial dynamics are involved in Sor-induced cardiomyocyte apoptosis. The present study may provide a potential strategy for preventing or reducing cardiotoxicity of Sor.

Tumor Endothelial Marker 8 Promotes Proliferation and Metastasis via the Wnt/ß-Catenin Signaling Pathway in Lung Adenocarcinoma.

Tumor endothelial marker 8 (TEM8), also known as ANTXR1, was highly expressed in cancers, and was identified as a biomarker for early diagnosis and prognosis in some cancers. However, the clinical role and molecular mechanisms of TEM8 in lung adenocarcinoma (LUAD) are still unclear. The present study aimed to explore its clinical value and the molecular mechanisms of TEM8 underlying the progression of LUAD. Our study found the elevation of TEM8 in LUAD cell lines and tissues. What's more, we observed that the TEM8 expression level was associated with tumor size, primary tumor, and AJCC stage, and LUAD patients with high TEM8 expression usually have a poor prognosis. Then, we conducted a series of experiments by the strategy of loss-of-function and gain-of-function, and our results suggested that the knockdown of TEM8 suppressed proliferation, migration, and invasion and induced apoptosis in LUAD whereas overexpression of TEM8 had the opposite effect. Molecular mechanistic investigation showed that TEM8 exerted its promoting effects mainly through activating the Wnt/ß-catenin signaling pathway. In short, our findings suggested that TEM8 played a crucial role in the progression of LUAD by activating the Wnt/ß-catenin signaling pathway and could serve as a potential therapeutic target for LUAD.

TFEB promotes BCL-2 expression by upregulating its promoter activity in the t(6;11) translocation renal cell carcinomas.

t(6;11) translocation renal cell carcinoma (RCC) is classified as a subset of the MiT family translocation RCCs and characterized by harboring the Alpha-TFEB fusion gene. However, the development mechanism of this tumor and its effective treatment have not been fully identified yet. The purpose of this study was to explore the relationship between TFEB and BCL-2 in Alpha-TFEB stably transfected cell lines and in t(6;11) RCC tumor tissue. An Alpha-TFEB eukaryotic expression vector was constructed and stably transfected into CaKi-2 and HK-2 cells. RT-PCR and real-time RT-PCR were used to measure the mRNA expressions of TFEB and BCL-2, and immunohistochemistry, Western blot and dual immunofluorescence assays were used to evaluate the TFEB and BCL-2 protein expressions. MTT proliferation assays and flow cytometry were also performed. Furthermore, luciferase reporter assays were used to evaluate the BCL-2 promoter activity. An Alpha-TFEB eukaryotic expression vector was successfully constructed and stably transfected into CaKi-2 and HK-2 cells (named CaKi-2-TFEB and HK-2-TFEB cells). Compared with the CaKi-2 and HK-2 groups, the TFEB and BCL-2 mRNA expression levels were significantly upregulated in the CaKi-2-TFEB and HK-2-TFEB groups respectively. The TFEB and BCL-2 protein expressions showed a similar result. The overexpression of TFEB and BCL-2 promoted cell proliferation and inhibited cell apoptosis. Moreover, the overexpression of TFEB upregulated the promoter activity of BCL-2. Our data suggest that the overexpression of TFEB promotes BCL-2 expression by upregulating its promoter activity and ultimately results in the development of t(6;11) translocation RCC. BCL-2 inhibitors may serve as potential therapeutic targets for t(6;11) translocation RCC.

N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8.

Although patients with early localized prostate cancer can survive longer, castration-resistant prostate cancer (CRPC) has gradually emerged with the use of androgen deprivation therapy (ADT). N-Myc and TEM8 play a vital role in the progression of several cancer types. However, the underlying mechanism of how N-Myc and TEM8 promote the progression of prostate cancer remains unclear. In this study, the expression of N-Myc and TEM8 was detected in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues by immunohistochemistry (IHC). LNCaP cell lines were maintained in RPMI 1640 medium supplemented with 10% charcoal-stripped fetal bovine serum. Subsequently, R language software was used to verify our results. Tubule formation assay of human umbilical vein endothelial cell (HUVEC) was conducted to examine the effect of N-Myc and TEM8 overexpression on angiogenesis in prostate cancer cells. IHC results showed a positive correlation between the expression of N-Myc and TEM8 in prostate cancer tissues. Further analysis showed that N-Myc and TEM8 were associated with clinicopathological features and poor prognosis in prostate cancer patients. Moreover, the overexpression of N-Myc and TEM8 promoted proliferation of prostate cancer cells and angiogenesis. Additionally, N-Myc and TEM8 overexpression was associated with therapeutic resistance. We further found that N-Myc promoted angiogenesis and therapeutic resistance in prostate cancer via TEM8. Hence, targeting N-Myc/TEM8 pathway in prostate cancer would be a novel therapeutic strategy to enhance the treatment of prostate cancer patients.

A proton-coupled folate transporter mutation causing hereditary folate malabsorption locks the protein in an inward-open conformation.

The proton-coupled folate transporter (PCFT, SLC46A1) is required for folate intestinal absorption and transport across the choroid plexus. Recent work has identified a F392V mutation causing hereditary folate malabsorption. However, the residue properties responsible for this loss of function remains unknown. Using site-directed mutagenesis, we observed complete loss of function with charged (Lys, Asp, and Glu) and polar (Thr, Ser, and Gln) Phe-392 substitutions and minimal function with some neutral substitutions; however, F392M retained full function. Using the substituted-cysteine accessibility method (with N-biotinyl aminoethyl methanethiosulfonate labeling), Phe-392 mutations causing loss of function, although preserving membrane expression and trafficking, also resulted in loss of accessibility of the substituted cysteine in P314C-PCFT located within the aqueous translocation pathway. F392V function and accessibility of the P314C cysteine were restored by insertion of a G305L (suppressor) mutation. A S196L mutation localized in proximity to Gly-305 by homology modeling was inactive. However, when inserted into the inactive F392V scaffold, function was restored (mutually compensatory mutations), as was accessibility of the P314C cysteine residue. Reduced function, documented with F392H PCFT, was due to a 15-fold decrease in methotrexate influx Vmax, accompanied by a decreased influx Kt (4.5-fold) and Ki (3-fold). The data indicate that Phe-392 is required for rapid oscillation of the carrier among its conformational states and suggest that this is achieved by dampening affinity of the protein for its folate substrates. F392V and other inactivating Phe-392 PCFT mutations lock the protein in its inward-open conformation. Reach (length) and hydrophobicity of Phe-392 appear to be features required for full activity.

Activated FMS-like tyrosine kinase 3 ameliorates angiotensin II-induced cardiac remodelling.

AIM: FMS-like receptor tyrosine kinase 3 (Flt3) has been reported to be increased in cardiomyocytes responding to ischaemic stress. This study was to determine whether Flt3 activation could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action. METHODS: In vivo cardiac hypertrophy and remodelling experiments were conducted by infusing angiotensin II (Ang II) chronically in male C57BL/6 mice. Flt3-specific ligand (FL) was administered intraperitoneally every two days (5 µg/mouse). In vitro experiments on hypertrophy, apoptosis and autophagy mechanism were performed in neonatal rat cardiomyocytes (NRCMs) and H9c2 cells with adenovirus vector-mediated overexpression of Flt3. RESULTS: Our results demonstrated that following chronic Ang II infusion for 4 weeks, the mice exhibited heart hypertrophy, fibrosis, apoptosis and contractile dysfunction. Meanwhile, Ang II induced autophagic responses in mouse hearts, as evidenced by increased LC3 II and decreased P62 expression. These pathological alterations in Ang II-treated mice were significantly ameliorated by Flt3 activation with FL administration. In NRCMs and Flt3-overexpressed H9c2 cells, FL attenuated Ang II-induced pathological autophagy and inactivated AMPK/mTORC1/FoxO3a signalling, thereby efficiently mitigating cell hypertrophy and apoptosis. Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II. CONCLUSION: Flt3 activation ameliorates cardiac hypertrophy, fibrosis and contractile dysfunction in the mouse model of chronic pressure overload, most likely via suppressing AMPK/mTORC1/FoxO3a-mediated autophagy. These results provide new evidence supporting Flt3 as a novel therapeutic target in maladaptive cardiac remodelling.

Cardiotoxicity of sorafenib is mediated through elevation of ROS level and CaMKII activity and dysregulation of calcium homoeostasis.

Sorafenib, a multi-kinase inhibitor, is recommended as a new standard therapy for advanced hepatocellular carcinoma (HCC); however, it also exhibits severe cardiotoxicity and the toxicity mechanisms are not completely elucidated. Recent studies suggested that sorafenib-enhanced ROS may partially contribute to its anti-HCC effect, which implies that redox mechanism might also be involved in sorafenib's cardiotoxicity. In this study, we aimed to investigate if sorafenib is able to induce oxidative stress and how this may impair cellular functions in cardiomyocyte, ultimately accounting for its cardiotoxicity. Our results showed that in isolated rat hearts, sorafenib caused ventricular arrhythmias and left ventricular dysfunction, which were alleviated by the antioxidant N-(2-mercaptopropionyl)-glycine (MPG). In isolated ventricular myocytes, sorafenib increased diastolic intracellular Ca2+ levels, decreased Ca transients and the occurrence of Ca2+ waves. These changes were eliminated by MPG, CaMKII inhibitor KN-93 and the mitochondrial permeability transition pore (mPTP)inhibitor cyclosporin A (CsA). Moreover, the levels of oxidized and phosphorylated CaMKII were significantly increased. Sorafenib elevated ROS levels, which was reversed by CsA and MPG; additionally, sorafenib reduced the activity of mitochondrial complex III and augmented mitochondrial ROS production. In vivo rats treated with sorafenib exhibited a reduction of antioxidant defence and abnormal histological alterations including hypertrophy, increased fibrosis, disordered myofibrils and damaged mitochondria, which were protected by MPG. We conclude that sorafenib induces the disruption of Ca2+ homoeostasis and cardiac injury via enhanced ROS potentially through inhibiting mitochondrial complex III, the opening of mPTP and overactivating CaMKII. These results provide a potential strategy for preventing or reducing cardiotoxicity of sorafenib.

Alpha gene upregulates TFEB expression in renal cell carcinoma with t(6;11) translocation, which promotes cell canceration.

Renal cell carcinoma (RCC) with t(6;11) translocation has been characterized by the fusion of the Alpha gene with the TFEB gene. However, the underlying molecular mechanisms remain greatly uncharacterized and effective targeted therapy has yet to be identified. In this study, we examined the role of the Alpha gene in this tumor entity and the function of the fusion gene Alpha-TFEB product in vitro and in vivo. Our results revealed that the luciferase activity of Alpha1, Alpha2, Alpha3, Alpha4 and Alpha5 significantly increased compared with that of the pGL3-Basic group (P<0.01). The luciferase activity also increased significantly in the Alpha1, Alpha2 and Alpha5 groups compared with that of the normal TFEB gene group (P<0.01). In addition, the luciferase activity of Alpha5 was the strongest located in the 643-693 base sequence. The stable transfection of Alpha-TFEB into HK-2 and CaKi-2 cells promoted the expression of Alpha-TFEB mRNA and TFEB protein. Furthermore, the overexpression of TFEB increased cell proliferation and enhanced the cell invasive ability, and decreased cell apoptosis in the Alpha-TFEB stably transfected cells in vitro. In vivo experiments revealed that the overexpression of TFEB promoted tumorigenicity in nude mice, which was consistent with our in vitro results. On the whole, these data indicate that the overexpression of TFEB confers a potent oncogenic signal and may thus be a novel therapeutic target in RCC with t(6;11) translocation.

LMO4 Is a Disease-Provocative Transcription Coregulator Activated by IL-23 in Psoriatic Keratinocytes.

Psoriasis is an autoimmune disease characterized by abnormal differentiation and hyperproliferation of epidermal keratinocytes. LIM-domain only protein 4 (LMO4) is a transcription factor coregulator that promotes the assembly of multiprotein complexes to regulate mammary epithelium and keratinocyte differentiation and proliferation during embryogenesis. In this study, LMO4 has been found to be abundantly expressed in psoriatic epidermis. LMO4 expression is increased in human keratinocytes induced to differentiate by calcium ex vivo, and LMO4 overexpression induces spontaneous differentiation and growth acceleration of human keratinocytes in the absence of calcium. IL-23, a cytokine highly expressed in psoriatic skin lesions, induces differentiation and promotes proliferation of human keratinocytes. The IL-23-mediated effects are accompanied by an increase in LMO4 expression mediated by signal transducer and activator of transcription 3 through an IL-23/acutely transforming retrovirus AKT8 in rodent T-cell lymphoma/signal transducer and activator of transcription 3 pathway in keratinocytes. Knockdown of LMO4 effectively inhibits differentiation and growth of keratinocytes both ex vivo and in IL-23-injected ears of mice. LMO4 appears to mediate IL-23-related responses in psoriatic keratinocytes and is a potential therapeutic target in psoriasis.

Probiotics for prevention of radiation-induced diarrhea: A meta-analysis of randomized controlled trials.

BACKGROUND: Radiotherapy is commonly used for abdominal or pelvic cancer, and patients receiving radiotherapy have a high risk developing to an acute radiation-induced diarrhea. Several previous studies have discussed the effect of probiotics on prevention of radiation-induced diarrhea, but the results are still inconsistent. OBJECTIVE: We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of probiotic supplementation for prevention the radiation-induced diarrhea. METHODS: Relevant RCTs studies assessing the effect of probiotic supplementation on clinical outcomes compared with placebo were searched in PubMed, EMBASE, and the Cochrane Library databases (up to March 30 2016). Heterogeneity was assessed with I2 and H2, and publication bias was evaluated using sensitive analysis. RESULTS: Six trials, a total of 917 participants (490 participants received prophylactic probiotics and 427 participants received placebo), were included in this meta-analysis. Compared with placebo, probiotics were associated with a lower incidence of radiation-induced diarrhea (RR: 0.55; 95% CI: 0.34-0.88; P = 0.01; I2: 87%; 95% CI: 75%-94%; H2: 2.8; 95% CI: 2.0-4.0). However, there is no significant difference in the anti-diarrheal medication use (RR: 0.68; 95% CI: 0.40-1.14; P = 0.14) or bristol scale on stool form (RR: 0.64; 95% CI: 0.35-1.17; P = 0.14). CONCLUSION: Probiotics may be beneficial to prevent radiation-induced diarrhea in patients who suffered from abdominal or pelvic cancers during radiotherapy period.

Computed Tomography and Magnetic Resonance Imaging Characteristics of Peripheral Primitive Neuroectodermal Tumor: A Retrospective Analysis of 16 Cases.

PURPOSE: The aim of this study was to analyze the radiological features of peripheral primitive neuroectodermal tumor (pPNET). MATERIALS AND METHODS: The radiological and clinical findings for 16 patients with pPNETs were retrospectively reviewed. The 16 tumors were classified into 4 groups (meninges group, n = 4; spine group, n = 3; bone group, n = 5; soft-tissue group, n = 4), and clinical data, size, and common and unique CT/MRI characteristics were assessed. RESULTS: Peripheral primitive neuroectodermal tumors presented as large solid masses with aggressive extension into the neighboring tissue. Most tumors (11/16) presented with necrosis, and 5 of the 16 cases showed signs of hemorrhage. The "dural tail sign" was observed in the meninges and spine groups. The pPNETs of bone demonstrated bony destruction with spiculated periosteal reaction, and small nourishing vessels were found in tumors in the soft-tissue group. CONCLUSIONS: Peripheral primitive neuroectodermal tumor should be suggested as an important differential diagnosis when the tumor presents as a large, ill-defined solid mass with aggressive extension and significant enhancement.

A case of PSF-TFE3 gene fusion in Xp11.2 renal cell carcinoma with melanotic features.

Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) with PSF-TFE3 gene fusion is a rare neoplasm. Only 22 cases of Xp11.2 RCCs with PSF-TFE3 have been reported to date. We describe an additional case of Xp11.2 RCC with PSF-TFE3 showing melanotic features. Microscopically, the histologic features mimic clear cell renal cell carcinoma. However, the dark-brown pigments were identified and could be demonstrated as melanins. Immunohistochemically, the tumor cells were widely positive for CD10, human melanoma black 45, and TFE3 but negative for cytokeratins, vimentin, Melan-A, microphthalmia-associated transcription factor, smooth muscle actin, and S-100 protein. Genetically, we demonstrated PSF-TFE3 fusion between exon 9 of PSF and exon 5 of TFE3. The patient was free of disease with 50 months of follow-up. The prognosis of this type of tumor requires more cases because of limited number of cases and follow-up period. Xp11.2 RCC with PSF-TFE3 inevitably requires differentiation from other kidney neoplasms. Immunohistochemical and molecular genetic analyses are essential for accurate diagnosis.