Evaluating pediatric ureteropelvic junction obstruction:Dynamic magnetic resonance urography vs renal scintigraphy 99mtechnetium mercaptoacetyltriglycine

BACKGROUND Ureteropelvic junction obstruction(UPJO)is a common congenital urinary tract disorder in children.It can be diagnosed as early as in utero due to the presence of hydronephrosis or later in life due to symptomatic occurrence.AIM To evaluate the discrepancy between dynamic contrast-enhanced magnetic resonance urography(dMRU)and scintigraphy 99m-technetium mercaptoacetyltriglycine(MAG-3)for the functional evaluation of UPJO.METHODS Between 2016 and 2020,126 patients with UPJO underwent surgery at Robert DebréHospital.Of these,83 received a prenatal diagnosis,and 43 were diagnosed during childhood.Four of the 126 patients underwent surgery based on the clinical situation and postnatal ultrasound findings without undergoing functional imaging evaluation.Split renal function was evaluated preoperatively using scintigraphy MAG-3(n=28),dMRU(n=53),or both(n=40).In this study,we included patients who underwent surgery for UPJO and scintigraphy MAG-3+dMRU but excluded those who underwent only scintigraphy MAG-3 or dMRU.The patients were divided into groups A(<10%discrepancy)and B(>10%discrepancy).We examined the discrepancy in split renal function between the two modalities and investigated the possible risk factors.RESULTS The split renal function between the two kidneys was compared in 40 patients(28 boys and 12 girls)using scintigraphy MAG-3 and dMRU.Differential renal function,as determined using both modalities,showed a difference of<10%in 31 children and>10%in 9 children.Calculation of the relative renal function using dMRU revealed an excellent correlation coefficient with renal scintigraphy MAG-3 for both kidneys.CONCLUSION Our findings demonstrated that dMRU is equivalent to scintigraphy MAG-3 for evaluating split renal function in patients with UPJO.

The mechanisms of melanogenesis inhibition by glabridin:molecular docking,PKA/MITF and MAPK/MITF pathways

Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.

海原断裂干盐池探槽揭示非特征性古地震序列

海原断裂是青藏高原东北缘一条重要的陆内活动左旋走滑断裂,于1920年发生过里氏8?级特大地震,形成约230km的地表破裂带和高达10.2m的同震左旋位移。该断裂的大地震复发行为特征一直是地震地质学家关注的重点,然而现有的认识需要更多以精细沉积地层约束的古地震数据的验证。基于此,在海原断裂中段干盐池盆地成功开挖了数个大型三维探槽,揭露了清晰的韵律性、面状展布地层和丰富的古地震事件证据。在探槽上部2.5m厚的最新细粒沉积层序记录了AD 1500以来的3次地震事件。基于地层中^(14)C样品的结果和历史地震史料的考证,限定这3次地震事件分别对应于AD 1920年、AD 1760年(或1709年)和AD 1638年的地震,但其震级差别很大。除了最新一次地震,即1920年海原大地震的震级为8?级,其他2次地震事件的震级较小,均小于7级,说明海原断裂上伴生有地表破裂的地震不全是特征型地震事件。结果表明,古地震探槽中揭示的地震强度不一定相同,而且中等震级地震也可以产生地表破裂,其地层证据在合适的条件下,如无沉积间断、沉积速率大等环境能在地层中得到保存。

Colorectal cancer and immunity:what we know and perspectives

Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer.In particular,the density of T CD8+and CD45+lymphocyte infiltration was recently shown to have a better prognostic value than the classic tumor node metastasis classification factor.Other immune subsets,as macrophages,natural killer cells or unconventionnal lymphocytes,seem to play an important role.Induction of regulatory T cells(Tregs)or immunosuppressive molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response.The development of these mechanisms is a major obstacle to the establishment of an effective immune response,but also to the use of immunotherapy.Although im-munotherapy is not yet routinely used in colorectal cancer,we now know that most treatments used(chemotherapy and biotherapy)have immunomodulatory effects,such as induction of immunogenic cell death by chemotherapy,inhibition of immunosuppression by antiangiogenic agents,and antibody-dependent cytotoxicity induced by cetuximab.Finally,many immunotherapy strategies are being developed and tested in phaseⅠtoⅢclinical trials.The most promising strategies are boosting the immune system with cytokines,inhibition of immunoregulatory checkpoints,vaccination with vectorized antigens,and adoptive cell therapy.Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effective immunotherapy for treatment of colorectal cancer in the near future.

Assessment of liver ablation using cone beam computed tomography

AIM: To investigate the feasibility and accuracy of cone beam computed tomography(CBCT) in assessing the ablation zone after liver tumor ablation.METHODS: Twenty-three patients(17 men and 6 women, range: 45-85 years old, mean age 65 years) with malignant liver tumors underwent ultrasoundguided percutaneous tumor ablation [radiofrequency(n = 14), microwave(n = 9)] followed by intravenous contrast-enhanced CBCT. Baseline multidetector computed tomography(MDCT) and peri-procedural CBCT images were compared. CBCT image quality was assessed as poor, good, or excellent. Image fusion was performed to assess tumor coverage, and quality of fusion was rated as bad, good, or excellent. Ablation zone volumes on peri-procedural CBCT and post-procedural MDCT were compared using the nonparametric paired Wilcoxon t-test.RESULTS: Rate of primary ablation effectiveness was 100%. There were no complications related to ablation. Local tumor recurrence and new liver tumors were found 3 mo after initial treatment in one patient(4%). The ablation zone was identified in 21/23(91.3%) patients on CBCT. The fusion of baseline MDCT and peri-procedural CBCT images was feasible in all patients and showed satisfactory tumor coverage(at least 5-mm margin). CBCT image quality was poor, good, and excellent in 2(9%), 8(35%), and 13(56%), patients respectively. Registration quality between periprocedural CBCT and post-procedural MDCT images was good to excellent in 17/23(74%) patients. The median ablation volume on peri-procedural CBCT and post-procedural MDCT was 30 cm3(range: 4-95 cm3) and 30 cm3(range: 4-124 cm3), respectively(P-value > 0.2). There was a good correlation(r = 0.79) between the volumes of the two techniques. CONCLUSION: Contrast-enhanced CBCT after tumor ablation of the liver allows early assessment of the ablation zone.

Hepatitis B and human immunodeficiency virus co-infection

Hepatitis B and human immunodeficiency virus(HBV and HIV)infection share transmission patterns and risk factors,which explains high prevalence of chronic HBV infection in HIV infected patients.The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection,faster progression to cirrhosis and higher risk of liver-related death in HIVHBV co-infected patients than in HBV mono-infected ones.HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma.Noninvasive tools are now available to evaluate liver fibrosis.Isolated hepatitis B core antibodies(anti-HBc)are a good predictive marker of occult HBV infection.Still the prevalence and significance of occult HBV infection is controversial,but its screening may be important in the management of antiretroviral therapy.Vaccination against HBV infection is recommended in non-immune HIV patients.The optimal treatment for almost all HIV-HBV co-infectedpatients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation.Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen.The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.

Gastric emptying evaluation by ultrasound prior colonoscopy:An easy tool following bowel preparation

AIM: To investigate the gastric emptying after bowel preparation to allow general anaesthesia. METHODS: A prospective, non-comparative, and nonrandomized trial was performed and registered on Eudra CT database(2011-002953-80) and on www.trial.gov(NCT01398098). All patients had a validated indication for colonoscopy and a preparation using sodium phosphate(NaP) tablets. The day of the procedure, patients took 4 tablets with 250 mL of water every 15 min, three times. The gastric volume wasestimated every 15 min from computed antral surfaces and weight according to the formula of Perlas et al(Anesthesiology, 2009). Colonoscopy was performed within the 6 h following the last intake.RESULTS: Thirty patients were prospectively included in the study from November 2011 to May 2012. The maximum volume of the antrum was 212 mL, achieved 15 min after the last intake. 24%, 67% and 92% of subjects had an antral volume below 20 mL at 60, 120 and 150 min, respectively. 81% of patients had a Boston score equal to 2 or 3 in each colonic segment. No adverse events leading to treatment discontinuation were reported.CONCLUSION: Gastric volume evaluation appeared to be a simple and reliable method for the assessment of gastric emptying. Data allow considering the NaP tablets bowel preparation in the morning of the procedure and confirming that gastric emptying is achieved after two hours, allowing general anaesthesia.

Transjugular intrahepatic portosystemic shunt as bridge-to-surgery in refractory gastric antral vascular ectasia

Gastric antral vascular ectasia(GAVE) may cause gastrointestinal bleeding(GIB). The treatment of GAVE relies on endoscopic approaches such as electrocoagulation(argon plasma coagulation, laser therapy, heater probe therapy, radiofrequency ablation), cryotherapy, and band ligation. In refractory cases, antrectomy may be considered. In the event of an associated cirrhosis and portal hypertension, it has been suggested that antrectomy could be an option, provided the mortality risk isn't considered too great. We report the case of a 67-year-old cirrhotic patient who presented with GAVE related GIB, unresponsive to multiple endoscopic treatments. The patient had a good liver function(model for end-stage disease 10). After a multidisciplinary meeting, a transjugular intrahepatic portosystemic shunt(TIPS) procedure was performed, in order to treat the cirrhosis associated ascites. The outcome was successful. An antrectomy was then performed, with no recurrence of GIB and no transfusion need during three months of follow up. In this case, the TIPS procedure achieved a complete ascites regression, allowing a safer surgical treatment of the GAVE-related GIB.

Nuclear magnetic resonance based metabolomics and liverdiseases:Recent advances and future clinical applications

Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification.It is an"omics"technique that is situated downstream of genomics,transcriptomics and proteomics.Metabolomics is recognized as a promising technique in the field of systems biology for the evaluation of global metabolic changes.During the last decade,metabolomics approaches have become widely used in the study of liver diseases for the detection of early biomarkers and altered metabolic pathways.It is a powerful technique to improve our pathophysiological knowledge of various liver diseases.It can be a useful tool to help clinicians in the diagnostic process especially to distinguish malignant and non-malignant liver disease as well as to determine the etiology or severity of the liver disease.It can also assess therapeutic response or predict drug induced liver injury.Nevertheless,the usefulness of metabolomics is often not understood by clinicians,especially the concept of metabolomics profiling or fingerprinting.In the present work,after a concise description of the different techniques and processes used in metabolomics,we will review the main research on this subject by focusing specifically on in vitro proton nuclear magnetic resonance spectroscopy based metabolomics approaches in human studies.We will first consider the clinical point of view enlighten physicians on this new approach and emphasis its future use in clinical"routine".

Exosomal microRNAs as a potential therapeutic strategy in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the fifth most com-mon cancer and the second cause of cancer-related death worldwide. The incidence of HCC is constantly increasing in correlation with the rise in diabetes and obesity, arguing for an urgent need for new developments in the treatment of this lethal cancer. Exosomes are small double-membrane vesicles loaded with distinct cargos, particularly small non-coding RNAs called microRNAs, representative of each donor cell and secreted to affect the features of neighboring cells or recipient cells located further away, like in the case of metastasis. A better understanding of the role of exosomes with a microRNA signature in cancer pathogenesis gave rise to the concept of their use as a noninvasive diagnostic biomarker and in the treatment of cancer, including HCC. In this communication, we review recent works that demonstrate that hepatic stellate cells establish an epigenetic communication with liver cancer cells, which affects their pro-malignant features. If naturally secreted patient-derived exosomes show major limitations concerning their clinical use, bio-engineered exosome mimetics that incorporate controlled components and exhibit no protumoral properties could be promising carriers for the treatment of liver cancers, which is the organ preferentially targeted by systemic injection of exosomes.

MicroRNA-feedback loop as a key modulator of liver tumorigenesis and inflammation

A recent work of Iliopoulos et al published in Cell highlighted a circuit orchestrated by microRNAs (miRNAs) that results in liver tumorigenesis and inflammation. This feedback loop, governed by miR-24 and miR-629, promotes a hepatocyte nuclear factor-4α transient inhibition resulting in miR-124 induction and signal transducer and activator of transcription 3 activation. These promising data support the use of miRNA mimics or inhibitors as potent therapeutic approaches in liver cancer.

An Optimal Weight Method for CT Image Denoising

This paper proposes a novel exemplar- based method for reducing noise in computed tomography （CT） images. In the proposed method, denoising is performed on each block with the help of a given database of standard image blocks. For each noisy block, its denoised version is the best sparse positive linear combination of the blocks in the database. We formulate the problem as a constrained optimization problem such that the solution is the denoised block. Experimental results demonstrate the good performance of the proposed method over current state-of-the-art denoising methods, in terms of both objective and subjective evaluations.

New insights into sodium transport regulation in the distal nephron:Role of G-protein coupled receptors

The renal handling of Na^+ balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part(i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na^+ excretion and are the target of many different regulatory processes that modulate Na^+ retention more or less efficiently. G-protein coupled receptors(GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na^+ absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na^+ excretion, this review also highlights the complexity of these different pathways, and the connections between them.

Next generation sequencing, inter-tumor heterogeneity and prognosis of hepatitis B related hepatocellular carcinoma

Hepatocellular carcinoma（HCC）is one of the leading causes of cancer related death in Asia and Africa（1）.It reflects the high burden of hepatitis B virus（HBV）infection in these areas.Curative treatments of HCC as radiofrequency ablation and resection are impaired by a high rate of tumor recurrence.However,most of the time,HCC is frequently diagnosed at advanced stages where only

Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.

Sorafenib Acts through VEGFR-2 Inhibition in a Metastatic Clear-Cell Sarcoma of the Kidney

We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.

Field report:Sailing around the exhumed roots of the Mesozoic Patagonian paleo-accretionary wedge(Diego de Almagro Island,Chile)

We undertook a boat expedition to explore the geological framework of a very remote, lesser-known island, in the Chilean Patagonia: the Diego de Almagro Island(latitude S51°330'). This uninhabited, ca.400 km^2 Island is one of the very rare exposures of the Mesozoic accretionary subduction complex along the Chilean margin. Unstable weather, strong winds, steep topography, and very dense vegetation make an on-land mission difficult. Careful preparation based on high-resolution satellite images is advised to optimize shore access and minimize risks of injury. Despite a relatively important degree of regional reequilibration of metamorphic assemblages due to sluggish exhumation through the forearc crust, our results have shown that the island is composed of a nappe stack of ocean-floor derived slivers of metasedimentary units that exhibit very different pressure-temperature-time paths during burial by subduction under the Chilean margin and subsequent exhumation. These rocks are witness to a complex thermal evolution of the subduction zone between Jurassic and Cretaceous times from granulite facies to blueschist facies conditions as well as multiple episodes of accretion at ca. 35 -40 km in depth for almost100 Ma over the Mesozoic era.

Age-related modifications of macrophages influenced by “inflammageing”in graft vs. host disease

Most studies focus on the adaptive immune cells in the GVHD pathogenesis,while little is known about innate immune cells in GVHD occurrence and development,especially macrophages.Meanwhile,a higher incidence of graft versus host disease(GVHD)is also found in the elderly patients.Though advances have been made in the modification of macrophages influenced by the inflamm-ageing,there is still no review on the role of macrophages in GVHD and the association between GVHD and the altered macrophages by inflamm-ageing.In this review,we focus on the potential age-related modifications of macrophage in GVHD,which contributes to the change of morbidity and mortality of GVHD.Via literature review,we found that the infiltration of macrophages is associated with GVHD and macrophages are modified in inflamm-ageing state,including the proliferation,migration,phagocytosis,antigen presentation,interaction with other immune cells,and pro-fibrosis.We suppose that altered macrophage functions in inflamm-ageing state contribute to GVHD in elderly patients.

Novel Active Contour Model for Image Segmentation Based on Local Fuzzy Gaussian Distribution Fitting

A novel active contour model is proposed, which incorporates local information distributions in a fuzzy energy function to effectively deal with the intensity inhomogeneity. Moreover, the proposed model is convex with respect to the variable which is used for extracting the contour. This makes the model independent on the initial condition and suitable for an automatic segmentation. Furthermore, the energy function is minimized in a computationally efficient way by calculating the fuzzy energy alterations directly. Experiments are carried out to prove the performance of the proposed model over some existing methods. The obtained results confirm the efficiency of the method.

Effects of some parameters on the divertor plasma sheath characteristics and fuel retention in castellated tungsten tile gaps

Castellation of plasma facing components is foreseen as the best solution for ensuring the lifetime of future fusion devices. However, the gaps between the resulting surface elements can increase fuel retention and complicate fuel removal issues. To know how the fuel is retained inside the gaps, the plasma sheath around the gaps needs to be understood first. In this work, a kinetic model is used to study plasma characteristics around the divertor gaps with the focus on the H＋ penetration depth inside the poloidal gaps, and a rate-theory model is coupled to simulate the hydrogen retention inside the tungsten gaps. By varying the magnetic field strength and plasma temperature, we find that the H＋ cyclotron radius has a significant effect on the penetration depth. Besides, the increase of magnetic field inclination angle can also increase the penetration depth. It is found in this work that parameters as well as the penetration depth strongly affect fuel retention in tungsten gaps.