The rapidly growing field of functional,molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a"digital biopsy"for i...The rapidly growing field of functional,molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a"digital biopsy"for in vivo study of liver pathophysiology.To foster the application of bio-imaging in clinical and translational research,there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver.It can be hoped that the combination of digital,liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies,diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer.A group of experts of different disciplines(Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver,Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure)discussed criteria,methods and guidelines for facilitating the requisite application of data collection.This manuscript provides a multi-Author review of the issue with special focus on fatty liver.展开更多
Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a sm...Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a small portion of DFUsmay undergomalignant transformation.The subsequentmalignancies are skin cancers such as squamous cell carcinoma(SCC),basal cell carcinoma,or melanoma.Understanding the pathophysiology of DFUs and themolecular and clinical determinants that contribute to theirpotentialmalignant transformationif crucial for clinical management.Chronic inflammation,dysregulation of cytokine signaling,faulty immune surveillance,and impaired wound healing all play a role in creating a tumor-permissive environment for the diabetic foot.This review highlights molecularmechanisms driving this transformation,including,vascular endothelial growth factor(VEGF)and plateletderived growth factor(PDGF)pathway dysregulation,hypoxia-inducible factor 1-alpha(HIF-1α)mediated angiogenic signaling,chronic osteomyelitis,and oxidative stress,which can collectively promote progression to malignancies,most notably cutaneous squamous cell carcinoma.Classic examples like Marjolin’s ulcer demonstrate how chronic injury can drive carcinogenesis,reinforcing the importance of vigilant DFU management.Connecting findings across clinical reports and mechanistic studies reveals that understandingDFUcarcinogenesis is essential for earlier detection,informed targeted treatment,and improved patient outcomes.展开更多
Colorectal cancer(CRC)is one of the most common cancer worldwide and results from the accumulation of mutations and epimutations in colonic mucosa cells ultimately leading to cell proliferation and metastasis.Unfortun...Colorectal cancer(CRC)is one of the most common cancer worldwide and results from the accumulation of mutations and epimutations in colonic mucosa cells ultimately leading to cell proliferation and metastasis.Unfortunately,CRC prognosis is still poor and the search of novel diagnostic and prognostic biomarkers is highly desired to prevent CRC-related deaths.The present article aims to summarize the most recent findings concerning the use of either genetic or epigenetic(mainly related to DNA methylation)biomarkers for CRC diagnosis,prognosis,and response to treatment.Recent large-scale DNA methylation studies suggest that CRC can be divided into several subtypes according to the frequency of DNA methylation and those of mutations in key CRC genes,and that this is reflected by different prognostic outcomes.Increasing evidence suggests that the analysis of DNA methylation in blood or fecal specimens could represent a valuable non-invasive diagnostic tool for CRC.Moreover,a broad spectrum of studies indicates that the inter-individual response to chemotherapeutic treatments depends on both epigenetic modifications and genetic mutations occurring in colorectal cancer cells,thereby opening the way for a personalized medicine.Overall,combining genetic and epigenetic data might represent the most promising tool for a proper diagnostic,prognostic and therapeutic approach.展开更多
While the peripheral nervous system has regenerative ability,restoration of sufficient function remains a challenge.Vimentin has been shown to be localized in axonal growth fronts and associated with nerve regeneratio...While the peripheral nervous system has regenerative ability,restoration of sufficient function remains a challenge.Vimentin has been shown to be localized in axonal growth fronts and associated with nerve regeneration,including myelination,neuroplasticity,kinase signaling in nerve axoplasm,and cell migration;however,the mechanisms regulating its expression within Schwann cell（SC） remain unexplored.The aim of this study was to profile the spatial and temporal expression profile of micro RNA（mi RNA） in a regenerating rat sciatic nerve after transection,and explore the potential role of mi R-138-5 p targeting vimentin in SC proliferation and migration.A rat sciatic nerve transection model,utilizing a polyethylene nerve guide,was used to investigate mi RNA expression at 7,14,30,60,and 90 days during nerve regeneration.Relative levels of mi RNA expression were determined using microarray analysis and subsequently validated with quantitative real-time polymerase chain reaction.In vitro assays were conducted with cultured Schwann cells transfected with mi RNA mimics and assessed for migratory and proliferative potential.The top seven dysregulated mi RNAs reported in this study have been implicated in cell migration elsewhere,and GO and KEGG analyses predicted activities essential to wound healing.Transfection of one of these,mi RNA-138-5 p,into SCs reduced cell migration and proliferation.mi R-138-5 p has been shown to directly target vimentin in cancer cells,and the luciferase assay performed here in rat Schwann cells confirmed it.These results detail a role of mi R-138-5 p in rat peripheral nerve regeneration and expand on reports of it as an important regulator in the peripheral nervous system.展开更多
BACKGROUND Recent evidences have shown a relationship between prion protein(PrPc)expression and pancreatic ductal adenocarcinoma(PDAC).Indeed,PrPc could be one of the markers explaining the aggressiveness of this tumo...BACKGROUND Recent evidences have shown a relationship between prion protein(PrPc)expression and pancreatic ductal adenocarcinoma(PDAC).Indeed,PrPc could be one of the markers explaining the aggressiveness of this tumor.However,studies investigating the specific compartmentalization of increased PrPc expression within PDAC cells are lacking,as well as a correlation between ultrastructural evidence,ultrastructural morphometry of PrPc protein and clinical data.These data,as well as the quantitative stoichiometry of this protein detected by immuno-gold,provide a significant advancement in understanding the biology of disease and the outcome of surgical resection.AIM To analyze quantitative stoichiometry and compartmentalization of PrPc in PDAC cells and to correlate its presence with prognostic data METHODS Between June 2018 and December 2020,samples from pancreatic tissues of 45 patients treated with pancreatic resection for a preoperative suspicion of PDAC at our Institution were collected.When the frozen section excluded a PDAC diagnosis,or the nodules were too small for adequate sampling,patients were ruled out from the present study.Western blotting was used to detect,quantify and compare the expression of PrPc in PDAC and control tissues,such as those of non-affected neighboring pancreatic tissue of the same patient.To quantify the increase of PrPc and to detect the subcellular compartmentalization of PrPc within PDAC cells,immuno-gold stoichiometry within specific cell compartments was analyzed with electron microscopy.Finally,an analysis of quantitative PrPc expression according to prognostic data,such as cancer stage,recurrence of the disease at 12 mo after surgery and recurrence during adjuvant chemotherapy was made.RESULTS The amount of PrPc within specimen from 38 out of 45 patients was determined by semi-quantitative analysis by using Western blotting,which indicates that PrPc increases almost three-fold in tumor pancreatic tissue compared with healthy pancreatic regions[242.41±28.36 optical density(OD)vs 95±17.40 OD,P<0.0001].Quantitative morphometry carried out by using immuno-gold detection at transmission electron microscopy confirms an increased PrPc expression in PDAC ductal cells of all patients and allows to detect a specific compartmentalization of PrPc within tumor cells.In particular,the number of immuno-gold particles of PrPc was significantly higher in PDAC cells respect to controls,when considering the whole cell(19.8±0.79 particles vs 9.44±0.45,P<0.0001).Remarkably,considering PDAC cells,the increase of PrPc was higher in the nucleus than cytosol of tumor cells,which indicates a shift in PrPc compartmentalization within tumor cells.In fact,the increase of immuno-gold within nuclear compartment exceeds at large the augment of PrPc which was detected in the cytosol(nucleus:12.88±0.59 particles vs 5.12±0.32,P<0.0001;cytosol:7.74.±0.44 particles vs 4.3±0.24,P<0.0001).RESULTS In order to analyze the prognostic impact of PrPc,we found a correlation between PrPc expression and cancer stage according to pathology results,with a significantly higher expression of PrPc for advanced stages.Moreover,24 patients with a mean follow-up of 16.8 mo were considered.Immuno-blot analysis revealed a significantly higher expression of PrPc in patients with disease recurrence at 12 mo after radical surgery(360.71±69.01 OD vs 170.23±23.06 OD,P=0.023),also in the subgroup of patients treated with adjuvant CT(368.36±79.26 OD in the recurrence group vs 162.86±24.16 OD,P=0.028),which indicates a correlation with a higher chemo-resistance.CONCLUSION Expression of PrPc is significantly higher in PDAC cells compared with control,with the protein mainly placed in the nucleus.Preliminary clinical data confirm the correlation with a poorer prognosis.展开更多
Nosocomial infections affect implanted medical devices and greatly challenge their functional outcomes,becoming sometimes life threatening for the patients.Therefore,aggressive antibiotic therapies are administered,wh...Nosocomial infections affect implanted medical devices and greatly challenge their functional outcomes,becoming sometimes life threatening for the patients.Therefore,aggressive antibiotic therapies are administered,which often require the use of last-resort drugs,if the infection is caused by multi-drug-resistant bacteria.Reducing the risk of bacterial contamination of medical devices in the hospitals has thus become an emerging issue.Promising routes to control these infections are based on materials provided with intrinsic bactericidal properties(i.e.,chemical action)and on the design of surface coatings able to limit bacteria adhesion and fouling phenomena(i.e.,physical action),thus preventing bacterial biofilm formation.Here,we report the development and validation of coatings made of layer-by-layer deposition of electrospun poly(vinylidene fluoride-co-trifluoro ethylene)P(VDF-TrFE)fibers with controlled orientations,which ultimately gave rise to antifouling surfaces.The obtained 10-layer surface morphology with 90°orientation fibers was able to efficiently prevent the adhesion of bacteria,by establishing a superhydrophobic-like behavior compatible with the Cassie-Baxter regimen.Moreover,the results highlighted that surface wettability and bacteria adhesion could be controlled using fibers with diameter comparable to bacteria size(i.e.,achievable via electrospinning process),by tuning the intra-fiber spacing,with relevant implications in the future design of biomedical surface coatings.展开更多
Hepatocellular carcinoma,the most common primary liver cancer,in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages.Although,surgical resection,ablation,liver transplant,and l...Hepatocellular carcinoma,the most common primary liver cancer,in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages.Although,surgical resection,ablation,liver transplant,and locoregional therapies are available for early stages;however,there are yet no effective treatment for advanced and recurrent tumors.Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression.However,still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment.At present,the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy,immune checkpoint therapy,adoptive cell transfer therapy,and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells.This review discusses the recent key development,the basis of drug resistance,immune evasion,immune tolerance,the available therapies based on stage of the tumor,and the ongoing clinical trials on immune checkpoint inhibitor therapy,adoptive cell transfer therapy,oncolytic viral vaccine therapy,and combination therapy.展开更多
BACKGROUND Artificial intelligence in radiology has the potential to assist with the diagnosis,prognostication and therapeutic response prediction of various cancers.A few studies have reported that texture analysis c...BACKGROUND Artificial intelligence in radiology has the potential to assist with the diagnosis,prognostication and therapeutic response prediction of various cancers.A few studies have reported that texture analysis can be helpful in predicting the response to chemotherapy for colorectal liver metastases,however,the results have varied.Necrotic metastases were not clearly excluded in these studies and in most studies the full range of texture analysis features were not evaluated.This study was designed to determine if the computed tomography(CT)texture analysis results of non-necrotic colorectal liver metastases differ from previous reports.A larger range of texture features were also evaluated to identify potential new biomarkers.AIM To identify potential new imaging biomarkers with CT texture analysis which can predict the response to first-line cytotoxic chemotherapy in non-necrotic colorectal liver metastases(CRLMs).METHODS Patients who presented with CRLMs from 2012 to 2020 were retrospectively selected on the institutional radiology information system of our private radiology practice.The inclusion criteria were non-necrotic CRLMs with a minimum size of 10 mm(diagnosed on archived 1.25 mm portal venous phase CT(FOLFOX,FOLFIRI,FOLFOXIRI,CAPE-OX,CAPE-IRI or capecitabine).The final study cohort consisted of 29 patients.The treatment response of the CRLMs was classified according to the RECIST 1.1 criteria.By means of CT texture analysis,various first and second order texture features were extracted from a single nonnecrotic target CRLM in each responding and non-responding patient.Associations between features and response to chemotherapy were assessed by logistic regression models.The prognostic accuracy of selected features was evaluated by using the area under the curve.RESULTS There were 15 responders(partial response)and 14 non-responders(7 stable and 7 with progressive disease).The responders presented with a higher number of CRLMs(P=0.05).In univariable analysis,eight texture features of the responding CRLMs were associated with treatment response,but due to strong correlations among some of the features,only two features,namely minimum histogram gradient intensity and long run low grey level emphasis,were included in the multiple analysis.The area under the receiver operating characteristic curve of the multiple model was 0.80(95%CI:0.64 to 0.96),with a sensitivity of 0.73(95%CI:0.48 to 0.89)and a specificity of 0.79(95%CI:0.52 to 0.92).CONCLUSION Eight first and second order texture features,but particularly minimum histogram gradient intensity and long run low grey level emphasis are significantly correlated with treatment response in non-necrotic CRLMs.展开更多
AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional co...AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design.We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units.Information in the case report forms included main demographic data,blood chemistry data,viral hepatitis markers,instrumental evaluations,and eligibility for treatment or ongoing therapy and liver transplantation.RESULTS Of 4015 chronic viral hepatitis patients,1096(27.3%)were HBV infected.The case report form was correctly completed for only 833 patients(64%males,36%females;mean age 50.1±15.4).Of these HBV-infected patients,73%were Caucasian,21%Asian,4%Central African,1%North African and 1%American.Stratifying patients by age and nationality,we found that 21.7%of HBV-infected patients were aged<34 years(only 2.8%were Italian).The most represented routes of transmission were nosocomial/dental procedures(23%),mother-to-child(17%)and sexual transmission(12%).The most represented HBV genotypes were D(72%)and A(14%).Of the patients,24.7%of patients were HBe Ag positive,and 75.3%were HBe Ag negative.Of the HBV patients 7%were anti-HDV positive.In the whole cohort,26.9%were cirrhotic(35.8%aged<45 years),and 47%were eligible for or currently undergoing treatment,of whom 41.9%were cirrhotic.CONCLUSION Only 27.3%of chronic viral hepatitis patients were HBV infected.Our results provide evidence of HBV infection in people aged<34 years,especially in the foreign population not protected by vaccination.In our cohort of patients,liver cirrhosis was also found in young adults.展开更多
Colorectal cancer(CRC) represents one of the most relevant causes of morbidity and mortality in Western societies. CRC screening is actually based on faecal occult blood testing, and optical colonoscopy still remains ...Colorectal cancer(CRC) represents one of the most relevant causes of morbidity and mortality in Western societies. CRC screening is actually based on faecal occult blood testing, and optical colonoscopy still remains the gold standard screening test for cancer detection. However, computed tomography colonography(CT colonography) constitutes a reliable, minimally-invasive method to rapidly and effectively evaluate the entire colon for clinically relevant lesions. Furthermore, even if the benefits of its employment in CRC mass screening have not fully established yet, CT colonography may represent a reasonable alternative screening test in patients who cannot undergo or refuse colonoscopy. Therefore, the purpose of our review is to illustrate the most updated recommendations on methodology and the current clinical indications of CT colonography, according to the data of the existing relevant literature.展开更多
BACKGROUND Walled-off pancreatic necrosis (WOPN) is a late complication of acute pancreatitis. The management of a WOPN depends on its location and on patient's symptoms. Trans-gastric drainage and debridement of ...BACKGROUND Walled-off pancreatic necrosis (WOPN) is a late complication of acute pancreatitis. The management of a WOPN depends on its location and on patient's symptoms. Trans-gastric drainage and debridement of WOPN represents an important surgical treatment option for selected patients. The da Vinci surgical System has been developed to allow an easy, minimally invasive and fast surgery, also in challenging abdominal procedures. We present here a case of a WOPN treated with a robotic trans-gastric drainage using the da Vinci Xi. CASE SUMMARY A 63-year-old man with an episode of acute necrotizing pancreatitis was referred to our center. Six wk after the acute episode the patient developed a walled massive fluid collection, with an extensive pancreatic necrosis, causing obstruction of the gastrointestinal tract. The patient underwent a robotic transgastric drainage and debridement of the WOPN performed with the da Vinci Xi platform. Firstly, an anterior ideal gastrotomy was carried out, guided by intraoperative ultrasound (US)-scan using the TilePro? function. Then, through the gastrotomy, the best location for drainage on the posterior gastric wall was again US-guided identified. The anastomosis between the posterior gastric wall and the walled-off necrosis wall was carried out with the new EndoWrist stapler with vascular cartridge. Debridement and washing of the cavity through the anastomosis were performed. Finally, the anterior gastrotomy was closed and the cholecystectomy was performed. The postoperative course was uneventful and a post-operative computed tomography-scan showed the collapse of the fluid collection. CONCLUSION In selected cases of WOPN the da Vinci Surgical System can be safely used as a valid surgical treatment option.展开更多
BACKGROUND The response to chemotherapy treatment of patients with pancreatic ductal adenocarcinoma(PDAC)is difficult to predict and the identification of patients who most likely will benefit from aggressive chemothe...BACKGROUND The response to chemotherapy treatment of patients with pancreatic ductal adenocarcinoma(PDAC)is difficult to predict and the identification of patients who most likely will benefit from aggressive chemotherapy approaches is crucial.The concept of personalized medicine has emerged in the last years with the objective to tailor the medical treatment to the individual characteristics of each patient,and particularly to the tumor biology of each patient.The need for invivo xenotransplantation models for cancer patients has increased exponentially,and for this reason zebrafish avatars have gained popularity.Preliminary studies were conducted also with PDAC tissue.AIM To develop a simple,not expensive,diffusible zebrafish embryo model as avatar for patients affected by PDAC.METHODS Tumor tissue was taken from the surgical specimen by the histopathologist.After its fragmentation into small pieces,they are stained with CM-Dil.Small pieces of stained tissue were transplanted into the yolk of wt AB zebrafish embryos with a glass capillary needle.Embryos were incubated at 35°C in E3 medium supplemented with 1%Pen/Strep in the presence or absence of drugs for the following days in respect of the treatment plan(Gemcitabine;Gemcitabine and Oxaliplatin;Gemcitabine and nab-Paclitaxel;5-Fluorouracil and Folinic acid and Oxaliplatin and Irinotecan).The response of zebrafish xenografts to the chemotherapy options has been analyzed by monitoring the fluorescent stained area at 2 h post injection(hpi),1 d and 2 d post injection(dpi).In each time point,the mean size of the stained area was measured by ImageJ and it was normalized with respect to the 1 dpi time point mean relative tumor area(RTA).We evaluated the effect of the chemotherapy exposition comparing the mean RTA of each treated subgroup and the control group and evaluating the percentage reduction of the mean RTA by comparing each treated subgroup with the control group.RESULTS Between July 2018 and October 2019,a total of 15 patients with pancreatic cancer were prospectively enrolled.In all cases,it was possible to take a fragment of the tumor from the surgical specimen for the xenotransplantation in the zebrafish embryos.The histological examination confirmed the presence of a PDAC in all cases.In absence of chemotherapy(control group),over time the Dil-stained area showed a statistically significant increase in all cases.A statistically significant reduction of the mean RTA in the treated subgroups for at least one chemotherapy scheme was reported in 6/15(40%)cases.The analysis of the percentage reduction of the RTA in treated subgroups in comparison to the control group revealed the presence of a linear relationship in each subgroup between the percentage reduction of the RTA and the number of cases reporting each percentage threshold considered for the analysis.CONCLUSION Our model seems to be effective for the xenotransplantation of PDAC tissue and evaluation of the effect of each chemotherapy scheme on the xenotransplanted tumor tissue.展开更多
BACKGROUND‘Splenosis’is defined as the autotransplantation of splenic tissue following trauma or surgery,usually in the form of intraperitoneal nodules.The proliferation of imaging techniques has resulted in increas...BACKGROUND‘Splenosis’is defined as the autotransplantation of splenic tissue following trauma or surgery,usually in the form of intraperitoneal nodules.The proliferation of imaging techniques has resulted in increased unexpected discoveries of splenosis nodules,and achieving a differential diagnosis can be challenging.Nuclear medicine studies have been playing an increasingly important role in this process,but the clinical significance of asymptomatic nodules remains uncertain.CASE SUMMARY We present a case of pelvic splenosis in a 73-year-old man diagnosed 56 years after a splenectomy during a computed tomography(CT)follow-up for B-cell lymphoma,presenting intense contrast enhancement of an 18 mm nodule in the right recto-vesical space.18F-fluorodeoxyglucose demonstrated weak metabolic activity.Since histological diagnosis was deemed necessary,the nodule was easily removed with robotically assisted laparoscopy,together with another 6 mm left a paracolic lesion.The latter was previously undiagnosed but retrospectively visible on the CT scan.CONCLUSION In a patient requiring differential diagnosis of splenosis nodules from lymphomarecurrence, the robotic approach provided a safe en bloc removal with shorthospitalization. The Da Vinci Xi robot was particularly helpful because its opticscan be introduced from all ports, facilitating visualization and lysis of multipleintra-abdominal adhesions.展开更多
Worldwide epidemiological reports assert that drinking water is a source for infections and Legionella control represents a critical issue in healthcare settings. Chemical disinfections of water networks are control m...Worldwide epidemiological reports assert that drinking water is a source for infections and Legionella control represents a critical issue in healthcare settings. Chemical disinfections of water networks are control measures that need to be fine-tuned to obtain satisfactory results in large buildings over prolonged time periods. Aim of study is the evaluation of the effect of anolyte and chlorine dioxide, applied in two different hot water networks of a nursing home to manage Legionella risk. Nursing home has two buildings (A and B), with the same point of aqueduct water entrance. From June 2016, following a shock chlorination, the continuous disinfections with chlorine dioxide and anolyte were applied in hot networks of building A and B, respectively. Hot water was sampled at the central heating system and at two points of use for Legionella research, while chemical tests of manganese (Mn), iron (Fe), zinc (Zn) and trihalomethanes compounds (THM) were implemented to evaluate the disinfection by-products presence. Before chlorination Legionella pneumophila sg1 was recovered with a mean count of 2.4 × 104 CFU/L, while chemical compounds concentrations were within the law limits (Directive 98/83/EC). Then the disinfections Legionella was not recovered in both hot water plants. After the disinfection with chlorine dioxide (from June 2016 to May 2018), a statistically significant increase of iron, zinc and THM concentrations was detected in building A (p = 0.012;p = 0.004;p = 0.008). Both disinfectants appear effective against Legionella spp. growth in water network, but anolyte ensures a lower disinfection by-products release.展开更多
AIM:To evaluate the direct and indirect biocompatibility of Filtek Silorane on human gingival fibroblastic cells.METHODS:Sixty-three standardized cylindrical specimens(8 mm diameter and 2 mm thickness)of restorative m...AIM:To evaluate the direct and indirect biocompatibility of Filtek Silorane on human gingival fibroblastic cells.METHODS:Sixty-three standardized cylindrical specimens(8 mm diameter and 2 mm thickness)of restorative material were prepared using a light emitting diode-curing unit.The sample were built up in one increment and divided in 2 groups.In the first group,21samples(unpolished samples)were left without a specific polishing procedure;in the second one,42 samples(polished samples)were polished with 4 different grains of discs.Fibroblast cultures,obtained from gingiva of 2 subjects without systemic and oral disease,were used to assess the direct and indirect biocompatibility.Cells cultured for 48 h in normal culture medium were used as a control.RESULTS:The scanning electron microscope observations of fibroblasts cultured on the silorane samples,either polished or unpolished,confirmed the good biocompatibility of the material,favouring the cellular spreading.3-dimethylthiazol-2,5-diphenyltetrazolium bromide tests showed a significant reduction(P<0.01)of gingival fibroblasts viability cultured both in polished samples(90.05%±19.00%)and unpolished samples(78.15%±11.00%)compared with the control.Cells growth in medium conditioned with the samples for 1 wk showed a significant viability reduction(P<0.01)compared to the control.A reduction of cell viability was observed even in the groups containing the material for 3 wk(polished:89.45%±10.00%;unpolished:65.97%±10.00%),even if the cytotoxicity was reduced after this long time exposure.CONCLUSION:Although the poor chromatic availability of this material remains a big limit that restricts its use to posterior sectors,the silorane-based material can be considered an option to perform restorations when aesthetic demands are not the priority,such as the展开更多
Gastroparesis(Gp)is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction.Although this condition has been reported in the literature since the mid-1900s,only recently ...Gastroparesis(Gp)is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction.Although this condition has been reported in the literature since the mid-1900s,only recently has there been renewed clinical and scientific interest in this disease,which has a potentially great impact on the quality of life.The aim of this review is to explore the pathophysiological,diagnostic and therapeutical aspects of Gp according to the most recent evidence.A comprehensive online search for Gp was carried out using MEDLINE and EMBASE.Gp is the result of neuromuscular abnormalities of the gastric motor function.There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes.As regards diagnostic approach,99-Technetium scintigraphy is currently considered to be the gold standard for Gp.Its limits are a lack of standardization and a mild risk of radiation exposure.The C13 breath testing is a valid and safe alternative method.13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits.The wireless motility capsule is a promising technique,but its use is limited by costs and scarce availability in many countries.Finally,therapeutic strategies are related to the clinical severity of Gp.In mild and moderate Gp,dietary modification and prokinetic agents are generally sufficient.Metoclopramide is the only drug approved by the Food and Drug Administration for Gp.However,other older and new prokinetics and antiemetics can be considered.As a second-line therapy,tricyclic antidepressants and cannabinoids have been proposed.In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed.In drug-unresponsive Gp patients some alternative strategies(endoscopic,electric stimulation or surgery)are available.展开更多
Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabet...Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus(T1DM) and T2 DM. T2 DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1 DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2 DM and chronic hepatitis C(CHC) infection. The processes through which CHC is associated with T2 DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immunemediated mechanisms. Few data have been reported on the association of CHC and T1 DM and reports on the potential association between T1 DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoim-munity and in certain cases lead to the development of T1 DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with nondiabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effec-tive programmes for the surveillance and treatment of diabetic CHC patients.展开更多
Gastroesophageal reflux disease(GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing...Gastroesophageal reflux disease(GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry(HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h p H-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and p H monitoring can detect acid and non-acid reflux events. Endo FLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal p H-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.展开更多
Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy production.They are particularly abundant in tissues with h...Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy production.They are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.展开更多
基金Supported by the Italian Ministry of Health Project,No.RF-2010-2314264
文摘The rapidly growing field of functional,molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a"digital biopsy"for in vivo study of liver pathophysiology.To foster the application of bio-imaging in clinical and translational research,there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver.It can be hoped that the combination of digital,liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies,diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer.A group of experts of different disciplines(Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver,Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure)discussed criteria,methods and guidelines for facilitating the requisite application of data collection.This manuscript provides a multi-Author review of the issue with special focus on fatty liver.
文摘Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a small portion of DFUsmay undergomalignant transformation.The subsequentmalignancies are skin cancers such as squamous cell carcinoma(SCC),basal cell carcinoma,or melanoma.Understanding the pathophysiology of DFUs and themolecular and clinical determinants that contribute to theirpotentialmalignant transformationif crucial for clinical management.Chronic inflammation,dysregulation of cytokine signaling,faulty immune surveillance,and impaired wound healing all play a role in creating a tumor-permissive environment for the diabetic foot.This review highlights molecularmechanisms driving this transformation,including,vascular endothelial growth factor(VEGF)and plateletderived growth factor(PDGF)pathway dysregulation,hypoxia-inducible factor 1-alpha(HIF-1α)mediated angiogenic signaling,chronic osteomyelitis,and oxidative stress,which can collectively promote progression to malignancies,most notably cutaneous squamous cell carcinoma.Classic examples like Marjolin’s ulcer demonstrate how chronic injury can drive carcinogenesis,reinforcing the importance of vigilant DFU management.Connecting findings across clinical reports and mechanistic studies reveals that understandingDFUcarcinogenesis is essential for earlier detection,informed targeted treatment,and improved patient outcomes.
基金Supported by T Istituto Toscano Tumori(ITT)No.Prot.AOOGRT/325424/Q.80.110 16/12/2009,‘‘Correlation among epigenetic,environmental and genetic factors in colorectal carcinoma’’
文摘Colorectal cancer(CRC)is one of the most common cancer worldwide and results from the accumulation of mutations and epimutations in colonic mucosa cells ultimately leading to cell proliferation and metastasis.Unfortunately,CRC prognosis is still poor and the search of novel diagnostic and prognostic biomarkers is highly desired to prevent CRC-related deaths.The present article aims to summarize the most recent findings concerning the use of either genetic or epigenetic(mainly related to DNA methylation)biomarkers for CRC diagnosis,prognosis,and response to treatment.Recent large-scale DNA methylation studies suggest that CRC can be divided into several subtypes according to the frequency of DNA methylation and those of mutations in key CRC genes,and that this is reflected by different prognostic outcomes.Increasing evidence suggests that the analysis of DNA methylation in blood or fecal specimens could represent a valuable non-invasive diagnostic tool for CRC.Moreover,a broad spectrum of studies indicates that the inter-individual response to chemotherapeutic treatments depends on both epigenetic modifications and genetic mutations occurring in colorectal cancer cells,thereby opening the way for a personalized medicine.Overall,combining genetic and epigenetic data might represent the most promising tool for a proper diagnostic,prognostic and therapeutic approach.
文摘While the peripheral nervous system has regenerative ability,restoration of sufficient function remains a challenge.Vimentin has been shown to be localized in axonal growth fronts and associated with nerve regeneration,including myelination,neuroplasticity,kinase signaling in nerve axoplasm,and cell migration;however,the mechanisms regulating its expression within Schwann cell（SC） remain unexplored.The aim of this study was to profile the spatial and temporal expression profile of micro RNA（mi RNA） in a regenerating rat sciatic nerve after transection,and explore the potential role of mi R-138-5 p targeting vimentin in SC proliferation and migration.A rat sciatic nerve transection model,utilizing a polyethylene nerve guide,was used to investigate mi RNA expression at 7,14,30,60,and 90 days during nerve regeneration.Relative levels of mi RNA expression were determined using microarray analysis and subsequently validated with quantitative real-time polymerase chain reaction.In vitro assays were conducted with cultured Schwann cells transfected with mi RNA mimics and assessed for migratory and proliferative potential.The top seven dysregulated mi RNAs reported in this study have been implicated in cell migration elsewhere,and GO and KEGG analyses predicted activities essential to wound healing.Transfection of one of these,mi RNA-138-5 p,into SCs reduced cell migration and proliferation.mi R-138-5 p has been shown to directly target vimentin in cancer cells,and the luciferase assay performed here in rat Schwann cells confirmed it.These results detail a role of mi R-138-5 p in rat peripheral nerve regeneration and expand on reports of it as an important regulator in the peripheral nervous system.
基金by Tizzi Foundation and Arpa Foundation(www.fondazionearpa.it).
文摘BACKGROUND Recent evidences have shown a relationship between prion protein(PrPc)expression and pancreatic ductal adenocarcinoma(PDAC).Indeed,PrPc could be one of the markers explaining the aggressiveness of this tumor.However,studies investigating the specific compartmentalization of increased PrPc expression within PDAC cells are lacking,as well as a correlation between ultrastructural evidence,ultrastructural morphometry of PrPc protein and clinical data.These data,as well as the quantitative stoichiometry of this protein detected by immuno-gold,provide a significant advancement in understanding the biology of disease and the outcome of surgical resection.AIM To analyze quantitative stoichiometry and compartmentalization of PrPc in PDAC cells and to correlate its presence with prognostic data METHODS Between June 2018 and December 2020,samples from pancreatic tissues of 45 patients treated with pancreatic resection for a preoperative suspicion of PDAC at our Institution were collected.When the frozen section excluded a PDAC diagnosis,or the nodules were too small for adequate sampling,patients were ruled out from the present study.Western blotting was used to detect,quantify and compare the expression of PrPc in PDAC and control tissues,such as those of non-affected neighboring pancreatic tissue of the same patient.To quantify the increase of PrPc and to detect the subcellular compartmentalization of PrPc within PDAC cells,immuno-gold stoichiometry within specific cell compartments was analyzed with electron microscopy.Finally,an analysis of quantitative PrPc expression according to prognostic data,such as cancer stage,recurrence of the disease at 12 mo after surgery and recurrence during adjuvant chemotherapy was made.RESULTS The amount of PrPc within specimen from 38 out of 45 patients was determined by semi-quantitative analysis by using Western blotting,which indicates that PrPc increases almost three-fold in tumor pancreatic tissue compared with healthy pancreatic regions[242.41±28.36 optical density(OD)vs 95±17.40 OD,P<0.0001].Quantitative morphometry carried out by using immuno-gold detection at transmission electron microscopy confirms an increased PrPc expression in PDAC ductal cells of all patients and allows to detect a specific compartmentalization of PrPc within tumor cells.In particular,the number of immuno-gold particles of PrPc was significantly higher in PDAC cells respect to controls,when considering the whole cell(19.8±0.79 particles vs 9.44±0.45,P<0.0001).Remarkably,considering PDAC cells,the increase of PrPc was higher in the nucleus than cytosol of tumor cells,which indicates a shift in PrPc compartmentalization within tumor cells.In fact,the increase of immuno-gold within nuclear compartment exceeds at large the augment of PrPc which was detected in the cytosol(nucleus:12.88±0.59 particles vs 5.12±0.32,P<0.0001;cytosol:7.74.±0.44 particles vs 4.3±0.24,P<0.0001).RESULTS In order to analyze the prognostic impact of PrPc,we found a correlation between PrPc expression and cancer stage according to pathology results,with a significantly higher expression of PrPc for advanced stages.Moreover,24 patients with a mean follow-up of 16.8 mo were considered.Immuno-blot analysis revealed a significantly higher expression of PrPc in patients with disease recurrence at 12 mo after radical surgery(360.71±69.01 OD vs 170.23±23.06 OD,P=0.023),also in the subgroup of patients treated with adjuvant CT(368.36±79.26 OD in the recurrence group vs 162.86±24.16 OD,P=0.028),which indicates a correlation with a higher chemo-resistance.CONCLUSION Expression of PrPc is significantly higher in PDAC cells compared with control,with the protein mainly placed in the nucleus.Preliminary clinical data confirm the correlation with a poorer prognosis.
文摘Nosocomial infections affect implanted medical devices and greatly challenge their functional outcomes,becoming sometimes life threatening for the patients.Therefore,aggressive antibiotic therapies are administered,which often require the use of last-resort drugs,if the infection is caused by multi-drug-resistant bacteria.Reducing the risk of bacterial contamination of medical devices in the hospitals has thus become an emerging issue.Promising routes to control these infections are based on materials provided with intrinsic bactericidal properties(i.e.,chemical action)and on the design of surface coatings able to limit bacteria adhesion and fouling phenomena(i.e.,physical action),thus preventing bacterial biofilm formation.Here,we report the development and validation of coatings made of layer-by-layer deposition of electrospun poly(vinylidene fluoride-co-trifluoro ethylene)P(VDF-TrFE)fibers with controlled orientations,which ultimately gave rise to antifouling surfaces.The obtained 10-layer surface morphology with 90°orientation fibers was able to efficiently prevent the adhesion of bacteria,by establishing a superhydrophobic-like behavior compatible with the Cassie-Baxter regimen.Moreover,the results highlighted that surface wettability and bacteria adhesion could be controlled using fibers with diameter comparable to bacteria size(i.e.,achievable via electrospinning process),by tuning the intra-fiber spacing,with relevant implications in the future design of biomedical surface coatings.
文摘Hepatocellular carcinoma,the most common primary liver cancer,in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages.Although,surgical resection,ablation,liver transplant,and locoregional therapies are available for early stages;however,there are yet no effective treatment for advanced and recurrent tumors.Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression.However,still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment.At present,the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy,immune checkpoint therapy,adoptive cell transfer therapy,and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells.This review discusses the recent key development,the basis of drug resistance,immune evasion,immune tolerance,the available therapies based on stage of the tumor,and the ongoing clinical trials on immune checkpoint inhibitor therapy,adoptive cell transfer therapy,oncolytic viral vaccine therapy,and combination therapy.
文摘BACKGROUND Artificial intelligence in radiology has the potential to assist with the diagnosis,prognostication and therapeutic response prediction of various cancers.A few studies have reported that texture analysis can be helpful in predicting the response to chemotherapy for colorectal liver metastases,however,the results have varied.Necrotic metastases were not clearly excluded in these studies and in most studies the full range of texture analysis features were not evaluated.This study was designed to determine if the computed tomography(CT)texture analysis results of non-necrotic colorectal liver metastases differ from previous reports.A larger range of texture features were also evaluated to identify potential new biomarkers.AIM To identify potential new imaging biomarkers with CT texture analysis which can predict the response to first-line cytotoxic chemotherapy in non-necrotic colorectal liver metastases(CRLMs).METHODS Patients who presented with CRLMs from 2012 to 2020 were retrospectively selected on the institutional radiology information system of our private radiology practice.The inclusion criteria were non-necrotic CRLMs with a minimum size of 10 mm(diagnosed on archived 1.25 mm portal venous phase CT(FOLFOX,FOLFIRI,FOLFOXIRI,CAPE-OX,CAPE-IRI or capecitabine).The final study cohort consisted of 29 patients.The treatment response of the CRLMs was classified according to the RECIST 1.1 criteria.By means of CT texture analysis,various first and second order texture features were extracted from a single nonnecrotic target CRLM in each responding and non-responding patient.Associations between features and response to chemotherapy were assessed by logistic regression models.The prognostic accuracy of selected features was evaluated by using the area under the curve.RESULTS There were 15 responders(partial response)and 14 non-responders(7 stable and 7 with progressive disease).The responders presented with a higher number of CRLMs(P=0.05).In univariable analysis,eight texture features of the responding CRLMs were associated with treatment response,but due to strong correlations among some of the features,only two features,namely minimum histogram gradient intensity and long run low grey level emphasis,were included in the multiple analysis.The area under the receiver operating characteristic curve of the multiple model was 0.80(95%CI:0.64 to 0.96),with a sensitivity of 0.73(95%CI:0.48 to 0.89)and a specificity of 0.79(95%CI:0.52 to 0.92).CONCLUSION Eight first and second order texture features,but particularly minimum histogram gradient intensity and long run low grey level emphasis are significantly correlated with treatment response in non-necrotic CRLMs.
文摘AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design.We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units.Information in the case report forms included main demographic data,blood chemistry data,viral hepatitis markers,instrumental evaluations,and eligibility for treatment or ongoing therapy and liver transplantation.RESULTS Of 4015 chronic viral hepatitis patients,1096(27.3%)were HBV infected.The case report form was correctly completed for only 833 patients(64%males,36%females;mean age 50.1±15.4).Of these HBV-infected patients,73%were Caucasian,21%Asian,4%Central African,1%North African and 1%American.Stratifying patients by age and nationality,we found that 21.7%of HBV-infected patients were aged<34 years(only 2.8%were Italian).The most represented routes of transmission were nosocomial/dental procedures(23%),mother-to-child(17%)and sexual transmission(12%).The most represented HBV genotypes were D(72%)and A(14%).Of the patients,24.7%of patients were HBe Ag positive,and 75.3%were HBe Ag negative.Of the HBV patients 7%were anti-HDV positive.In the whole cohort,26.9%were cirrhotic(35.8%aged<45 years),and 47%were eligible for or currently undergoing treatment,of whom 41.9%were cirrhotic.CONCLUSION Only 27.3%of chronic viral hepatitis patients were HBV infected.Our results provide evidence of HBV infection in people aged<34 years,especially in the foreign population not protected by vaccination.In our cohort of patients,liver cirrhosis was also found in young adults.
文摘Colorectal cancer(CRC) represents one of the most relevant causes of morbidity and mortality in Western societies. CRC screening is actually based on faecal occult blood testing, and optical colonoscopy still remains the gold standard screening test for cancer detection. However, computed tomography colonography(CT colonography) constitutes a reliable, minimally-invasive method to rapidly and effectively evaluate the entire colon for clinically relevant lesions. Furthermore, even if the benefits of its employment in CRC mass screening have not fully established yet, CT colonography may represent a reasonable alternative screening test in patients who cannot undergo or refuse colonoscopy. Therefore, the purpose of our review is to illustrate the most updated recommendations on methodology and the current clinical indications of CT colonography, according to the data of the existing relevant literature.
文摘BACKGROUND Walled-off pancreatic necrosis (WOPN) is a late complication of acute pancreatitis. The management of a WOPN depends on its location and on patient's symptoms. Trans-gastric drainage and debridement of WOPN represents an important surgical treatment option for selected patients. The da Vinci surgical System has been developed to allow an easy, minimally invasive and fast surgery, also in challenging abdominal procedures. We present here a case of a WOPN treated with a robotic trans-gastric drainage using the da Vinci Xi. CASE SUMMARY A 63-year-old man with an episode of acute necrotizing pancreatitis was referred to our center. Six wk after the acute episode the patient developed a walled massive fluid collection, with an extensive pancreatic necrosis, causing obstruction of the gastrointestinal tract. The patient underwent a robotic transgastric drainage and debridement of the WOPN performed with the da Vinci Xi platform. Firstly, an anterior ideal gastrotomy was carried out, guided by intraoperative ultrasound (US)-scan using the TilePro? function. Then, through the gastrotomy, the best location for drainage on the posterior gastric wall was again US-guided identified. The anastomosis between the posterior gastric wall and the walled-off necrosis wall was carried out with the new EndoWrist stapler with vascular cartridge. Debridement and washing of the cavity through the anastomosis were performed. Finally, the anterior gastrotomy was closed and the cholecystectomy was performed. The postoperative course was uneventful and a post-operative computed tomography-scan showed the collapse of the fluid collection. CONCLUSION In selected cases of WOPN the da Vinci Surgical System can be safely used as a valid surgical treatment option.
文摘BACKGROUND The response to chemotherapy treatment of patients with pancreatic ductal adenocarcinoma(PDAC)is difficult to predict and the identification of patients who most likely will benefit from aggressive chemotherapy approaches is crucial.The concept of personalized medicine has emerged in the last years with the objective to tailor the medical treatment to the individual characteristics of each patient,and particularly to the tumor biology of each patient.The need for invivo xenotransplantation models for cancer patients has increased exponentially,and for this reason zebrafish avatars have gained popularity.Preliminary studies were conducted also with PDAC tissue.AIM To develop a simple,not expensive,diffusible zebrafish embryo model as avatar for patients affected by PDAC.METHODS Tumor tissue was taken from the surgical specimen by the histopathologist.After its fragmentation into small pieces,they are stained with CM-Dil.Small pieces of stained tissue were transplanted into the yolk of wt AB zebrafish embryos with a glass capillary needle.Embryos were incubated at 35°C in E3 medium supplemented with 1%Pen/Strep in the presence or absence of drugs for the following days in respect of the treatment plan(Gemcitabine;Gemcitabine and Oxaliplatin;Gemcitabine and nab-Paclitaxel;5-Fluorouracil and Folinic acid and Oxaliplatin and Irinotecan).The response of zebrafish xenografts to the chemotherapy options has been analyzed by monitoring the fluorescent stained area at 2 h post injection(hpi),1 d and 2 d post injection(dpi).In each time point,the mean size of the stained area was measured by ImageJ and it was normalized with respect to the 1 dpi time point mean relative tumor area(RTA).We evaluated the effect of the chemotherapy exposition comparing the mean RTA of each treated subgroup and the control group and evaluating the percentage reduction of the mean RTA by comparing each treated subgroup with the control group.RESULTS Between July 2018 and October 2019,a total of 15 patients with pancreatic cancer were prospectively enrolled.In all cases,it was possible to take a fragment of the tumor from the surgical specimen for the xenotransplantation in the zebrafish embryos.The histological examination confirmed the presence of a PDAC in all cases.In absence of chemotherapy(control group),over time the Dil-stained area showed a statistically significant increase in all cases.A statistically significant reduction of the mean RTA in the treated subgroups for at least one chemotherapy scheme was reported in 6/15(40%)cases.The analysis of the percentage reduction of the RTA in treated subgroups in comparison to the control group revealed the presence of a linear relationship in each subgroup between the percentage reduction of the RTA and the number of cases reporting each percentage threshold considered for the analysis.CONCLUSION Our model seems to be effective for the xenotransplantation of PDAC tissue and evaluation of the effect of each chemotherapy scheme on the xenotransplanted tumor tissue.
文摘BACKGROUND‘Splenosis’is defined as the autotransplantation of splenic tissue following trauma or surgery,usually in the form of intraperitoneal nodules.The proliferation of imaging techniques has resulted in increased unexpected discoveries of splenosis nodules,and achieving a differential diagnosis can be challenging.Nuclear medicine studies have been playing an increasingly important role in this process,but the clinical significance of asymptomatic nodules remains uncertain.CASE SUMMARY We present a case of pelvic splenosis in a 73-year-old man diagnosed 56 years after a splenectomy during a computed tomography(CT)follow-up for B-cell lymphoma,presenting intense contrast enhancement of an 18 mm nodule in the right recto-vesical space.18F-fluorodeoxyglucose demonstrated weak metabolic activity.Since histological diagnosis was deemed necessary,the nodule was easily removed with robotically assisted laparoscopy,together with another 6 mm left a paracolic lesion.The latter was previously undiagnosed but retrospectively visible on the CT scan.CONCLUSION In a patient requiring differential diagnosis of splenosis nodules from lymphomarecurrence, the robotic approach provided a safe en bloc removal with shorthospitalization. The Da Vinci Xi robot was particularly helpful because its opticscan be introduced from all ports, facilitating visualization and lysis of multipleintra-abdominal adhesions.
文摘Worldwide epidemiological reports assert that drinking water is a source for infections and Legionella control represents a critical issue in healthcare settings. Chemical disinfections of water networks are control measures that need to be fine-tuned to obtain satisfactory results in large buildings over prolonged time periods. Aim of study is the evaluation of the effect of anolyte and chlorine dioxide, applied in two different hot water networks of a nursing home to manage Legionella risk. Nursing home has two buildings (A and B), with the same point of aqueduct water entrance. From June 2016, following a shock chlorination, the continuous disinfections with chlorine dioxide and anolyte were applied in hot networks of building A and B, respectively. Hot water was sampled at the central heating system and at two points of use for Legionella research, while chemical tests of manganese (Mn), iron (Fe), zinc (Zn) and trihalomethanes compounds (THM) were implemented to evaluate the disinfection by-products presence. Before chlorination Legionella pneumophila sg1 was recovered with a mean count of 2.4 × 104 CFU/L, while chemical compounds concentrations were within the law limits (Directive 98/83/EC). Then the disinfections Legionella was not recovered in both hot water plants. After the disinfection with chlorine dioxide (from June 2016 to May 2018), a statistically significant increase of iron, zinc and THM concentrations was detected in building A (p = 0.012;p = 0.004;p = 0.008). Both disinfectants appear effective against Legionella spp. growth in water network, but anolyte ensures a lower disinfection by-products release.
文摘AIM:To evaluate the direct and indirect biocompatibility of Filtek Silorane on human gingival fibroblastic cells.METHODS:Sixty-three standardized cylindrical specimens(8 mm diameter and 2 mm thickness)of restorative material were prepared using a light emitting diode-curing unit.The sample were built up in one increment and divided in 2 groups.In the first group,21samples(unpolished samples)were left without a specific polishing procedure;in the second one,42 samples(polished samples)were polished with 4 different grains of discs.Fibroblast cultures,obtained from gingiva of 2 subjects without systemic and oral disease,were used to assess the direct and indirect biocompatibility.Cells cultured for 48 h in normal culture medium were used as a control.RESULTS:The scanning electron microscope observations of fibroblasts cultured on the silorane samples,either polished or unpolished,confirmed the good biocompatibility of the material,favouring the cellular spreading.3-dimethylthiazol-2,5-diphenyltetrazolium bromide tests showed a significant reduction(P<0.01)of gingival fibroblasts viability cultured both in polished samples(90.05%±19.00%)and unpolished samples(78.15%±11.00%)compared with the control.Cells growth in medium conditioned with the samples for 1 wk showed a significant viability reduction(P<0.01)compared to the control.A reduction of cell viability was observed even in the groups containing the material for 3 wk(polished:89.45%±10.00%;unpolished:65.97%±10.00%),even if the cytotoxicity was reduced after this long time exposure.CONCLUSION:Although the poor chromatic availability of this material remains a big limit that restricts its use to posterior sectors,the silorane-based material can be considered an option to perform restorations when aesthetic demands are not the priority,such as the
基金supported Chicago Diahetes Project(CDP)National Institutes of Health(NIH)ROl DK091526,R25 DK105924-01Natural ScienceFoundation of Tianjin,China(13JCYBJC42600)
文摘Gastroparesis(Gp)is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction.Although this condition has been reported in the literature since the mid-1900s,only recently has there been renewed clinical and scientific interest in this disease,which has a potentially great impact on the quality of life.The aim of this review is to explore the pathophysiological,diagnostic and therapeutical aspects of Gp according to the most recent evidence.A comprehensive online search for Gp was carried out using MEDLINE and EMBASE.Gp is the result of neuromuscular abnormalities of the gastric motor function.There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes.As regards diagnostic approach,99-Technetium scintigraphy is currently considered to be the gold standard for Gp.Its limits are a lack of standardization and a mild risk of radiation exposure.The C13 breath testing is a valid and safe alternative method.13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits.The wireless motility capsule is a promising technique,but its use is limited by costs and scarce availability in many countries.Finally,therapeutic strategies are related to the clinical severity of Gp.In mild and moderate Gp,dietary modification and prokinetic agents are generally sufficient.Metoclopramide is the only drug approved by the Food and Drug Administration for Gp.However,other older and new prokinetics and antiemetics can be considered.As a second-line therapy,tricyclic antidepressants and cannabinoids have been proposed.In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed.In drug-unresponsive Gp patients some alternative strategies(endoscopic,electric stimulation or surgery)are available.
文摘Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus(T1DM) and T2 DM. T2 DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1 DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2 DM and chronic hepatitis C(CHC) infection. The processes through which CHC is associated with T2 DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immunemediated mechanisms. Few data have been reported on the association of CHC and T1 DM and reports on the potential association between T1 DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoim-munity and in certain cases lead to the development of T1 DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with nondiabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effec-tive programmes for the surveillance and treatment of diabetic CHC patients.
文摘Gastroesophageal reflux disease(GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry(HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h p H-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and p H monitoring can detect acid and non-acid reflux events. Endo FLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal p H-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.
文摘Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy production.They are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.
