Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults:A retrospective study

BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycininduced focal segmental glomerulosclerosis

BACKGROUND Bone marrow-derived mesenchymal stem cells(MSCs)show podocyte-protective effects in chronic kidney disease.Calycosin(CA),a phytoestrogen,is isolated from Astragalus membranaceus with a kidney-tonifying effect.CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion.However,the protective effect and underlying mechanism of CA-pretreated MSCs(MSCsCA)on podocytes in adriamycin(ADR)-induced focal segmental glomerulosclerosis(FSGS)mice remain unclear.AIM To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved.METHODS ADR was used to induce FSGS in mice,and MSCs,CA,or MSCsCA were administered to mice.Their protective effect and possible mechanism of action on podocytes were observed by Western blot,immunohistochemistry,immunofluorescence,and real-time polymerase chain reaction.In vitro,ADR was used to stimulate mouse podocytes(MPC5)to induce injury,and the supernatants from MSC-,CA-,or MSCsCA-treated cells were collected to observe their protective effects on podocytes.Subsequently,the apoptosis of podocytes was detected in vivo and in vitro by Western blot,TUNEL assay,and immunofluorescence.Overexpression of Smad3,which is involved in apoptosis,was then induced to evaluate whether the MSCsCA-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells.RESULTS CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells.Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells,which was reversed by MSCCA treatment more significantly than by MSCs or CA alone.When Smad3 was overexpressed in MPC5 cells,MSCsCA could not fulfill their potential to inhibit podocyte apoptosis.CONCLUSION MSCsCA enhance the protection of MSCs against ADR-induced podocyte apoptosis.The underlying mechanism may be related to MSCsCA-targeted inhibition of p-Smad3 in podocytes.

Focal Segmantal Glomerulosclerosis: Epidemiological, Clinico-Biological, Pathological, Etiological, Therapeutic and Evolutionary Profiles in Dakar

Introduction: Focal Segmental Glomerulosclerosis (FSGS) corresponds to a clinicopathological syndrome, manifested by generally abundant proteinuria associated with hyaline deposits on part of certain glomeruli and sparing other glomeruli, with effacement of the pedicels. The general objective was to determine the prevalence of FSGS, and to give its profiles;epidemiological, clinical, biological, pathological, etiological, therapeutic and evolutionary of FSGS. Materials and Methods: This is a retrospective analytical study over a period of six years extending from January 1, 2010 to December 31, 2015 patients aged 16 or over who were hospitalized or received consultations during the study period for primary or secondary segmental and focal hyalinosis. Patients whose records were incomplete or unusable were not included in the study. Results: We have 16.54% with 158 cases of FSGS out of 6945 patients received and/or hospitalized. Of the 955 kidney biopsies distributed, the incidences of HSF were;10.15%;14.04%;15%;17.64%;20.11%;19.58% respectively in 2010;2011;2012;2013;2014 and 2015, i.e. an annual increase of around 1.25%. Renal-type edemas were found in 93.3%, the first reason for hospitalization. And ninety-six people had impaired kidney function, or 61%. The average of 24-hour proteinuria was 6.4 ± 3.69 g/24 hours. The extremes were 0.37 and 18.50 g/24h. Patients had nephrotic proteinuria in 84.86%. Non-specific FSGS or NOS (Not Other Specificities) was found in 62 cases or 39.24%, collapsing FSGS in 48 cases or 30.40%. FSGS with found causes was associated with fibrosis in 5/35 cases. Collapsing FSGSs followed by NOS FSGSs were the most corticosteroid-resistant. The evolution of the FSGS reveals that every 8 months the proteinuria decreases by half. Conclusion: Segmental and focal hyalinosis requires histological confirmation and the epidemiological, clinico-biological, etiological, therapeutic and evolutionary profiles depend on the histological (pathological) type. Other works on the risk factors for occurrence and the contribution of electron microscopy in the primary and secondary diagnosis of segmental and focal hyalinosis are desired.

Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

Focal segmental glomerulosclerosis(FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts(30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo " type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.

Rituximab or plasmapheresis for prevention of recurrent focal segmental glomerulosclerosis after kidney transplantation:A systematic review and meta-analysis

BACKGROUND Focal segmental glomerulosclerosis(FSGS)is one of the most common glomerular diseases leading to renal failure.FSGS has a high risk of recurrence after kidney transplantation.Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results.AIM To assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis,and plasmapheresis alone compared to the standard treatment group without preventive therapy.METHODS This meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE,EMBASE,and Cochrane databases,from inception through March 2021;search terms included‘FSGS,’’steroid-resistant nephrotic syndrome’,‘rituximab,’and‘plasmapheresis,’.We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis,or plasmapheresis alone.Inclusion criteria were:Original,published,randomized controlled trials or cohort studies(either prospective or retrospective),case-control,or cross-sectional studies;inclusion of odds ratio,relative risk,and standardized incidence ratio with 95%confidence intervals(CI),or sufficient raw data to calculate these ratios;and subjects without interventions(controls)being used as comparators in cohort and cross-sectional studies.Effect estimates from individual studies were extracted and combined using a random effects model.RESULTS Eleven studies,with a total of 399 kidney transplant recipients with FSGS,evaluated the use of rituximab with or without plasmapheresis;thirteen studies,with a total of 571 kidney transplant recipients with FSGS,evaluated plasmapheresis alone.Post-transplant FSGS recurred relatively early.There was no significant difference in recurrence between the group that received rituximab(with or without plasmapheresis)and the standard treatment group,with a pooled risk ratio of 0.82(95%CI:0.47-1.45,I2=65%).Similarly,plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis;the pooled risk ratio was 0.85(95%CI:0.60-1.21,I2=23%).Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk.We also reviewed and analyzed posttransplant outcomes including timing of recurrence and graft survival.CONCLUSION Overall,the use of rituximab with or without plasmapheresis,or plasmapheresis alone,is not associated with a lower risk of FSGS recurrence after kidney transplantation.Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence.

Case of human immunodeficiency virus infection presenting as a tip variant of focal segmental glomerulosclerosis: A case report and review of the literature

The incidence of the collapsing variant of focal segmental glomerulosclerosis(FSGS) as a human immunodeficiency virus(HIV)-associated nephropathy has reduced since the introduction of antiretroviral therapy(ART). However, the incidence of other variants of FSGS, except for the collapsing variant, is increasing, and its therapeutic strategies remain uncertain. A 60-year-old HIV infected man in remission with ART was admitted for progressive renal insufficiency and nephrotic-ranged proteinuria. Renal biopsy revealed a tip variant of FSGS and his clinical manifestations resolved with corticosteroid therapy. HIV infected patients might develop non-collapsing FSGS, including tip variant of FSGS and corticosteroid therapy might be effective for them. A renal biopsy might be essential to determine the renal histology and to decide on corticosteroid therapy.

Transition from minimal change disease to focal segmental glomerulosclerosis related to occupational exposure:A case report

BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a patient transitioning from MCD to FSGS,review the literature,and explore the relationship between the two diseases.CASE SUMMARY A 42-year-old male welder,presenting with lower extremity edema and elevated serum creatinine,was diagnosed with NS and end-stage kidney disease(ESKD)based on laboratory test results.The patient had undergone a kidney biopsy for NS 20 years previously,which indicated MCD,and a second recent kidney biopsy suggested FSGS.The patient was an electric welder with excessive levels of cadmium and lead in his blood.Consequently,we suspect that his aggravated pathology and occurrence of ESKD were related to metal nephrotoxicity.The patient eventually received kidney replacement therapy and quit his job which involved long-term exposure to metals.During the 1-year follow-up period,the patient was negative for metal elements in the blood and urine and recovered partial kidney function.CONCLUSION MCD and FSGS may be different stages of the same disease.The transition from MCD to FSGS in this case indicates disease progression,which may be related to excessive metal contaminants caused by the patient’s occupation.

Non-glomerular Tip Lesion Focal Segmental Glomerulosclerosis as a Negative Predictor in Idiopathic Membranous Nephropathy

Objective To assess the significance of focal segmental glomerulosclerosis(FSGS)variants on clinicopathological characteristics and short-term outcomes in idiopathic membranous nephropathy(IMN)patients.Methods The clinicopathological data of 146 IMN patients diagnosed between December 2016 and March 2019 in our center were collected and analyzed.These patients were divided into the pure IMN group,IMN with glomerular tip lesion(GTL)group,and IMN with non-GTL FSGS group.Results The IMN with non-GTL FSGS and IMN with GTL groups both had higher proportions of patients with hypertension,lower serum albumin,and severe proteinuria,while the IMN with non-GTL FSGS group additionally showed higher blood pressure and serum cholesterol,and lower serum IgG than the IMN group(all P<0.05).As for pathology,the IMN with non-GTL FSGS group had higher proportions of patients with acute tubular injury and moderate to severe chronic injuries than the IMN group(all P<0.05).In the IMN,IMN with GTL,and IMN with non-GTL FSGS groups,the overall one-year remission rates were 81.6%,76%,and 58.8%,respectively.Furthermore,the IMN with non-GTL FSGS group showed the lowest cumulative incidence to reach remission within one year.Multivariate Cox logistic analysis demonstrated that higher level of serum anti-M-type phospholipase A2 receptor antibody and the existence of non-GTL FSGS lesion were independent predictors for no remission in IMN patients.Conclusion The non-GTL FSGS lesion was a novel negative predictor in IMN and should be taken into account in the management of IMN.

Collapsing focal segmental glomerulosclerosis: Current concepts

Collapsing focal segmental glomerulosclerosis(cF SGS), also known as collapsing glomerulopathy is currently classified under the rubric of FSGS. However, its defining morphological features are in stark contrast to those observed in most other variants of FSGS. During the early stage of the disease, the lesion is characterized pathologically by an implosive segmental and/or global collapse of the glomerular capillary tufts, marked hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial disease. With advancement of the disease, segmental and/or global glomerulosclerosis is also observed in association with the collapsing lesions. The etiology of this enigmatic disorder is still elusive, but a growing list of diseases/conditions is being reported in association with this morphological pattern of renal parenchymal injury. The pathogenesis of cF SGS involves discreet epithelial cell injury leading to cell cycle dysregulation and a proliferative cellular phenotype. From the clinical perspective, cF SGS is notorious for its propensity to affect black people, a high incidence and severity of nephrotic syndrome, marked resistance to empirical therapy, and rapid progression to end-stage renal disease. The lesion has also been reported in transplanted kidneys either as recurrent or de novo disease, frequently leading to graft loss. Mostcases have been reported in western countries, but the lesion is also being increasingly recognized in the tropical regions. The recent increase in reporting of cF SGS partly reflects a true increase in the incidence and partly a detection bias. There is no specific treatment for the disorder at present. Newer insights into the pathogenesis may lead to the development of targeted and specific therapy in near future. There is an urgent need to increase awareness of the lesion among pathologists and nephrologists, especially those from developing countries, to ensure accurate diagnosis and appropriate managment. With the accumulation of more and more data, it is hoped that the prevailing confusion about the nosological identity of the lesion will also be resolved in a more logical way.

Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor

Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.

Design and fabrication of compound varifocal lens driven by polydimethylsiloxane film elastic deformation

A compound varifocal lens based on electromagnetic drive technology is designed and fabricated, where the polydimethylsiloxane(PDMS) film acts as a driving component, while the PDMS biconvex lens and the plane-concave lens form a coaxial compound lens system. The plane-concave lens equipped with driving coils is installed directly above the PDMS lens surrounded by the annular magnet. When different currents are applied, the annular magnet moves up and down, driving the PDMS film to undergo elastic deformation, and then resulting in longitudinal movement of the PDMS lens. The position change of the PDMS lens changes the focal length of the compound lens system. To verify the feasibility and practicability of this design, a prototype of our compound lens system is fabricated in experiment. Our proposed compound lens shows that its zoom ability reaches 9.28 mm when the current ranges from -0.20 A to 0.21 A.

Constraint on the focal mechanism of the 2011 Tohoku earthquake from the radial modes

Different from other normal modes of the Earth’s free oscillation that depend on all the six components(M_(rr),M_(tt),M_(pp),M_(rt),M_(rp),and M_(tp))of the centroid moment tensor,the amplitudes of the radial modes depend on the M_(rr)component(e.g.,scalar moment(M_(0)),dip(δ),and slip(λ))and hypocenter depth of the focal mechanism,and hence can be easily used to constrain these parameters of the focal mechanism.In this study,we use the superconducting gravimeter(SG)records after the 2011 Tohoku earthquake to analyze the radial modes_(0)S_(0)and_(1)S_(0).Based on the solutions of the focal mechanism provided by the GCMT and USGS,we can obtain the theoretical amplitudes of these two radial modes.Comparing the theoretical amplitudes with the observation amplitudes,it is found that there are obvious differences between the former and the latter,which means that the GCMT and USGS focal mechanisms cannot well represent the real focal mechanism of the 2011 event.Taking the GCMT solution as a reference and changing the depth and the three parameters of the M_(rr)moment,the scalar moment(M_(0))and the dip(δ)have significant influences,but the effects of the slip(λ)and the depth are minor.After comparisons,we provide a new constraint(M_(0)=5.8±0.09×10^(22)N·m,δ=10.1±0.08°,λ=88°,and depth=20 km)for the focal mechanism of the 2011 event.In addition,we further determine the center frequency(1.631567±2.6e^(-6)mHz)and quality factor(2046.4±50.1)of the_(1)S_(0)mode.

Focal incidental colorectal fluorodeoxyglucose uptake:Should it be spotlighted?

Fluorine-18 fluorodeoxyglucose(F-18 FDG)positron emission tomography/computed tomography(PET/CT)has emerged as a cornerstone in cancer evaluation imaging,with a well-established history spanning several years.This imaging modality,encompassing the examination of the body from the base of the skull to the upper thighs,comprehensively covers the chest and abdominopelvic regions in a singular scan,allowing for a holistic assessment of nearly the entire body,including areas of marginal interest.The inherent advantage of this expansive scan range lies in its potential to unveil unexpected incidental abnormal hypermetabolic areas.The identification of incidental focal FDG uptake within colorectal regions during PET/CT scans is not an uncommon occurrence,albeit fraught with challenges associated with non-specific FDG uptake.The presence of benign colorectal lesions or physiological uptake poses a particular obstacle,as these may manifest with FDG uptake levels that mimic malignancy.Consequently,physicians are confronted with a diagnostic dilemma when encountering abnormal FDG uptake in unexpected colorectal areas.Existing studies have presented divergent results concerning these uptakes.Standardized uptake value and its derivatives have served as pivotal metrics in quantifying FDG uptake in PET images.In this article,we aim to succinctly explore the distinctive characteristics of FDG,delve into imaging findings,and elucidate the clinical significance of incidental focal colorectal uptake.This discussion aims to contribute valuable insights into the nuanced interpretation of such findings,fostering a comprehensive understanding.

Unexpected focal fluorodeoxyglucose uptake in main organs;pass through or pass by?

Since the inception of fluorine-18 fluorodeoxyglucose(F-18 FDG),positron emission tomography/computed tomography(PET/CT)utilizing F-18 FDG has become widely accepted as a valuable imaging modality in the field of oncology,with global prevalence in clinical practice.Given that a single Torso PET/CT scan encompasses the anatomical region from the skull base to the upper thigh,the detection of incidental abnormal focal hypermetabolism in areas of limited clinical interest is both feasible and not uncommon.Numerous investigations have been undertaken to delineate the distinctive features of these findings,yet the outcomes have proven inconclusive.The incongruent results of these studies present a challenge for physicians,leaving them uncertain about the appropriate course of action.This article provides a succinct overview of the characteristics of fluorodeoxyglucose,followed by a comprehensive discussion of the imaging findings and clinical significance associated with incidental focal abnormal F-18 FDG activity in several representative organs.In conclusion,while the prevalence of unrecognized malignancy varies across organs,malignancies account for a substantial proportion,ranging from approximately one-third to over half,of incidental focal uptake.In light of these rates,physicians are urged to exercise vigilance in not disregarding unexpected uptake,facilitating more assured clinical decisions,and advocating for further active evaluation.

Carcinoembryonic antigen in the diagnosis,treatment,and follow-up of focal liver lesions

In this editorial review,we comment on the article published in the recent issue of the World Journal of Gastrointestinal Surgery.Carcinoembryonic antigen(CEA)is a fetal glycoprotein and can be secreted in very small amounts from healthy adults after birth.CEA is widely used not only for diagnostic tumor markers but also importantly for the management of some gastrointestinal tumors.The most common clinical use is surveillance for the monitoring of colorectal carcinoma.However,CEA can become elevated in several malign or benign characterized pathologies.Serum CEA level may vary depending on the location of the lesion,whether it metastasizes or not,and its histopathological characteristics.It has been determined that cases with high preoperative CEA have a more aggressive course and the risk of metastasis to the lymph tissue and liver increases.In this editorial review,we focused on evaluating the role of CEA in clinical practice with a holistic approach,including the diagnostic and prognostic significance of CEA in patients with focal liver lesions,the role of CEA in follow-up after definitive surgery,and also hepatic resection for metastasis,and the management of all patients with raised CEA.

Towards fast focal mechanism inversion of shallow crustal earthquakes in the Chinese mainland

We have developed an automatic regional focal mechanism inversion system based on the Earthquake Rapid Report(ERR) system and the real-time three-component seismic waveform stream of 1 000 broadband seismic stations provided by the China Earthquake Networks Center(CENC). The system can rapidly provide a double couple solution and centroid depth within 5–15 min after receiving earthquake information from the ERR system.The data processing is triggered by earthquake information obtained from the ERR system. The system is capable of determining the focal mechanism of all shallow-depth earthquakes in the Chinese mainland with a magnitude of 5.5–6.5. It utilizes waveform data recorded by seismic stations located within 500 km from the epicenter,enabling the reporting of a focal mechanism solution within 5–15 min of an earthquake occurrence. Additionally,the system can assign a corresponding grade(A B C) to the focal mechanism solution. We processed a total of 301earthquakes that occurred from 2021 to June 2022, and after the quality control, 166 of them were selected.These selected solutions were manually checked, and 160 of them were compiled in a focal mechanism catalog.This catalog can be conveniently downloaded online via the Internet. The automatic focal mechanism solution of earthquakes in eastern China exhibits a good agreement with that provided by the Global Centroid Moment Tensor(GCMT), when available. The average Kagan angle between this catalog and GCMT is 22°, and the average difference in MWis 0.17. Furthermore, compared with GCMT, the minimum magnitude of our catalog has been reduced from approximately 5.0 to 4.0. The correlation between the centroid depth and crustal thickness in the Chinese mainland confirms the distribution of the centroid depth.

Imaging features and management of focal liver lesions

Notably,the number of incidentally detected focal liver lesions(FLLs)has increa-sed dramatically in recent years due to the increased use of radiological imaging.The diagnosis of FLLs can be made through a well-documented medical history,physical examination,laboratory tests,and appropriate imaging methods.Although benign FLLs are more common than malignant ones in adults,even in patients with primary malignancy,accurate diagnosis of incidental FLLs is of utmost clinical significance.In clinical practice,FLLs are frequently evaluated non-invasively using ultrasound(US),computed tomography(CT),and magnetic resonance imaging(MRI).Although US is a cost-effective and widely used imaging method,its diagnostic specificity and sensitivity for FLL characterization are limited.FLLs are primarily characterized by obtaining enhancement patterns through dynamic contrast-enhanced CT and MRI.MRI is a problem-solving method with high specificity and sensitivity,commonly used for the evaluation of FLLs that cannot be characterized by US or CT.Recent technical advancements in MRI,along with the use of hepatobiliary-specific MRI contrast agents,have significantly improved the success of FLL characterization and reduced unnece-ssary biopsies.The American College of Radiology(ACR)appropriateness criteria are evidence-based recommendations intended to assist clinicians in selecting the optimal imaging or treatment option for their patients.ACR Appropriateness Criteria Liver Lesion-Initial Characterization guideline provides recommend-ations for the imaging methods that should be used for the characterization of incidentally detected FLLs in various clinical scenarios.The American College of Gastroenterology(ACG)Clinical Guideline offers evidence-based recommend-ations for both the diagnosis and management of FLL.American Association for the Study of Liver Diseases(AASLD)Practice Guidance provides an approach to the diagnosis and management of patients with hepatocellular carcinoma.In this article,FLLs are reviewed with a comprehensive analysis of ACR Appropri-ateness Criteria,ACG Clinical Guideline,AASLD Practice Guidance,and current medical literature from peer-reviewed journals.The article includes a discussion of imaging methods used for the assessment of FLL,current recommended imaging techniques,innovations in liver imaging,contrast agents,imaging features of common nonmetastatic benign and malignant FLL,as well as current management recommendations.

Endoscopic ultrasound-guided tissue acquisition for the diagnosis of focal liver lesion

In patients with liver tumors,the histopathology examination can assist in diagnosis,staging,prognosis,and therapeutic management strategy.Endoscopic ultrasound(EUS)-guided tissue acquisition using fine needle aspiration(FNA)or more newly fine needle biopsy(FNB)is a well-developed technique in order to evaluate and differentiate the liver masses.The goal of the EUS-FNA or EUS-FNB is to provide an accurate sample for a histopathology examination.Therefore,malignant tumors such as hepatocarcinoma,cholangiocarcinoma and liver metastasis or benign tumors such as liver adenoma,focal hyperplastic nodular tumors and cystic lesions can be accurately diagnosed using EUS-guided tissue acquisition.EUS-FNB using 19 or 22 Ga needle provide longer samples and a higher diagnostic accuracy in patients with liver masses when compared with EUS-FNA.Few data are available on the diagnostic accuracy of EUS-FNB when compared with percutaneously,ultrasound,computer tomography or transjugulary-guided liver biopsies.This review will discuss the EUS-guided tissue acquisition options in patients with liver tumors and its efficacy and safety in providing accurate samples.The results of the last studies comparing EUS-guided liver biopsy with other conventional techniques are presented.The EUS-guided tissue acquisition using FNB can be a suitable technique in suspected liver lesions in order to provide an accurate histopathology diagnosis,especially for those who require endoscopy.

正常小鼠血清通过抑制focal adhesion信号通路减轻小鼠放射性肺炎

目的探讨正常小鼠血清(NMS)对放射性肺炎的治疗作用及可能机制。方法建立胸腔照射诱导的放射性肺炎模型,将小鼠分为对照组、静脉注射血清组、照射组和照射后静脉注射血清组。注射血清组小鼠在照射后立即静脉注射正常小鼠血清100μL,对照组小鼠注射100μL生理盐水,隔天注射1次,共注射8次。照射后15 d取材,HE染色检测肺组织形态学变化,ELISA检测小鼠肺组织和血清中炎症因子肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)、白细胞介素-1α(IL-1α)、白细胞介素-6(IL-6)水平;流式细胞术检测肺组织内淋巴细胞比例变化。外泌体miRNA高通量测序探索处理后小鼠的信号通路变化,qRT-PCR检测免疫相关基因的表达水平,使用Western blotting检测黏着斑通路talin-1、tensin 2、FAK、vinculin、α-actinin和paxillin蛋白的表达。结果与照射组相比,照射后注射血清组小鼠肺脏器系数、血清及肺组织上清液中炎症因子TNF-α、TGF-β、IL-1α、IL-6水平显著降低(P<0.05),CD45^(+)、CD4^(+)、T_(reg)淋巴细胞在小鼠肺组织中的浸润程度显著下降(P<0.05);肺中Egfr和Pik3cd的mRNA和蛋白表达水平显著下调,talin-1、tensin 2、FAK、vinculin、α-actinin和paxillin蛋白的表达水平也显著降低(P<0.05)。结论正常小鼠血清通过抑制focal adhesion信号通路关键蛋白的表达减轻电离辐射诱发的小鼠放射性肺炎。

Focal ablation therapy presents promising results for selectively localized prostate cancer patients

Due to its lower risk of consequences when compared to a radical approach, focal treatment is a viable and minimally invasive option for treating specific localized prostate cancer. Although several recent good nonrandomized trials have suggested that focused therapy may be an alternative choice for some patients, additional high-quality evidence is needed before it can be made widely available as a conventional treatment. As a result, we have summarized the most recent findings from the 38th Annual European Association of Urology Congress, one of the most renowned annual conferences in the area of urology, regarding focal ablation therapy for patients with localized prostate cancer. Additionally, we also provided clinical trials in progress for researchers to better understand the current research status of this field.