BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically e...BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.展开更多
BACKGROUND Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract(ITLPDGI),a primary tumor forming in the gastrointestinal(GI)tract,represents a rarely diagnosed clonal T-cell disease with a protra...BACKGROUND Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract(ITLPDGI),a primary tumor forming in the gastrointestinal(GI)tract,represents a rarely diagnosed clonal T-cell disease with a protracted clinical course.CASE SUMMARY This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation.Postsurgical histopathological analysis,combined with hematoxylineosin staining,immunohistochemistry and TCRβ/γ clonal gene rearrangement test,confirmed the diagnosis of CD8+ITLPD-GI.CONCLUSION Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize.So far,indolent CD8+ITLPD-GI has not been comprehensively examined.The current mini-review focused on evaluating indolent CD8+ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis,detection of genetic and epigenetic alterations,and therapeutic target identification.展开更多
Backgrounds and Purpose—In indolent non-Hodgkin lymphoma, histological transformation is a dramatic event which reduces the prognosis significantly. SUVmax values from FDG-PET/CT help differentiate between aggressive...Backgrounds and Purpose—In indolent non-Hodgkin lymphoma, histological transformation is a dramatic event which reduces the prognosis significantly. SUVmax values from FDG-PET/CT help differentiate between aggressive and indolent lymphomas, and transformed indolent lymphomas also show an increased FDG uptake. Possibly FDG uptake increases early in the clinical course and could predict histological transformation. Our objective was to predict histological transformation in indolent lymphomas from initial staging FDG-PET/CT. Patients and Methods—A retrospective study was performed. Patients with biopsy-proven indolent lymphoma who had had initial staging FDG-PET/CT were included. Qualitative (foci compared with FDG uptake liver) and semiquantitative (SUVmax-value per focus) analyses were performed of all abnormal foci. Patient characteristics and outcome were evaluated. Results—We included 88 patients, 5 of whom developed a histological transformation. Semiquantitative analysis showed a relation between maximum standardized uptake value and histological transformation (odds ratio 1.25, 95% CI 1.024 - 1.513). Qualitative analysis showed a negative predictive relation of FDG uptake less than or equal to liver in the occurrence of histological transformation. Transformation-free survival was 100% over 30 months in those with FDG uptake lower than or equal to liver. More FDG uptake than liver showed transformation-free survival of 88% over 30 months. Conclusion—Qualitative analysis of staging FDG-PET/CT in indolent lymphomas could be useful to rule out transformation in the next 30 months. In our study, semiquantitative analysis was statistically significantly associated with histological transformation and maximum standardized uptake value. However, because of the small number of patients, cautious interpretation of the results is warranted. More studies are needed to investigate the role of staging PET/CT in patient with indolent non-Hodkin lymphoma in the prediction of transformation.展开更多
The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk st...The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded （FFPE） tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.展开更多
Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an uncommon subtype of EBV associated lymphoma usually characterized by aggressive clinical course. We report an atypical sinonasal ENKL case with long-lasting indo...Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an uncommon subtype of EBV associated lymphoma usually characterized by aggressive clinical course. We report an atypical sinonasal ENKL case with long-lasting indolent behaviour, developed in the setting of a polymorphic EBV-associated lymphoproliferative disorder (LPD). A 52-year-old woman had suffered from chronic sinusitis and nasal obstruction since 2000, moderately worsened during the last years (marked enlargement of the sino-nasal mucosa at MRI in 2011) with elevated anti-VCA IgG and IgM titers. Three subsequent biopsies revealed slightly increasing morphophenotypic atypia, ranging from a polymorphic B- and T-cell EBV positive proliferation (diagnosed in 2011, but not fulfilling CAEBV diagnostic criteria) to an overt monomorphic mildly atypical T LPD without necrosis and angiocentricty diagnosed as ENKL in 2013 upon immunophenotype and TCR-γ gene clonal rearrangement. Clinically indolent ENKL with low-grade morphology is extremely rare and diagnostically challenging;while the few reports in the literature describe long-survival in ENKL treated patients comparing histologically neoplastic lesions at onset and recurrences, no reports are published on the slow progression from a polymorphic EBV-related T/NK proliferation to a histologically overt clinically indolent ENKL in an untreated patient who only received occasional steroid administration.展开更多
Background:The natural disease course for patients with ulcerative colitis(UC)is heterogeneous and few data are available on the indolent course of UC and its related factors.We aimed to develop and validate a nomogra...Background:The natural disease course for patients with ulcerative colitis(UC)is heterogeneous and few data are available on the indolent course of UC and its related factors.We aimed to develop and validate a nomogramto predict indolent course in patients with UC.Methods:Data of patients diagnosed with UC in the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between April 2007 and February 2021 were retrospectively analysed.Indolent course was defined as a disease course without need for strict interventions(steroids,immunomodulators,biological agents,hospitalization,or surgery therapy)during the follow-up period.The whole cohort was randomly divided into training set and validation set.The nomogram was constructed in the training set based on the results of univariate and multivariate Cox regression analyses.The performance of the nomogram was assessed by the concordance index(C-index),area under the receiver-operating characteristic curve(AUC),and calibration plots.In addition,we internally validated the nomogramvia the bootstrap method and the validation set.Results:Of 969 treatment-naive patients with UC,771(79.6%)had an indolent course after diagnosis.Of these,313 patients were included in the development and validation of the nomogram.The nomogram incorporating age,disease activity,C-reactive protein,and platelet count showed good calibration and discrimination.The C-index was 0.759(0.741 in bootstrap validation)and the AUC at 2,4,and 6 years was 0.767,0.782,and 0.775,respectively.The nomogramperformed well when applied to the validation set.Conclusion:A majority of patients with UC had an indolent course after diagnosis.The nomogram developed in this study might be useful in therapeutic decision-making and follow-up management for patients with UC.展开更多
Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,whic...Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.展开更多
Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]iso...Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.展开更多
multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from e...multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.展开更多
Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the con...Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.展开更多
Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and ef...Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and efficient synthetic approach was reported for access of a series of C2 or C3-(cycloheptatrienyl)-substituted indoles.A wide range of functional groups can be well tolerated in this transformation,especially including hydroxyl,halo,carboxylic acid and its derivative groups.Based on these results,a rational mechanism via electrophilic substitution of indoles with tropylium tetrafluoroborate is proposed.展开更多
As a natural alkaloid found extensively in cereal crops, gramine not only plays a crucial role in protecting barley and other grasses from various pests, but also reduces palatability for ruminants. Scientists are try...As a natural alkaloid found extensively in cereal crops, gramine not only plays a crucial role in protecting barley and other grasses from various pests, but also reduces palatability for ruminants. Scientists are trying to figure out how gramine gets into cereal plants: is it inherently present or transformed through a special process? The latest study published in Science by Sara Leite Dias and co-authors, provides a detailed explanation. The starting point of the transformation is identified, and the transformation process is confirmed through rigorous experiments.展开更多
Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells spe...Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells specific to tetracycline in Vibrio splendidus were characterized.The tnaA Vs gene was first cloned and conditionally expressed in Escherichia coli Rosetta(DE3).To investigate the regulatory effect of TnaA Vs,the tnaA deletion strain AJ01/ΔtnaA was constructed by in-frame deletion.The undetected extracellular indole in the AJ01/ΔtnaA indicated that TnaA was the solo enzyme to produce indole in V.splendidus.The drop plate method showed that AJ01/ΔtnaA was more tolerant to the higher concentration of tetracycline than that of AJ01,being 340-fold higher in the proportion of survived cells when cell density OD 600≈0.65.Moreover,the synergistic effects of indole and tetracycline on killing of V.splendidus were determined.Results show that addition of 2-mmol/L indole increased the susceptibility of both AJ01 and AJ01/ΔtnaA to 10×minimum inhibitory concentration tetracycline.To explore the genes and pathways regulated by TnaA Vs,the transcriptomic analysis between AJ01 and AJ01/ΔtnaA was performed.Result shows that TCA cycle,arginine biosynthesis,quorum sensing and microbial metabolism in diverse environments were downregulated,while the ribosome pathways,the protein metabolic process,peptide biosynthetic and metabolic process were upregulated in the AJ01/ΔtnaA.This study shows that indole could enhance the bactericidal effect of tetracycline on V.splendidus by decreased ribosome level probably but increased ATP level.展开更多
Black spot,a fungal disease caused by Alternaria brassicae infection,inflicts severe damage on Chinese cabbage.Through comparative transcriptomic analysis,this study investigated the molecular mechanisms underlying Ch...Black spot,a fungal disease caused by Alternaria brassicae infection,inflicts severe damage on Chinese cabbage.Through comparative transcriptomic analysis,this study investigated the molecular mechanisms underlying Chinese cabbage’s defense responses to A.brassicae infection.Notably,we found that the expression of BrERF109 was induced by A.brassicae infection.Silencing of BrERF109 by an optimized virus-induced gene silencing(VIGS)assay in Chinese cabbage diminished disease resistance,while BrERF109-overexpression in Arabidopsis enhanced it.Additionally,BrERF109 silencing in Chinese cabbage suppressed indolic glucosinolates gene expression,substantially reducing indolic glucosinolates levels,whereas BrERF109-overexpression in Arabidopsis promoted their accumulation.BrERF109 directly interacts with the BrIGMT4 promoter,thereby facilitating indolic glucosinolates accumulation and enhancing defense against A.brassicae.This study elucidates the BrERF109-BrIGMT4 regulatory module in Chinese cabbage’s defense against A.brassicae infection,while providing valuable data for further investigation of plant-A.brassicae interactions.展开更多
The first total synthesis of(+)-taberdicatine B and(+)-tabernabovine B has been accomplished in 10steps with 26.9% overall yield and 15 steps with 7.3% overall yield,respectively.The prominent features of this efficie...The first total synthesis of(+)-taberdicatine B and(+)-tabernabovine B has been accomplished in 10steps with 26.9% overall yield and 15 steps with 7.3% overall yield,respectively.The prominent features of this efficient synthetic strategy include the following:(1)(+)-Taberdicatine B and(+)-tabernabovine B were accessed from common advanced intermediates by varying the substituents;(2) A one-pot asymmetric bromocyclization/hydrolysis was explored to assemble HPI skeleton;(3) Dieckmann condensation to form β-keto ester for the assembly of seven-membered ring;(4) An ester reduction/amide semireduction/cyclization sequence was applied to form the cage-like framework.展开更多
AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics re...AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.展开更多
AIM:To examine whether addition of 3T multiparametric magnetic resonance imaging(mp MRI)to an active surveillance protocol could detect aggressive or progressive prostate cancer.METHODS:Twenty-three patients with low ...AIM:To examine whether addition of 3T multiparametric magnetic resonance imaging(mp MRI)to an active surveillance protocol could detect aggressive or progressive prostate cancer.METHODS:Twenty-three patients with low risk disease were enrolled on this active surveillance study,all of which had Gleason score 6 or less disease.All patients had clinical assessments,including digital rectal examination and prostate specific antigen(PSA)testing,every 6 mo with annual 3T mp MRI scans with gadolinium contrast and minimum sextant prostate biopsies.The MRI images were anonymized of patient identifiers and clinical information and each scan underwentradiological review without the other results known.Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mp MRI to identify prostate cancer and progressive disease were calculated.RESULTS:During follow-up(median 24.8 mo)11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment.Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years.All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mp MRI scans at baseline(43.5% sensitivity).Aggressive disease prediction from baseline mpM RI scans had satisfactory specificity(81.8%)but low sensitivity(58.3%).Twentytwo patients had serial mp MRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy(30% specificity and 100% sensitivity).CONCLUSION:Addition of mp MRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.展开更多
BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL)is extremely low,and the clinical symptoms are atypical,which makes it difficult to distinguish this disorder from Crohn's disease(CD),T lymphocyte p...BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL)is extremely low,and the clinical symptoms are atypical,which makes it difficult to distinguish this disorder from Crohn's disease(CD),T lymphocyte proliferative disease,and other immune disorders.The misdiagnosis rate is high,and the patient's prognosis is poor.CASE SUMMARY In this case,the patient had repeated high fever,colonoscopy revealed multiple ulcers,and the initial diagnosis was CD.The patient’s condition did not improve after treatment with hormones and infliximab,and she eventually died.Positron emission tomographic-computed tomographic and B-ultrasound were performed in our hospital and showed that multiple lymph nodes were enlarged.Immunohistochemi-stry showed that CD3 and Epstein-Barr virus encoded RNA expression was positive.Colonoscopy,tissue biopsy,and histopathology showed intestinal focal mucosal infiltration of heterotypic lymphocytes with an abnormal immune phenotype.On the basis of the patient’s medical history,auxiliary examination,and pathological findings,digestive physicians and pathologists gave the diagnosis of NKTCL.CONCLUSION Clinicians need to improve their comprehensive knowledge of NKTCL,and combination of clinical symptoms,histological characteristics,as well as colonoscopy biopsies should be considered to improve the diagnosis and thereby reduce misdiagnosis.展开更多
A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer...A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer and human hepatic cancer cell lines, and compound 6, which is slightly different from 5 in its structure, showed good anticancer activity over human colorectal cancer cell line.展开更多
基金Supported by The National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-132.
文摘BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.
文摘BACKGROUND Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract(ITLPDGI),a primary tumor forming in the gastrointestinal(GI)tract,represents a rarely diagnosed clonal T-cell disease with a protracted clinical course.CASE SUMMARY This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation.Postsurgical histopathological analysis,combined with hematoxylineosin staining,immunohistochemistry and TCRβ/γ clonal gene rearrangement test,confirmed the diagnosis of CD8+ITLPD-GI.CONCLUSION Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize.So far,indolent CD8+ITLPD-GI has not been comprehensively examined.The current mini-review focused on evaluating indolent CD8+ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis,detection of genetic and epigenetic alterations,and therapeutic target identification.
文摘Backgrounds and Purpose—In indolent non-Hodgkin lymphoma, histological transformation is a dramatic event which reduces the prognosis significantly. SUVmax values from FDG-PET/CT help differentiate between aggressive and indolent lymphomas, and transformed indolent lymphomas also show an increased FDG uptake. Possibly FDG uptake increases early in the clinical course and could predict histological transformation. Our objective was to predict histological transformation in indolent lymphomas from initial staging FDG-PET/CT. Patients and Methods—A retrospective study was performed. Patients with biopsy-proven indolent lymphoma who had had initial staging FDG-PET/CT were included. Qualitative (foci compared with FDG uptake liver) and semiquantitative (SUVmax-value per focus) analyses were performed of all abnormal foci. Patient characteristics and outcome were evaluated. Results—We included 88 patients, 5 of whom developed a histological transformation. Semiquantitative analysis showed a relation between maximum standardized uptake value and histological transformation (odds ratio 1.25, 95% CI 1.024 - 1.513). Qualitative analysis showed a negative predictive relation of FDG uptake less than or equal to liver in the occurrence of histological transformation. Transformation-free survival was 100% over 30 months in those with FDG uptake lower than or equal to liver. More FDG uptake than liver showed transformation-free survival of 88% over 30 months. Conclusion—Qualitative analysis of staging FDG-PET/CT in indolent lymphomas could be useful to rule out transformation in the next 30 months. In our study, semiquantitative analysis was statistically significantly associated with histological transformation and maximum standardized uptake value. However, because of the small number of patients, cautious interpretation of the results is warranted. More studies are needed to investigate the role of staging PET/CT in patient with indolent non-Hodkin lymphoma in the prediction of transformation.
文摘The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded （FFPE） tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.
文摘Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an uncommon subtype of EBV associated lymphoma usually characterized by aggressive clinical course. We report an atypical sinonasal ENKL case with long-lasting indolent behaviour, developed in the setting of a polymorphic EBV-associated lymphoproliferative disorder (LPD). A 52-year-old woman had suffered from chronic sinusitis and nasal obstruction since 2000, moderately worsened during the last years (marked enlargement of the sino-nasal mucosa at MRI in 2011) with elevated anti-VCA IgG and IgM titers. Three subsequent biopsies revealed slightly increasing morphophenotypic atypia, ranging from a polymorphic B- and T-cell EBV positive proliferation (diagnosed in 2011, but not fulfilling CAEBV diagnostic criteria) to an overt monomorphic mildly atypical T LPD without necrosis and angiocentricty diagnosed as ENKL in 2013 upon immunophenotype and TCR-γ gene clonal rearrangement. Clinically indolent ENKL with low-grade morphology is extremely rare and diagnostically challenging;while the few reports in the literature describe long-survival in ENKL treated patients comparing histologically neoplastic lesions at onset and recurrences, no reports are published on the slow progression from a polymorphic EBV-related T/NK proliferation to a histologically overt clinically indolent ENKL in an untreated patient who only received occasional steroid administration.
基金supported by the National Natural Science Foundation of China[grant number 8210031148]the Guangdong Basic and Applied Basic Research Foundation[grant number 2020A1515111087]the China Postdoctoral Science Foundation[grant number 2021M703750].
文摘Background:The natural disease course for patients with ulcerative colitis(UC)is heterogeneous and few data are available on the indolent course of UC and its related factors.We aimed to develop and validate a nomogramto predict indolent course in patients with UC.Methods:Data of patients diagnosed with UC in the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between April 2007 and February 2021 were retrospectively analysed.Indolent course was defined as a disease course without need for strict interventions(steroids,immunomodulators,biological agents,hospitalization,or surgery therapy)during the follow-up period.The whole cohort was randomly divided into training set and validation set.The nomogram was constructed in the training set based on the results of univariate and multivariate Cox regression analyses.The performance of the nomogram was assessed by the concordance index(C-index),area under the receiver-operating characteristic curve(AUC),and calibration plots.In addition,we internally validated the nomogramvia the bootstrap method and the validation set.Results:Of 969 treatment-naive patients with UC,771(79.6%)had an indolent course after diagnosis.Of these,313 patients were included in the development and validation of the nomogram.The nomogram incorporating age,disease activity,C-reactive protein,and platelet count showed good calibration and discrimination.The C-index was 0.759(0.741 in bootstrap validation)and the AUC at 2,4,and 6 years was 0.767,0.782,and 0.775,respectively.The nomogramperformed well when applied to the validation set.Conclusion:A majority of patients with UC had an indolent course after diagnosis.The nomogram developed in this study might be useful in therapeutic decision-making and follow-up management for patients with UC.
文摘Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.
文摘Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.
文摘multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.
文摘Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.
文摘Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and efficient synthetic approach was reported for access of a series of C2 or C3-(cycloheptatrienyl)-substituted indoles.A wide range of functional groups can be well tolerated in this transformation,especially including hydroxyl,halo,carboxylic acid and its derivative groups.Based on these results,a rational mechanism via electrophilic substitution of indoles with tropylium tetrafluoroborate is proposed.
基金supported by the National Key Research and Development Program of China(2023YFD1700500,2021YFD1700100)the National Natural Science Foundation of China(22177051,32061143045)+2 种基金the Fundamental Research Funds for the Central Universities(KYCYXT2022010)Sichuan Key Research and Development Program(22ZDYF0186,2021YFN0134)the College Student Research Training Program(202110307002T).
文摘As a natural alkaloid found extensively in cereal crops, gramine not only plays a crucial role in protecting barley and other grasses from various pests, but also reduces palatability for ruminants. Scientists are trying to figure out how gramine gets into cereal plants: is it inherently present or transformed through a special process? The latest study published in Science by Sara Leite Dias and co-authors, provides a detailed explanation. The starting point of the transformation is identified, and the transformation process is confirmed through rigorous experiments.
基金Supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(No.LR20C190001)the National Natural Science Foundation of China(No.42376103)+1 种基金the Natural Science Foundation of Ningbo City(No.2021J062)the K.C.Wong Magna Fund in Ningbo University。
文摘Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells specific to tetracycline in Vibrio splendidus were characterized.The tnaA Vs gene was first cloned and conditionally expressed in Escherichia coli Rosetta(DE3).To investigate the regulatory effect of TnaA Vs,the tnaA deletion strain AJ01/ΔtnaA was constructed by in-frame deletion.The undetected extracellular indole in the AJ01/ΔtnaA indicated that TnaA was the solo enzyme to produce indole in V.splendidus.The drop plate method showed that AJ01/ΔtnaA was more tolerant to the higher concentration of tetracycline than that of AJ01,being 340-fold higher in the proportion of survived cells when cell density OD 600≈0.65.Moreover,the synergistic effects of indole and tetracycline on killing of V.splendidus were determined.Results show that addition of 2-mmol/L indole increased the susceptibility of both AJ01 and AJ01/ΔtnaA to 10×minimum inhibitory concentration tetracycline.To explore the genes and pathways regulated by TnaA Vs,the transcriptomic analysis between AJ01 and AJ01/ΔtnaA was performed.Result shows that TCA cycle,arginine biosynthesis,quorum sensing and microbial metabolism in diverse environments were downregulated,while the ribosome pathways,the protein metabolic process,peptide biosynthetic and metabolic process were upregulated in the AJ01/ΔtnaA.This study shows that indole could enhance the bactericidal effect of tetracycline on V.splendidus by decreased ribosome level probably but increased ATP level.
基金supported by the National Key Research and Development Program of China(2022YFF1003003)the National Natural Science Foundation of China(32070333)the Key Research and Development Program of Yangling Seed Innovative Center(Ylzy-sc-04).
文摘Black spot,a fungal disease caused by Alternaria brassicae infection,inflicts severe damage on Chinese cabbage.Through comparative transcriptomic analysis,this study investigated the molecular mechanisms underlying Chinese cabbage’s defense responses to A.brassicae infection.Notably,we found that the expression of BrERF109 was induced by A.brassicae infection.Silencing of BrERF109 by an optimized virus-induced gene silencing(VIGS)assay in Chinese cabbage diminished disease resistance,while BrERF109-overexpression in Arabidopsis enhanced it.Additionally,BrERF109 silencing in Chinese cabbage suppressed indolic glucosinolates gene expression,substantially reducing indolic glucosinolates levels,whereas BrERF109-overexpression in Arabidopsis promoted their accumulation.BrERF109 directly interacts with the BrIGMT4 promoter,thereby facilitating indolic glucosinolates accumulation and enhancing defense against A.brassicae.This study elucidates the BrERF109-BrIGMT4 regulatory module in Chinese cabbage’s defense against A.brassicae infection,while providing valuable data for further investigation of plant-A.brassicae interactions.
基金the Qingdao Marine Science and Technology Center(No.2022QNLM030003-2)the Fundamental Research Funds for the Central Universities,Taishan Scholar Program of Shandong Province(No.tsqn202103152)National Natural Science Foundation of China(No.22171251) for financial support。
文摘The first total synthesis of(+)-taberdicatine B and(+)-tabernabovine B has been accomplished in 10steps with 26.9% overall yield and 15 steps with 7.3% overall yield,respectively.The prominent features of this efficient synthetic strategy include the following:(1)(+)-Taberdicatine B and(+)-tabernabovine B were accessed from common advanced intermediates by varying the substituents;(2) A one-pot asymmetric bromocyclization/hydrolysis was explored to assemble HPI skeleton;(3) Dieckmann condensation to form β-keto ester for the assembly of seven-membered ring;(4) An ester reduction/amide semireduction/cyclization sequence was applied to form the cage-like framework.
文摘AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.
基金Supported by The IGAR Initiative and the Clinical Trials Unit at the Cross Cancer Institute,which is supported in part by the Alberta Cancer Foundation
文摘AIM:To examine whether addition of 3T multiparametric magnetic resonance imaging(mp MRI)to an active surveillance protocol could detect aggressive or progressive prostate cancer.METHODS:Twenty-three patients with low risk disease were enrolled on this active surveillance study,all of which had Gleason score 6 or less disease.All patients had clinical assessments,including digital rectal examination and prostate specific antigen(PSA)testing,every 6 mo with annual 3T mp MRI scans with gadolinium contrast and minimum sextant prostate biopsies.The MRI images were anonymized of patient identifiers and clinical information and each scan underwentradiological review without the other results known.Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mp MRI to identify prostate cancer and progressive disease were calculated.RESULTS:During follow-up(median 24.8 mo)11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment.Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years.All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mp MRI scans at baseline(43.5% sensitivity).Aggressive disease prediction from baseline mpM RI scans had satisfactory specificity(81.8%)but low sensitivity(58.3%).Twentytwo patients had serial mp MRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy(30% specificity and 100% sensitivity).CONCLUSION:Addition of mp MRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.
文摘BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL)is extremely low,and the clinical symptoms are atypical,which makes it difficult to distinguish this disorder from Crohn's disease(CD),T lymphocyte proliferative disease,and other immune disorders.The misdiagnosis rate is high,and the patient's prognosis is poor.CASE SUMMARY In this case,the patient had repeated high fever,colonoscopy revealed multiple ulcers,and the initial diagnosis was CD.The patient’s condition did not improve after treatment with hormones and infliximab,and she eventually died.Positron emission tomographic-computed tomographic and B-ultrasound were performed in our hospital and showed that multiple lymph nodes were enlarged.Immunohistochemi-stry showed that CD3 and Epstein-Barr virus encoded RNA expression was positive.Colonoscopy,tissue biopsy,and histopathology showed intestinal focal mucosal infiltration of heterotypic lymphocytes with an abnormal immune phenotype.On the basis of the patient’s medical history,auxiliary examination,and pathological findings,digestive physicians and pathologists gave the diagnosis of NKTCL.CONCLUSION Clinicians need to improve their comprehensive knowledge of NKTCL,and combination of clinical symptoms,histological characteristics,as well as colonoscopy biopsies should be considered to improve the diagnosis and thereby reduce misdiagnosis.
基金New Teacher Foundation from Ministry of Education in China (Grant No.20090071120)Foundation of State Key Laboratory of Natural and Biomimetic Drugs (Grant No.K20100106)STCSM (Grant No.10431903200)
文摘A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer and human hepatic cancer cell lines, and compound 6, which is slightly different from 5 in its structure, showed good anticancer activity over human colorectal cancer cell line.
