AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(...AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(DME).METHODS:This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy.Comprehensive clinical evaluation was performed,including slit-lamp examination,intraocular pressure(IOP)measurement,fluorescein and indocyanine green angiography(ICGA),and laboratory tests.Inflammatory responses were treated with topical or systemic corticosteroids,and patients were monitored for visual acuity and inflammatory activity.RESULTS:The incidence of IOI was 0.8%per patient(Innsbruck)and 0.23%(Czechia),with inflammation typically occurring between the third and sixth injection(mean interval:10d post-injection).Inflammator y presentations ranged from anterior uveitis to posterior segment involvement.One notable case demonstrated novel choroidal hypofluorescent lesions on angiography,suggesting deeper ocular involvement.The mean patient age was 76y;five of six affected patients were female.All cases responded to local and systemic corticosteroids,with full recovery of initial visual acuity.CONCLUSION:Sterile IOI after faricimab appears to be a rare but relevant adverse event.Although the incidence falls within expected ranges for anti-vascular endothelial growth factor(anti-VEGF)agents,the observed choroidal involvement represents a potentially new safety signal.Prompt diagnosis and corticosteroid therapy are effective in all cases.Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.展开更多
BACKGROUND Understanding the type and extent of coronary artery involvement in patients with acute type A aortic dissection(ATAAD)is vital for surgical planning.The Neri classification has been proposed as a guide for...BACKGROUND Understanding the type and extent of coronary artery involvement in patients with acute type A aortic dissection(ATAAD)is vital for surgical planning.The Neri classification has been proposed as a guide for surgical strategies,however,its prognostic impact on postoperative mortality rates remains understudied in large-scale cohorts.METHODS We reviewed 600 ATAAD patients who underwent surgery and coronary computed tomography angiography from 2016 to 2020 at Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China.Patients were classified based on the Neri classification system:no coronary artery involvement,type A(ostial involvement),type B(dissection in coronary body),and type C(circumferential detachment or complete avulsion).The primary endpoint was 30-day mortality.RESULTS Overall,28.3%of the patients had coronary artery involvement,with Neri type A,Neri type B,and Neri type C accounting for 13.3%,11.2%,and 3.8%,respectively.The right coronary artery was more frequently involved(25.3%)than the left coronary artery(8.0%).In the unadjusted analysis,patients with coronary artery involvement exhibited a numerically higher 30-day mortality compared to those without(5.3%vs.2.3%)(OR=2.35,95%CI:0.94–5.88,P=0.07),though this difference did not reach statistical significance.However,multivariable adjustment revealed significant association(adjusted OR=3.71,95%CI:1.05–13.13,P=0.04).Interestingly,after additional adjustment for coronary artery bypass grafting,the impact of coronary artery involvement on 30-day mortality no longer remained statistically significant(adjusted OR=3.13,95%CI:0.85–11.58,P=0.09).The 1-year mortality was higher in those with coronary artery involvement,but this significant association disappeared after adjusting for potential confounding variables.Furthermore,no significant difference in 30-day and 1-year mortality were observed among patients with different Neri classifications.CONCLUSIONS In patients with ATAAD who undergo surgery,the presence of coronary artery involvement is significantly associated with an increased risk of 30-day mortality.Proactive coronary artery bypass grafting may potentially mitigate the adverse impact of coronary artery involvement on 30-day mortality.展开更多
The immune system is involved in many age-related pathological changes,also plays an important role in tissue regeneration after injury.But no immune involvement has been discussed regarding cataract since it is presu...The immune system is involved in many age-related pathological changes,also plays an important role in tissue regeneration after injury.But no immune involvement has been discussed regarding cataract since it is presumed that lens has no source of immune cells as an avascular zone.Latest research has challenged the longstanding view of the lens as an immune-privileged tissue,revealing the presence of resident immune cells and active immune responses within the lens.Thus,we summarized the immune involvement in maintaining lens homeostasis,which may be a deleterious role in the induction of lens opacification if inappropriately activated.Furthermore,bioengineer-based immunomodulatory therapies to fine-tune the micro immune environment within lens may be future strategies for in situ lens regeneration,as a novel treatment for cataract.展开更多
Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives ...Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.展开更多
BACKGROUND In addition to nodal lesions,over 30%of mantle cell lymphomas(MCLs)also have gastrointestinal involvement,characteristically presenting as multiple lymphomatous polyposis(MLP),which rarely involve the esoph...BACKGROUND In addition to nodal lesions,over 30%of mantle cell lymphomas(MCLs)also have gastrointestinal involvement,characteristically presenting as multiple lymphomatous polyposis(MLP),which rarely involve the esophagus.Most related papers have been case reports,and no comprehensive studies have been conducted;thus,the actual clinical situation has remained unknown for a long time.AIM To elucidate the actual clinical situation of esophageal involvement of MCL presenting with MLP,including its prognosis.METHODS From January 2001 to December 2021,among MCL patients whose gastrointestinal lesions were histopathologically confirmed by endoscopic biopsy at our center,6 patients with MLP in the esophagus were selected.We retro-spectively examined the clinical features of these patients,including their prognosis.RESULTS In all patients,multiple lesions were present in the gastrointestinal tract other than the esophagus and in the lymph nodes throughout the body,and most patients also had lesions involving the bone marrow or spleen.Most of the treatments include chemotherapy,with a 50%survival period of less than 2 years and a 5-year survival rate of approximately 30%,indicating a poor prognosis.CONCLUSION Patients with esophageal involvement of the MCL who presented with MLP had a large tumor burden and poor survival.展开更多
Objective:To compare the diagnostic value of 99mTc-MDP SPECT/CT and MSCT in detecting thoracic wall and rib involvement in lung adenocarcinoma.Methods:A retrospective analysis was conducted on the imaging data of 78 t...Objective:To compare the diagnostic value of 99mTc-MDP SPECT/CT and MSCT in detecting thoracic wall and rib involvement in lung adenocarcinoma.Methods:A retrospective analysis was conducted on the imaging data of 78 thoracic wall and rib lesions from 66 patients,a total of 32 males and 34 females,aged(53.2±5.6)years old with pathologically confirmed lung adenocarcinoma who underwent both 99mTc-MDP SPECT/CT and MSCT examinations from March 2017 to September 2023.The diagnostic efficacy of the two imaging modalities was compared using pathological confirmation or clinical follow-up as the gold standard.Results:Pathological confirmation or clinical follow-up revealed 74 lesions with thoracic wall bone involvement in lung adenocarcinoma(20 lesions confirmed by surgical pathology and 54 lesions confirmed by clinical follow-up)and 4 lesions without thoracic wall or rib involvement(2 lesions confirmed by surgical pathology and 2 lesions confirmed by clinical follow-up).The diagnostic sensitivity,specificity,and accuracy of 99mTc-MDP SPECT/CT were 97.3%,50.0%,and 94.9%,respectively.Its diagnostic sensitivity and accuracy were higher than those of MSCT(72.3%and 74.4%,respectively),with statistically significant differences(P<0.05).The specificity of 99mTc-MDP SPECT/CT was lower than that of MSCT(100.0%),but the difference was not statistically significant(P<0.05).There were no statistically significant differences in the positive predictive value and negative predictive value between 99mTc-MDP SPECT/CT and MSCT(P>0.05).99mTc-MDP SPECT/CT examination revised the MSCT tumor staging in 14 patients[21.2%(14/66)]with lung adenocarcinoma.Conclusion:99mTc-MDP SPECT/CT imaging demonstrates superior diagnostic efficacy compared to MSCT in detecting thoracic wall and rib involvement in lung adenocarcinoma.It offers more accurate tumor staging than MSCT,and an accurate diagnosis aids in clinical treatment decision-making.展开更多
A 31-year-old woman with untreated hypertension presented with a progressively worsening occipital headache for 3 months.In the last 4 days,she developed a pulsating holocranial headache that awakened her nocturnally ...A 31-year-old woman with untreated hypertension presented with a progressively worsening occipital headache for 3 months.In the last 4 days,she developed a pulsating holocranial headache that awakened her nocturnally and worsened with Valsalva maneuver.Neurological examination revealed no focal deficits.The patient reported decreased visual acuity,and fundoscopic examination demonstrated grade III hypertensive retinopathy,but no optic disc edema.Blood pressure was 230/160 mmHg and laboratory analysis showed elevated serum creatinine(3.42 mg/dL).Autoimmune and infectious markers were negative.展开更多
Because human immunodeficiency virus(HIV)-associated Burkitt lymphoma(BL)has a poor prognosis new therapeutic approaches need to be developed1.Axicabtagene ciloleucel(axi-cel)is an anti-CD19 CAR-T cell commercially av...Because human immunodeficiency virus(HIV)-associated Burkitt lymphoma(BL)has a poor prognosis new therapeutic approaches need to be developed1.Axicabtagene ciloleucel(axi-cel)is an anti-CD19 CAR-T cell commercially available FDA-approved product for patients with relapsed or refractory(R/R)large B-cell lymphoma(LBCL).However,axi-cel has not been approved by the FDA for use in patients with R/R BL.展开更多
The purpose of the paper is to study retention of vocabulary acquired incidentally on task-induced involvement by senior middle school students. Grade two of senior middle students participated in the experiments, tes...The purpose of the paper is to study retention of vocabulary acquired incidentally on task-induced involvement by senior middle school students. Grade two of senior middle students participated in the experiments, testing whether retention of vocabulary acquired incidentally is contingent on amount of task-induced involvement.Using short-and long term, namely immediate posttest and delayed posttest, retention of twelve unfamiliar words was investigated in three learning tasks (reading, reading plus fill-in and writing) with varying degrees of “involvement load”- various combinations of need, search and evaluation. The results of the experiment partially support the Involvement Load Hypothesis: retention in the writing group was higher than that in the reading plus fill-in group; retention in the reading plus fill-in group was higher than that in the reading group. The results are discussed in light of the construct of task-induced involvement.展开更多
Background： The parent-to-child influences can be adaptive and contribute to the optimal psychological well-being and positive perception of the athlete. Contrary to the healthy parental involvement, a family can als...Background： The parent-to-child influences can be adaptive and contribute to the optimal psychological well-being and positive perception of the athlete. Contrary to the healthy parental involvement, a family can also have negative effects on an athlete development. The purpose of this study was to determine gender, father involvement, and mother involvement differences in the psychological profiles of collegiate freshmen athletes as measured by perfectionism, physical self-concept, and psychological well-being. Methods： Eighty-two male and 73 female collegiate freshmen responded to self-reported measures of family involvement, perfectionism, physical self-concept, and psychological well-being. Three separate 2 x 2 x 2 （gender x mother involvement x father involvement） factorial multivariate analysis of variance （MANOVAs） were carried out on the respective subscales from the reported measures. Results： There were significant differences for gender as well as father involvement in perfectionism （p 〈 0.01）. Freshmen females had lower concern over mistakes, and greater levels of organization as well as planfulness than males. Furthermore, freshmen athletes with high involved fathers showed greater levels of high standards for others as well as organization. Conclusion： Father involvement and mother involvement impact perfectionism, physical self-concept, and psychological well-being. perspective. extends through the freshmen year in college as shown in the athletes＇ Future research should develop better measures and utilize a family systems Copyright @ 2012, Shanghai University of Sport. Production and hosting by Elsevier B.V. All rights reserved展开更多
Inflammatory bowel disease (IBD) has been associated with either clinical or subclinical airway and parenchymal lung involvement and interstitial lung complications. Several studies have reported that atopy has a high...Inflammatory bowel disease (IBD) has been associated with either clinical or subclinical airway and parenchymal lung involvement and interstitial lung complications. Several studies have reported that atopy has a high prevalence in IBD patients. Overlapping allergic disorders seem to be present in both the respiratory and gastrointestinal systems. The purpose of this review is to update clinicians on recent available literature and to discuss the need for a highly suspicious approach by clinicians.展开更多
Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclona...Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.展开更多
The Dof(DNA-binding with one finger)protein family spans a group of plant transcription factors involved in the regulation of several functions,such as plant responses to stress,hormones and light,phytochrome signalin...The Dof(DNA-binding with one finger)protein family spans a group of plant transcription factors involved in the regulation of several functions,such as plant responses to stress,hormones and light,phytochrome signaling and seed germination.Here we describe the Dof-like gene family in grapevine(Vitis vinifera L.),which consists of 25 genes coding for Dof.An extensive in silico characterization of the VviDofL gene family was performed.Additionally,the expression of the entire gene family was assessed in 54 grapevine tissues and organs using an integrated approach with microarray(cv Corvina)and real-time PCR(cv Pinot Noir)analyses.The phylogenetic analysis comparing grapevine sequences with those of Arabidopsis,tomato,poplar and already described Dof genes in other species allowed us to identify several duplicated genes.The diversification of grapevine DofL genes during evolution likely resulted in a broader range of biological roles.Furthermore,distinct expression patterns were identified between samples analyzed,corroborating such hypothesis.Our expression results indicate that several VviDofL genes perform their functional roles mainly during flower,berry and seed development,highlighting their importance for grapevine growth and production.The identification of similar expression profiles between both approaches strongly suggests that these genes have important regulatory roles that are evolutionally conserved between grapevine cvs Corvina and Pinot Noir.展开更多
Crohn's disease(CD) is a chronic idiopathic inflammatory disease of gastrointestinal tract characterizedby segmental and transmural involvement of gastrointestinal tract. Ileocolonic and colonic/anorectal is a mos...Crohn's disease(CD) is a chronic idiopathic inflammatory disease of gastrointestinal tract characterizedby segmental and transmural involvement of gastrointestinal tract. Ileocolonic and colonic/anorectal is a most common and account for 40% of cases and involvement of small intestine is about 30%. Isolated involvement of stomach is an extremely unusual presentation of the disease accounting for less than 0.07% of all gastrointestinal CD. To date there are only a few documented case reports of adults with isolated gastric CD and no reports in the pediatric population. The diagnosis is difficult to establish in such cases with atypical presentation. In the absence of any other source of disease and in the presence of nonspecific upper gastrointestinal endoscopy and histological findings, serological testing can play a vital role in the diagnosis of atypical CD. Recent studies have suggested that perinuclear anti-neutrophil cytoplasmic antibody and anti-Saccharomycescervisia antibody may be used as additional diagnostic tools. The effectiveness of infliximab in isolated gastric CD is limited to only a few case reports of adult patients and the long-term outcome is unknown.展开更多
The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved ...The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor （AATF）, PARP-1, and phosphorylated H2AX （v-H2AX） were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-l-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, y-H2AX expression increased to 265%. Co-immunoprecipitation （co-IP） assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly（ADP-ribosyl）ation {PARylation） regulated AATF expression, in conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.展开更多
The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
Bone morphogenetic proteins （Bmp） are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown...Bone morphogenetic proteins （Bmp） are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmprla in the osteoblast lineage with Dmpl-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation. Because expression of sclerostin （SOST）, a secreted Wnt antagonist, is notably reduced in the Bmprla- deficient osteocytes, we have genetically tested the hypothesis that increased Wnt signaling might mediate the increase in cancellous bone formation in response to Bmprla deletion. Forced expression of human SOST from a Dmpl promoter fragment partially rescues preosteoblast hyperproliferation and cancellous bone overgrowth in the Bmprla mutant mice, demonstrating functional interaction between Bmp and Wnt signaling in the cancellous bone compat^a-tent. To test whether increased Wnt signaling can compensate for the defect in periosteal growth caused by Bmprla deletion, we have generated compound mutants harboring a hyperactive mutation （A214V） in the Wnt receptor Lrp5. However, the mutant Lrp5 does not restore periosteal bone growth in the Bmprla-deficient mice. Thus, Bmp signaling restricts cancellous bone accrual partly through induction of SOST that limits preosteoblast proliferation, but promotes periosteal bone growth apparently independently of Wnt activation.展开更多
Senescence leads to declines in fruit quality and shortening of shelf life.It is known that low temperatures(LTs)efficiently delay fruit senescence and that high temperatures(HTs)accelerate senescence.However,the mole...Senescence leads to declines in fruit quality and shortening of shelf life.It is known that low temperatures(LTs)efficiently delay fruit senescence and that high temperatures(HTs)accelerate senescence.However,the molecular mechanism by which temperature affects senescence is unclear.Herein,through multiomics analyses of fruits subjected to postharvest HT,LT,and room temperature treatments,a total of 56 metabolic compounds and 700 mRNAs were identified to be associated with fruit senescence under HT or LT conditions.These compounds could be divided into antisenescent(I→III)and prosenescent(IV→VI)types.HT affected the expression of 202 mRNAs to enhance the biosynthesis of prosenescent compounds of types V and VI and to inhibit the accumulation of antisenescent compounds of types II and III.LT affected the expression of 530 mRNAs to promote the accumulation of antisenescent compounds of types I and II and to impede the biosynthesis of prosenescent compounds of types IV and V.Moreover,16 microRNAs were isolated in response to HT or LT conditions and interacted with the mRNAs associated with fruit senescence under HT or LT conditions.Transient transformation of pear fruit showed that one of these microRNAs,Novel_188,can mediate fruit senescence by interacting with its target Pbr027651.1.Thus,both HT and LT conditions can affect fruit senescence by affecting microRNA–mRNA interactions,but the molecular networks are different in pear fruit.展开更多
BACKGROUND Simultaneous cerebral and myocardial infarction with arterial involvement has not been reported in hypereosinophilic syndrome(HES).Here,we report a patient with HES that was also associated with acute ische...BACKGROUND Simultaneous cerebral and myocardial infarction with arterial involvement has not been reported in hypereosinophilic syndrome(HES).Here,we report a patient with HES that was also associated with acute ischemic stroke,myocardial infarction,and arterial involvement of the left common carotid artery,vertebral arteries,posterior cerebral artery,and coronary artery.CASE SUMMARY A 64-year-old male patient was admitted with headache and right lower extremity weakness.Laboratory tests indicated eosinophilia.Brain magnetic resonance imaging(MRI)showed bilateral and multiple acute infarcts in the border zones.Electrocardiography revealed that T wave was inverted and that the concentration of troponin I was significantly elevated above normal levels.Cardiac echocardiography showed an ejection fraction of 69%with mitral and tricuspid mild regurgitation.Computed tomography angiography detected multiple and localized instances of mild stenosis in the left common carotid artery bifurcation,bilateral vertebral arteries(V5 segment),and the posterior cerebral artery(P2 segment).These were observed together with multiple non-calcified and mixed plaques as well as luminal stenosis in the left circumflex artery,left anterior descending artery,and right coronary artery.The patient was treated with oral methylprednisolone and clopidogrel,after which the absolute eosinophil count fell rapidly to a normal level.After one month,a second brain MRI showed a partial reduction in the size and number of the lesions.CONCLUSION HES can masquerade as ischemic stroke,myocardial infarction,and arterial vascular involvement.The patient reported here recovered very quickly when his eosinophil blood count returned to normal.Early diagnosis and rapid reduction of eosinophils may lead to a good prognosis.展开更多
Objective： Extranodal involvement represents a peculiar presentation of diffuse large B-cell lymphoma（DLBCL）. Previous studies have suggested that older patients are more prone to extranodal involvement. This study...Objective： Extranodal involvement represents a peculiar presentation of diffuse large B-cell lymphoma（DLBCL）. Previous studies have suggested that older patients are more prone to extranodal involvement. This study retrospectively addressed the distribution, prognostic value and treatment options of extranodal involvement in young patients with DLBCL.Methods： A total of 329 patients were enrolled according to the inclusion requirements. The effects of gender,extranodal involvement, age-adjusted international prognostic index（aa IPI）, rituximab infusion and radiotherapy on patient outcomes were evaluated.Results： Among these patients, 59% presented extranodal involvement in 16 anatomic sites. More than one instance was linked to many poorer clinical characteristics and poorer survival compared with either nodal disease or one instance. In patients with one extranodal lesion, multivariate analysis revealed that the site of extranodal involvement, but not the aa IPI or rituximab infusion, was independently related to the outcome, and radiotherapy had a negative influence on survival.Conclusions： Extranodal involvement is common in younger patients and exhibits a ubiquitous distribution.The site of extranodal involvement is of strong prognostic significance. Radiotherapy for extranodal lesions does not improve patient outcomes.展开更多
文摘AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(DME).METHODS:This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy.Comprehensive clinical evaluation was performed,including slit-lamp examination,intraocular pressure(IOP)measurement,fluorescein and indocyanine green angiography(ICGA),and laboratory tests.Inflammatory responses were treated with topical or systemic corticosteroids,and patients were monitored for visual acuity and inflammatory activity.RESULTS:The incidence of IOI was 0.8%per patient(Innsbruck)and 0.23%(Czechia),with inflammation typically occurring between the third and sixth injection(mean interval:10d post-injection).Inflammator y presentations ranged from anterior uveitis to posterior segment involvement.One notable case demonstrated novel choroidal hypofluorescent lesions on angiography,suggesting deeper ocular involvement.The mean patient age was 76y;five of six affected patients were female.All cases responded to local and systemic corticosteroids,with full recovery of initial visual acuity.CONCLUSION:Sterile IOI after faricimab appears to be a rare but relevant adverse event.Although the incidence falls within expected ranges for anti-vascular endothelial growth factor(anti-VEGF)agents,the observed choroidal involvement represents a potentially new safety signal.Prompt diagnosis and corticosteroid therapy are effective in all cases.Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.
基金supported by the National High Level Hospital Clinical Research Funding(No.2024-GSP-TJ-15&No.2023-GSP-QN-17)the Chinese Society of Cardiology’s Foundation(CSCF2023B03).
文摘BACKGROUND Understanding the type and extent of coronary artery involvement in patients with acute type A aortic dissection(ATAAD)is vital for surgical planning.The Neri classification has been proposed as a guide for surgical strategies,however,its prognostic impact on postoperative mortality rates remains understudied in large-scale cohorts.METHODS We reviewed 600 ATAAD patients who underwent surgery and coronary computed tomography angiography from 2016 to 2020 at Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China.Patients were classified based on the Neri classification system:no coronary artery involvement,type A(ostial involvement),type B(dissection in coronary body),and type C(circumferential detachment or complete avulsion).The primary endpoint was 30-day mortality.RESULTS Overall,28.3%of the patients had coronary artery involvement,with Neri type A,Neri type B,and Neri type C accounting for 13.3%,11.2%,and 3.8%,respectively.The right coronary artery was more frequently involved(25.3%)than the left coronary artery(8.0%).In the unadjusted analysis,patients with coronary artery involvement exhibited a numerically higher 30-day mortality compared to those without(5.3%vs.2.3%)(OR=2.35,95%CI:0.94–5.88,P=0.07),though this difference did not reach statistical significance.However,multivariable adjustment revealed significant association(adjusted OR=3.71,95%CI:1.05–13.13,P=0.04).Interestingly,after additional adjustment for coronary artery bypass grafting,the impact of coronary artery involvement on 30-day mortality no longer remained statistically significant(adjusted OR=3.13,95%CI:0.85–11.58,P=0.09).The 1-year mortality was higher in those with coronary artery involvement,but this significant association disappeared after adjusting for potential confounding variables.Furthermore,no significant difference in 30-day and 1-year mortality were observed among patients with different Neri classifications.CONCLUSIONS In patients with ATAAD who undergo surgery,the presence of coronary artery involvement is significantly associated with an increased risk of 30-day mortality.Proactive coronary artery bypass grafting may potentially mitigate the adverse impact of coronary artery involvement on 30-day mortality.
基金Supported by the National Natural Science Foundation of China(No.82271063No.82471054)Central Guidance for Local Scientific and Technological Development Funding Projects(No.2024ZY01057).
文摘The immune system is involved in many age-related pathological changes,also plays an important role in tissue regeneration after injury.But no immune involvement has been discussed regarding cataract since it is presumed that lens has no source of immune cells as an avascular zone.Latest research has challenged the longstanding view of the lens as an immune-privileged tissue,revealing the presence of resident immune cells and active immune responses within the lens.Thus,we summarized the immune involvement in maintaining lens homeostasis,which may be a deleterious role in the induction of lens opacification if inappropriately activated.Furthermore,bioengineer-based immunomodulatory therapies to fine-tune the micro immune environment within lens may be future strategies for in situ lens regeneration,as a novel treatment for cataract.
基金supported by the National Natural Science Foundation of China,Nos.82071426,81873784Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DF)。
文摘Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.
文摘BACKGROUND In addition to nodal lesions,over 30%of mantle cell lymphomas(MCLs)also have gastrointestinal involvement,characteristically presenting as multiple lymphomatous polyposis(MLP),which rarely involve the esophagus.Most related papers have been case reports,and no comprehensive studies have been conducted;thus,the actual clinical situation has remained unknown for a long time.AIM To elucidate the actual clinical situation of esophageal involvement of MCL presenting with MLP,including its prognosis.METHODS From January 2001 to December 2021,among MCL patients whose gastrointestinal lesions were histopathologically confirmed by endoscopic biopsy at our center,6 patients with MLP in the esophagus were selected.We retro-spectively examined the clinical features of these patients,including their prognosis.RESULTS In all patients,multiple lesions were present in the gastrointestinal tract other than the esophagus and in the lymph nodes throughout the body,and most patients also had lesions involving the bone marrow or spleen.Most of the treatments include chemotherapy,with a 50%survival period of less than 2 years and a 5-year survival rate of approximately 30%,indicating a poor prognosis.CONCLUSION Patients with esophageal involvement of the MCL who presented with MLP had a large tumor burden and poor survival.
文摘Objective:To compare the diagnostic value of 99mTc-MDP SPECT/CT and MSCT in detecting thoracic wall and rib involvement in lung adenocarcinoma.Methods:A retrospective analysis was conducted on the imaging data of 78 thoracic wall and rib lesions from 66 patients,a total of 32 males and 34 females,aged(53.2±5.6)years old with pathologically confirmed lung adenocarcinoma who underwent both 99mTc-MDP SPECT/CT and MSCT examinations from March 2017 to September 2023.The diagnostic efficacy of the two imaging modalities was compared using pathological confirmation or clinical follow-up as the gold standard.Results:Pathological confirmation or clinical follow-up revealed 74 lesions with thoracic wall bone involvement in lung adenocarcinoma(20 lesions confirmed by surgical pathology and 54 lesions confirmed by clinical follow-up)and 4 lesions without thoracic wall or rib involvement(2 lesions confirmed by surgical pathology and 2 lesions confirmed by clinical follow-up).The diagnostic sensitivity,specificity,and accuracy of 99mTc-MDP SPECT/CT were 97.3%,50.0%,and 94.9%,respectively.Its diagnostic sensitivity and accuracy were higher than those of MSCT(72.3%and 74.4%,respectively),with statistically significant differences(P<0.05).The specificity of 99mTc-MDP SPECT/CT was lower than that of MSCT(100.0%),but the difference was not statistically significant(P<0.05).There were no statistically significant differences in the positive predictive value and negative predictive value between 99mTc-MDP SPECT/CT and MSCT(P>0.05).99mTc-MDP SPECT/CT examination revised the MSCT tumor staging in 14 patients[21.2%(14/66)]with lung adenocarcinoma.Conclusion:99mTc-MDP SPECT/CT imaging demonstrates superior diagnostic efficacy compared to MSCT in detecting thoracic wall and rib involvement in lung adenocarcinoma.It offers more accurate tumor staging than MSCT,and an accurate diagnosis aids in clinical treatment decision-making.
文摘A 31-year-old woman with untreated hypertension presented with a progressively worsening occipital headache for 3 months.In the last 4 days,she developed a pulsating holocranial headache that awakened her nocturnally and worsened with Valsalva maneuver.Neurological examination revealed no focal deficits.The patient reported decreased visual acuity,and fundoscopic examination demonstrated grade III hypertensive retinopathy,but no optic disc edema.Blood pressure was 230/160 mmHg and laboratory analysis showed elevated serum creatinine(3.42 mg/dL).Autoimmune and infectious markers were negative.
基金supported by the Sponsored by Tianjin Health Research Project(Grant No.TJWJ2023ZD003)the Chinese Society of Clinical Oncology Beijing Xisike Clinical Oncology Research Foundation(Grant Nos.Y-NCJH202201-0027 and Y-2022YMJN/MS-0001).
文摘Because human immunodeficiency virus(HIV)-associated Burkitt lymphoma(BL)has a poor prognosis new therapeutic approaches need to be developed1.Axicabtagene ciloleucel(axi-cel)is an anti-CD19 CAR-T cell commercially available FDA-approved product for patients with relapsed or refractory(R/R)large B-cell lymphoma(LBCL).However,axi-cel has not been approved by the FDA for use in patients with R/R BL.
文摘The purpose of the paper is to study retention of vocabulary acquired incidentally on task-induced involvement by senior middle school students. Grade two of senior middle students participated in the experiments, testing whether retention of vocabulary acquired incidentally is contingent on amount of task-induced involvement.Using short-and long term, namely immediate posttest and delayed posttest, retention of twelve unfamiliar words was investigated in three learning tasks (reading, reading plus fill-in and writing) with varying degrees of “involvement load”- various combinations of need, search and evaluation. The results of the experiment partially support the Involvement Load Hypothesis: retention in the writing group was higher than that in the reading plus fill-in group; retention in the reading plus fill-in group was higher than that in the reading group. The results are discussed in light of the construct of task-induced involvement.
文摘Background： The parent-to-child influences can be adaptive and contribute to the optimal psychological well-being and positive perception of the athlete. Contrary to the healthy parental involvement, a family can also have negative effects on an athlete development. The purpose of this study was to determine gender, father involvement, and mother involvement differences in the psychological profiles of collegiate freshmen athletes as measured by perfectionism, physical self-concept, and psychological well-being. Methods： Eighty-two male and 73 female collegiate freshmen responded to self-reported measures of family involvement, perfectionism, physical self-concept, and psychological well-being. Three separate 2 x 2 x 2 （gender x mother involvement x father involvement） factorial multivariate analysis of variance （MANOVAs） were carried out on the respective subscales from the reported measures. Results： There were significant differences for gender as well as father involvement in perfectionism （p 〈 0.01）. Freshmen females had lower concern over mistakes, and greater levels of organization as well as planfulness than males. Furthermore, freshmen athletes with high involved fathers showed greater levels of high standards for others as well as organization. Conclusion： Father involvement and mother involvement impact perfectionism, physical self-concept, and psychological well-being. perspective. extends through the freshmen year in college as shown in the athletes＇ Future research should develop better measures and utilize a family systems Copyright @ 2012, Shanghai University of Sport. Production and hosting by Elsevier B.V. All rights reserved
文摘Inflammatory bowel disease (IBD) has been associated with either clinical or subclinical airway and parenchymal lung involvement and interstitial lung complications. Several studies have reported that atopy has a high prevalence in IBD patients. Overlapping allergic disorders seem to be present in both the respiratory and gastrointestinal systems. The purpose of this review is to update clinicians on recent available literature and to discuss the need for a highly suspicious approach by clinicians.
基金the National Natural Science Foundation of China(Nos.81800201 and 81872322)the Zhejiang Key Research and Development Project(No.2020C03014)the Key Project of Zhejiang Provincial Natural Science Foundation of China(No.LZ22H160009)。
文摘Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.
基金This work was supported by‘Coordenação de Aperfeiçoamento de Pessoal de Nível Superior’(CAPES,Brazil),‘Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,Brazil,Proc.475440/2004-8,GP research fellowship 311361/2009-9),‘Fundação de AmparoàPesquisa do Estado do Rio Grande do Sul’(FAPERGS,Brazil,Proc.04/1184.6)and Embrapa(Brazil).
文摘The Dof(DNA-binding with one finger)protein family spans a group of plant transcription factors involved in the regulation of several functions,such as plant responses to stress,hormones and light,phytochrome signaling and seed germination.Here we describe the Dof-like gene family in grapevine(Vitis vinifera L.),which consists of 25 genes coding for Dof.An extensive in silico characterization of the VviDofL gene family was performed.Additionally,the expression of the entire gene family was assessed in 54 grapevine tissues and organs using an integrated approach with microarray(cv Corvina)and real-time PCR(cv Pinot Noir)analyses.The phylogenetic analysis comparing grapevine sequences with those of Arabidopsis,tomato,poplar and already described Dof genes in other species allowed us to identify several duplicated genes.The diversification of grapevine DofL genes during evolution likely resulted in a broader range of biological roles.Furthermore,distinct expression patterns were identified between samples analyzed,corroborating such hypothesis.Our expression results indicate that several VviDofL genes perform their functional roles mainly during flower,berry and seed development,highlighting their importance for grapevine growth and production.The identification of similar expression profiles between both approaches strongly suggests that these genes have important regulatory roles that are evolutionally conserved between grapevine cvs Corvina and Pinot Noir.
文摘Crohn's disease(CD) is a chronic idiopathic inflammatory disease of gastrointestinal tract characterizedby segmental and transmural involvement of gastrointestinal tract. Ileocolonic and colonic/anorectal is a most common and account for 40% of cases and involvement of small intestine is about 30%. Isolated involvement of stomach is an extremely unusual presentation of the disease accounting for less than 0.07% of all gastrointestinal CD. To date there are only a few documented case reports of adults with isolated gastric CD and no reports in the pediatric population. The diagnosis is difficult to establish in such cases with atypical presentation. In the absence of any other source of disease and in the presence of nonspecific upper gastrointestinal endoscopy and histological findings, serological testing can play a vital role in the diagnosis of atypical CD. Recent studies have suggested that perinuclear anti-neutrophil cytoplasmic antibody and anti-Saccharomycescervisia antibody may be used as additional diagnostic tools. The effectiveness of infliximab in isolated gastric CD is limited to only a few case reports of adult patients and the long-term outcome is unknown.
基金supported by grants from the National Natural Science Foundation of China(8120223181273116+2 种基金81430079)the Science and Technology Program of Guangdong Bureau of Science and TechnologyChina(2013B021800069)
文摘The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor （AATF）, PARP-1, and phosphorylated H2AX （v-H2AX） were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-l-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, y-H2AX expression increased to 265%. Co-immunoprecipitation （co-IP） assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly（ADP-ribosyl）ation {PARylation） regulated AATF expression, in conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.
文摘The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
基金supported by NIH grants AR060456 and AR055923(FL)partly supported by P30 AR057235(Washington University Musculoskeletal Research Center)+1 种基金supported by the George O’Brien Center for Kidney Disease Research(P30 DK079333)Kidney translational Research Core and the Renal Division at the Washington University School of Medicine
文摘Bone morphogenetic proteins （Bmp） are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmprla in the osteoblast lineage with Dmpl-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation. Because expression of sclerostin （SOST）, a secreted Wnt antagonist, is notably reduced in the Bmprla- deficient osteocytes, we have genetically tested the hypothesis that increased Wnt signaling might mediate the increase in cancellous bone formation in response to Bmprla deletion. Forced expression of human SOST from a Dmpl promoter fragment partially rescues preosteoblast hyperproliferation and cancellous bone overgrowth in the Bmprla mutant mice, demonstrating functional interaction between Bmp and Wnt signaling in the cancellous bone compat^a-tent. To test whether increased Wnt signaling can compensate for the defect in periosteal growth caused by Bmprla deletion, we have generated compound mutants harboring a hyperactive mutation （A214V） in the Wnt receptor Lrp5. However, the mutant Lrp5 does not restore periosteal bone growth in the Bmprla-deficient mice. Thus, Bmp signaling restricts cancellous bone accrual partly through induction of SOST that limits preosteoblast proliferation, but promotes periosteal bone growth apparently independently of Wnt activation.
基金supported by the Key Program of the National Natural Science Foundation of China(31830081)the Natural Science Foundation of China(31672118)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20171380)the Earmarked Fund for China Agriculture Research System(CARS-28).
文摘Senescence leads to declines in fruit quality and shortening of shelf life.It is known that low temperatures(LTs)efficiently delay fruit senescence and that high temperatures(HTs)accelerate senescence.However,the molecular mechanism by which temperature affects senescence is unclear.Herein,through multiomics analyses of fruits subjected to postharvest HT,LT,and room temperature treatments,a total of 56 metabolic compounds and 700 mRNAs were identified to be associated with fruit senescence under HT or LT conditions.These compounds could be divided into antisenescent(I→III)and prosenescent(IV→VI)types.HT affected the expression of 202 mRNAs to enhance the biosynthesis of prosenescent compounds of types V and VI and to inhibit the accumulation of antisenescent compounds of types II and III.LT affected the expression of 530 mRNAs to promote the accumulation of antisenescent compounds of types I and II and to impede the biosynthesis of prosenescent compounds of types IV and V.Moreover,16 microRNAs were isolated in response to HT or LT conditions and interacted with the mRNAs associated with fruit senescence under HT or LT conditions.Transient transformation of pear fruit showed that one of these microRNAs,Novel_188,can mediate fruit senescence by interacting with its target Pbr027651.1.Thus,both HT and LT conditions can affect fruit senescence by affecting microRNA–mRNA interactions,but the molecular networks are different in pear fruit.
文摘BACKGROUND Simultaneous cerebral and myocardial infarction with arterial involvement has not been reported in hypereosinophilic syndrome(HES).Here,we report a patient with HES that was also associated with acute ischemic stroke,myocardial infarction,and arterial involvement of the left common carotid artery,vertebral arteries,posterior cerebral artery,and coronary artery.CASE SUMMARY A 64-year-old male patient was admitted with headache and right lower extremity weakness.Laboratory tests indicated eosinophilia.Brain magnetic resonance imaging(MRI)showed bilateral and multiple acute infarcts in the border zones.Electrocardiography revealed that T wave was inverted and that the concentration of troponin I was significantly elevated above normal levels.Cardiac echocardiography showed an ejection fraction of 69%with mitral and tricuspid mild regurgitation.Computed tomography angiography detected multiple and localized instances of mild stenosis in the left common carotid artery bifurcation,bilateral vertebral arteries(V5 segment),and the posterior cerebral artery(P2 segment).These were observed together with multiple non-calcified and mixed plaques as well as luminal stenosis in the left circumflex artery,left anterior descending artery,and right coronary artery.The patient was treated with oral methylprednisolone and clopidogrel,after which the absolute eosinophil count fell rapidly to a normal level.After one month,a second brain MRI showed a partial reduction in the size and number of the lesions.CONCLUSION HES can masquerade as ischemic stroke,myocardial infarction,and arterial vascular involvement.The patient reported here recovered very quickly when his eosinophil blood count returned to normal.Early diagnosis and rapid reduction of eosinophils may lead to a good prognosis.
基金supported by the National Nature Science Foundation of China (No. 81071938, 81470365)
文摘Objective： Extranodal involvement represents a peculiar presentation of diffuse large B-cell lymphoma（DLBCL）. Previous studies have suggested that older patients are more prone to extranodal involvement. This study retrospectively addressed the distribution, prognostic value and treatment options of extranodal involvement in young patients with DLBCL.Methods： A total of 329 patients were enrolled according to the inclusion requirements. The effects of gender,extranodal involvement, age-adjusted international prognostic index（aa IPI）, rituximab infusion and radiotherapy on patient outcomes were evaluated.Results： Among these patients, 59% presented extranodal involvement in 16 anatomic sites. More than one instance was linked to many poorer clinical characteristics and poorer survival compared with either nodal disease or one instance. In patients with one extranodal lesion, multivariate analysis revealed that the site of extranodal involvement, but not the aa IPI or rituximab infusion, was independently related to the outcome, and radiotherapy had a negative influence on survival.Conclusions： Extranodal involvement is common in younger patients and exhibits a ubiquitous distribution.The site of extranodal involvement is of strong prognostic significance. Radiotherapy for extranodal lesions does not improve patient outcomes.
