Fc Receptor-Like 1(FCRL1),a member of the FCRL family,contains two immunoreceptor tyrosinebased activation motifs(ITAMs)in its cytoplasmic domain and plays a critical role in B-cell biology.Its expression begins in pr...Fc Receptor-Like 1(FCRL1),a member of the FCRL family,contains two immunoreceptor tyrosinebased activation motifs(ITAMs)in its cytoplasmic domain and plays a critical role in B-cell biology.Its expression begins in pre-B-cells,dynamically shifts during B-cell development,and contributes to the regulation of human B-cell activation.Notably,FCRL1 is overexpressed in subsets of naive and memory B-cells,as well as in malignant B-cells,including those in diffuse large B-cell lymphoma(DLBCL),an aggressive and often treatment-resistant hematological malignancy.Among FCRL family members,FCRL1 stands out as a promising immunotherapeutic target due to its selective expression in malignant B-cells and its functional role in proliferation.Given the limited efficacy of current therapies for relapsed/refractory DLBCL,targeting FCRL1 could address an unmet clinical need by offering a novel,mechanism-based approach to modulate B-cell signaling and enhance anti-tumor immunity.This mini-review highlights the therapeutic potential of FCRL1-directed strategies,supporting their further exploration in preclinical models and future clinical trials for DLBCL and other B-cell malignancies.展开更多
Elucidating the relationship between spin excitations and fermiology is essential for clarifying the pairing mechanism in iron-based superconductors(FeSCs).Here,we report inelastic neutron scattering results on the ho...Elucidating the relationship between spin excitations and fermiology is essential for clarifying the pairing mechanism in iron-based superconductors(FeSCs).Here,we report inelastic neutron scattering results on the hole overdoped Ba_(0.4)K_(0.6)Fe_(2)As_(2) near a Lifshitz transition,where the electron pocket at M point is nearly replaced by four hole pockets.In the normal state,the spin excitations is observed at incommensurate wave vectors with a chimney-like dispersion.By cooling down to the superconducting state,a neutron spin resonance mode emerges with a peak energy of Er=14-15 meV,weakly modulated along the L-direction.The incommensurability notably increases at low energies,giving rise to downward dispersions of the resonance mode.This behavior contrasts sharply with the upward dispersions of resonance observed in optimally doped Ba_(0.67)K_(0.33)Fe_(2)As_(2) contributed by the hole to electron scattering,but resembles those in KFe_(2)As_(2) and KCa_(2)Fe_(4)As_(4)F_(2) where the fermiology is dominated by hole pockets.These results highlight the critical role of electronic structure modifications near the Fermi level,especially in governing interband scattering under imperfect nesting conditions,which fundamentally shape the spin dynamics of FeSCs.展开更多
Wear is a prevalent issue across various industries. Spherical fused tungsten carbide (sFTC) reinforced nickel-aluminum bronze (NAB) matrix composite surface deposits have shown remarkable potential in mitigating wear...Wear is a prevalent issue across various industries. Spherical fused tungsten carbide (sFTC) reinforced nickel-aluminum bronze (NAB) matrix composite surface deposits have shown remarkable potential in mitigating wear by approximately 80%. However, the performance of these sFTC/NAB composite surface deposits is determined by their residual stress state, and the precise macroscopic and microscopic residual stresses within these composites have yet to be clearly established. To address this gap, we employed neutron diffraction to measure the residual stresses in the sFTC/NAB composite surface deposits and re-melted NAB samples produced via laser melt injection. Significant residual stresses were determined. The maximum tensile macro residual stress appears approximately 1-1.5 mm below the composite layer. Residual stresses accumulate with an increasing number of laser process tracks. The maximum tensile macro residual stress in the three-track samples reaches about 350 MPa. Preheating the base plate significantly reduces the levels of macroscopic residual stress. The WC phase displayed significant compressive thermal misfit residual stress magnitude, while the Cu matrix exhibited tensile thermal misfit residual stress. Preheating the base plate does not reduce microscopic thermal misfit residual stress levels. In addition, a finite element model was built to investigate temperature and residual stresses in the re-melted NAB samples. The predicted temperature history and residual stress agree with the experimental results.展开更多
The non-volatile multi-level magnetic or resistance states switching is extremely promising for newgeneration high-density information storage.In this work,we propose a novel multiple-state magnetic memory based on th...The non-volatile multi-level magnetic or resistance states switching is extremely promising for newgeneration high-density information storage.In this work,we propose a novel multiple-state magnetic memory based on the magnetic deflagration in a single Laves-phase Tb_(0.95)Mn_(1.5)Co_(0.5)compound with non-volatile and multilevel magnetic states switching.In consideration of the negative magnetization,six different magnetic states are achieved by simply applying the magnetic field.The abinitio calculations and neutron diffraction measurements indicate that the studied compound is a cubic structure withferromagnetic ordering at low temperature and the evolution in magnetic states(i.e.magnetic deflagration)should arise from the Barkhausen effect.The almost unchanged magnetic state under corresponding range of magnetic field enables the magnetization to be in the same magnitude even after 50 cyclic hysteresis loops.Furthermore,the retention,repeatable switching,and non-volatile characters of multi-level magnetic state have been primely confirmed.All these suggest that the Tb_(0.95)Mn_(1.5)Co_(0.5)compound with multiple magnetic deflagrations could be applied to multiple-state magnetic memory and this work would pave the way to design a novel multi-level magnetic storage.展开更多
BACKGROUND Approval of teduglutide is an important addition to the limited treatment options for short bowel syndrome(SBS).However,real-world evidence on teduglutide therapy for SBS in Latin America is scarce.AIM To i...BACKGROUND Approval of teduglutide is an important addition to the limited treatment options for short bowel syndrome(SBS).However,real-world evidence on teduglutide therapy for SBS in Latin America is scarce.AIM To investigate the effectiveness and safety of teduglutide in clinical practice in Argentina with a 24-week follow-up.METHODS This non-interventional multicentre cohort study included consecutive patients(aged≥1 years)with SBS who were dependent on parenteral support(PS)and received≥1 dose of teduglutide according to currently approved indications.RESULTS The study population(n=45)included 21 adult and 24 pediatric patients.The proportion of adult and pediatric patients who showed clinical response(defined as a≥20%reduction in weekly PS volume)after 24 weeks of treatment was 90.4%[95%confidence interval(CI):69.6%-98.8%]and 83.3%(95%CI:62.6%-95.2%),respectively.Overall,12 patients(26.6%;95%CI:14.6-41.9)were weaned from PS support at the 24-week assessment,6(28.5%;95%CI:11.5-52.1)in the adult cohort,and 6(25%;95%CI:9.7-46.7)in the pediatric cohort.Only baseline PS requirement was inversely associated with weaning from PS(P=0.025).The most frequently reported treatmentemergent adverse events(TEAEs)were mild to moderate abdominal pain and abdominal distension(16.6%;and 9.5%,respectively).None of the reported TEAEs led to treatment discontinuation.CONCLUSION This prospective real-world study demonstrated the effectiveness and safety of teduglutide in adult and pediatric patients with SBS in Argentina.The clinical response observed in both adults and pediatric patients was greater than that reported in phase 3 trials and was consistent with the results of other real-world studies.展开更多
AIM： To analyze the time interval （‘delay＇） between the first occurrence of clinical parameters associated with anastomotic leakage alter colorectal resection and subsequent relaparotomy. METHODS： In 36 out of 2...AIM： To analyze the time interval （‘delay＇） between the first occurrence of clinical parameters associated with anastomotic leakage alter colorectal resection and subsequent relaparotomy. METHODS： In 36 out of 289 consecutive patients with colorectal anastomosis, leakage was confirmed at relaparotomy. The medical records of these patients were retrospectively analysed and type and time of appearance of clinical parameters suggestive of anastomotic leakage were recorded. These parameters included heart rate, body temperature, local or generalized peritoneal reaction, leucocytosis, ileus and delayed gastric emptying. Factors influencing delay of relaparotomy and consequences of delayed recognition and treatment were determined. RESULTS： First documentation of at least one of the predefined parameters for anastomotic leakage was alter a median interval of 4 ± 1.7 d alter the operation. The median number of days between first parameter（s） associated with leakage and relaparotomy was 3.5 ± 5.7 d. The time interval between the first signs of leakage and relaparotomy was significantly longer when a weekend was included （4.2 d vs 2.4 d, P = 0.021） or radiological evaluation proved to be false-negative （8.1 d vs 3.5 d, P = 0.007）. No significant association between delay and number of additional relaparotomies, hospital stay or mortality could be demonstrated.CONCLUSION： An intervening weekend and negative diagnostic imaging reports may contribute to a delay in diagnosis and relaparotomy for anastomotic leakage. That delay was more than two days in two-thirds of the patients.展开更多
The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the...The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.展开更多
Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with d...Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome.展开更多
AIM: To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease (CD).
Immunoglobulin A （IgA） nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essen...Immunoglobulin A （IgA） nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identifed even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 （IgA1） with poor O-glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a “lanthanic” deposition remains to be clarifed. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarifed.展开更多
AIM:To assess the prevalence and location of ad-vanced neoplasia in patients undergoing colonoscopy,and to compare the yield per indication.METHODS:In a multicenter colonoscopy survey (n = 18 hospitals) in the Amsterd...AIM:To assess the prevalence and location of ad-vanced neoplasia in patients undergoing colonoscopy,and to compare the yield per indication.METHODS:In a multicenter colonoscopy survey (n = 18 hospitals) in the Amsterdam area (Northern Holland),data of all colonoscopies performed during a three month period in 2005 were analyzed. The location and the histological features of all colonic neoplasia were recorded. The prevalence and the distribution ofadvanced colorectal neoplasia and differences in yield between indication clusters were evaluated. Advanced neoplasm was defi ned as adenoma > 10 mm in size,with > 25% villous features or with high-grade dyspla-sia or cancer.RESULTS:A total of 4623 eligible patients underwent a total colonoscopy. The prevalence of advanced neo-plasia was 13%,with 281 (6%) adenocarcinomas and 342 (7%) advanced adenomas. Sixty-seven percent and 33% of advanced neoplasia were located in the distal and proximal colon,respectively. Of all patients with right-sided advanced neoplasia (n = 228),51% had a normal distal colon,whereas 27% had a syn-chronous distal adenoma. Ten percent of all colono-scopies were performed in asymptomatic patients,7% of whom had advanced neoplasia. In the respective procedure indication clusters,the prevalence of right-sided advanced neoplasia ranged from 11%-57%. CONCLUSION:One out of every 7-8 colonoscopies yielded an advanced colorectal neoplasm. Colonoscopy is warranted for the evaluation of both symptomatic and asymptomatic patients.展开更多
A 51-year-old man presented to our hospital with progressive pain and weakness in his right leg. Neurological examination revealed atrophy of all muscles of the right leg, unilateral foot drop and paralysis of the ant...A 51-year-old man presented to our hospital with progressive pain and weakness in his right leg. Neurological examination revealed atrophy of all muscles of the right leg, unilateral foot drop and paralysis of the anterior tibial and gastrocnemicus muscles. Electromyography confirmed a severe isolated sciatic neuropathy in the thigh. For unclear reasons, our patient habitually used to sit in a modified lotus position. We concluded that this position, in literature known as "lotus neuropathy" had resulted in the sciatic neuropathy. After more than a year our patient was referred again to our outpatient clinic. At that time there was only minimal improvement, now with an achilles tendon contracture and pes equinus due to immobility.展开更多
Complement cascade is involved in several renal diseases and in renal transplantation. The different components of the complement cascade might represent an optimal target for innovative therapies. In the frst section...Complement cascade is involved in several renal diseases and in renal transplantation. The different components of the complement cascade might represent an optimal target for innovative therapies. In the frst section of the paper the authors review the physiopathology of complement involvement in renal diseases and transplantation. In some cases this led to a reclassifcation of renal diseases moving from a histopathological to a physiopathologicalclassification. The principal issues afforded are： renal diseases with complement over activation, renal diseases with complement dysregulation, progression of renal diseases and renal transplantation. In the second section the authors discuss the several complement components that could represent a therapeutic target. Even if only the anti C5 monoclonal antibody is on the market, many targets as C1, C3, C5a and C5aR are the object of national or international trials. In addition, many molecules proved to be effective in vitro or in preclinical trials and are waiting to move to human trials in the future.展开更多
Immunoglobulin A nephropathy （IgAN） is characterized by different clinical manifestations and by long-term different outcomes. Major problem for the physicians is to understanding which patients are at risk of a dis...Immunoglobulin A nephropathy （IgAN） is characterized by different clinical manifestations and by long-term different outcomes. Major problem for the physicians is to understanding which patients are at risk of a disease evolution and to prescribe the right therapy to the right patients. Indeed, in addition to patients with a stable disease with no trend to evolution or even with a spontaneous recovery, patients with an active disease and patients with a rapidly evolving glomeru-lonephritis are described. Several histopathological, biological and clinical markers have been described and are currently used to a better understanding of patients at risk, to suggest the right therapy and to monitor the therapy effect and the IgAN evolution over time. The clinical markers are the most reliable and allow to divide the IgAN patients into three categories： The low risk patients, the intermediate risk patients and the high risk patients. Accordingly, the therapeutic measures range from no therapy with the only need of repeated controls, to supportive therapy eventually associated with low dose immunosuppression, to immunosuppressive treat-ment in the attempt to avoid the evolution to end stage renal disease. However the current evidence about the different therapies is still matter of discussion. New drugs are in the pipeline and are described. They are object of randomized controlled trials, but studies with a number of patients adequately powered and with a long follow up are needed to evaluate effcacy and safety of these new drugs.展开更多
This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genes...This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized： The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecifc treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in fnding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.展开更多
Objective: The purpose of this study was to determine the relative effects of pregnancy and mode of delivery on the prevalence of urinary and fecal incontinence. Study design: This was a prospective, observational mul...Objective: The purpose of this study was to determine the relative effects of pregnancy and mode of delivery on the prevalence of urinary and fecal incontinence. Study design: This was a prospective, observational multicenter study of women presenting to 6 gynecology clinics. Demographic data collected included: height, weight, gravidity, parity, and number of vaginal deliveries. Patients were diagnosed with incontinence by questionnaire. Standard univariate logistic regression analyses’ were performed to determine the contribution of pregnancy, mode of delivery, and BMI on the prevalence of urinary and fecal incontinence. Results: One thousand and four women were enrolled over an 18- month period. Two hundred and thirty-seven and 128 subjects had urinary and fecal incontinence, respectively. Odds ratio (95% CI) calculated for the prevalence of urinary incontinence by pregnancy and mode of delivery were: any term pregnancy vs no term pregnancy was 2.46 (1.53- 3.95), any term pregnancy but no vaginal deliveries (cesarean section only) vs no term pregnancy was 1.95 (0.99- 3.80), any term pregnancy and at least 1 vaginal delivery vs no term pregnancy was 2.53 (1.57- 4.07), and any term pregnancy but no vaginal delivery (cesarean section only) vs any term pregnancy, and at least 1 vaginal delivery was 1.30 (0.77- 3.95). Odds ratio (95% CI) calculated for the prevalence of fecal incontinence by pregnancy and mode of delivery were: any term pregnancy vs no term pregnancy was 2.26 (1.22- 4.19), any term pregnancy but no vaginal deliveries (cesarean section only) vs no term pregnancy was 1.13 (0.43- 2.96), any term pregnancy and at least 1 vaginal delivery vs no term pregnancy was 2.41 (1.30- 4.49), and any term pregnancy but no vaginal deliveries (cesarean section only) vs any term pregnancy, and at least 1 vaginal delivery was 2.15 (0.97- 4.77). BMI and age did not impact these results. Conclusion: Pregnancy increases the risk of urinary and fecal incontinence. Cesarean section does not decrease the risk of urinary or fecal incontinence compared to pregnancy with a vaginal delivery.展开更多
Objective: While interest in elective robotic surgery is growing, use in emergency setting remainslimited due to challenges posed by sicker patients, advanced pathology and logistical issues. During theCOVID-19 pandem...Objective: While interest in elective robotic surgery is growing, use in emergency setting remainslimited due to challenges posed by sicker patients, advanced pathology and logistical issues. During theCOVID-19 pandemic, robotic surgery could provide the benefit of having the surgeon away from thebedside and reducing the number of directly exposed medical staff. The objective of this study was toreport patient outcomes and initial learning experience of emergency robotic colorectal surgery duringthe COVID-19 pandemic.Methods: A case series study was conducted, including patients undergoing emergency robotic colorectalsurgery between February 2020 and February 2021 at Queen Alexandra Hospital in Portsmouth, UK.Patient data were collected from an ethics approved prospective database. Patient demographics,operative time, conversions and postoperative complications were recorded. In addition, readmissions,length of stay and short-term oncological outcomes were analyzed.Results: Ten patients with median age 64 y (range, 36-83 y) were included. Four patients had roboticcomplete mesocolic resection for obstructing cancers. Six had colorectal resections for benign disease inemergency setting. All were R0 with a mean lymph node harvest of 54 ± 13. Mean operative time was249 ± 117 min, the median length of stay was 9.4 d (range, 5-22 d). Only one patient was given atemporary diverting ileostomy. There were no grade III/V complications and no 30-day mortality.Conclusions: Provided an experienced team and peri-operative planning, emergency robotic colorectalsurgery can achieve favorable outcomes with benefits of radical lymph node dissection in oncologicalcases and avoidance of diverting stoma.展开更多
基金supported by funding from the Veterans Administration(I01 BX006101-01)supported in part by funding from the Veterans Administration(IO1 BX001262)the recipient of RCS Award(IK6 BX005964)from the Department of Veterans Administration.
文摘Fc Receptor-Like 1(FCRL1),a member of the FCRL family,contains two immunoreceptor tyrosinebased activation motifs(ITAMs)in its cytoplasmic domain and plays a critical role in B-cell biology.Its expression begins in pre-B-cells,dynamically shifts during B-cell development,and contributes to the regulation of human B-cell activation.Notably,FCRL1 is overexpressed in subsets of naive and memory B-cells,as well as in malignant B-cells,including those in diffuse large B-cell lymphoma(DLBCL),an aggressive and often treatment-resistant hematological malignancy.Among FCRL family members,FCRL1 stands out as a promising immunotherapeutic target due to its selective expression in malignant B-cells and its functional role in proliferation.Given the limited efficacy of current therapies for relapsed/refractory DLBCL,targeting FCRL1 could address an unmet clinical need by offering a novel,mechanism-based approach to modulate B-cell signaling and enhance anti-tumor immunity.This mini-review highlights the therapeutic potential of FCRL1-directed strategies,supporting their further exploration in preclinical models and future clinical trials for DLBCL and other B-cell malignancies.
基金supported by the National Key Research and Development Program of China(Grant Nos.2023YFA1406100,2018YFA0704200,2022YFA1403400 and 2021YFA1400400)the National Natural Science Foundation of China(Grant Nos.11822411 and 12274444)+2 种基金the Strategic Priority Research Program(B)of the CAS(Grant Nos.XDB25000000 and XDB33000000)K.C.Wong Education Foundation(GJTD-2020-01)AP by HBNI-RRCAT and MPCST under the FTYS program。
文摘Elucidating the relationship between spin excitations and fermiology is essential for clarifying the pairing mechanism in iron-based superconductors(FeSCs).Here,we report inelastic neutron scattering results on the hole overdoped Ba_(0.4)K_(0.6)Fe_(2)As_(2) near a Lifshitz transition,where the electron pocket at M point is nearly replaced by four hole pockets.In the normal state,the spin excitations is observed at incommensurate wave vectors with a chimney-like dispersion.By cooling down to the superconducting state,a neutron spin resonance mode emerges with a peak energy of Er=14-15 meV,weakly modulated along the L-direction.The incommensurability notably increases at low energies,giving rise to downward dispersions of the resonance mode.This behavior contrasts sharply with the upward dispersions of resonance observed in optimally doped Ba_(0.67)K_(0.33)Fe_(2)As_(2) contributed by the hole to electron scattering,but resembles those in KFe_(2)As_(2) and KCa_(2)Fe_(4)As_(4)F_(2) where the fermiology is dominated by hole pockets.These results highlight the critical role of electronic structure modifications near the Fermi level,especially in governing interband scattering under imperfect nesting conditions,which fundamentally shape the spin dynamics of FeSCs.
文摘Wear is a prevalent issue across various industries. Spherical fused tungsten carbide (sFTC) reinforced nickel-aluminum bronze (NAB) matrix composite surface deposits have shown remarkable potential in mitigating wear by approximately 80%. However, the performance of these sFTC/NAB composite surface deposits is determined by their residual stress state, and the precise macroscopic and microscopic residual stresses within these composites have yet to be clearly established. To address this gap, we employed neutron diffraction to measure the residual stresses in the sFTC/NAB composite surface deposits and re-melted NAB samples produced via laser melt injection. Significant residual stresses were determined. The maximum tensile macro residual stress appears approximately 1-1.5 mm below the composite layer. Residual stresses accumulate with an increasing number of laser process tracks. The maximum tensile macro residual stress in the three-track samples reaches about 350 MPa. Preheating the base plate significantly reduces the levels of macroscopic residual stress. The WC phase displayed significant compressive thermal misfit residual stress magnitude, while the Cu matrix exhibited tensile thermal misfit residual stress. Preheating the base plate does not reduce microscopic thermal misfit residual stress levels. In addition, a finite element model was built to investigate temperature and residual stresses in the re-melted NAB samples. The predicted temperature history and residual stress agree with the experimental results.
基金financially supported by the National Natural Science Foundation of China(No.52061014)the Natural Science Foundation of Henan Province(No.242300420352)+4 种基金the Key research and development program of Henan province(No.231111222200)the Key Scientific Research Projects of Higher Education Institutions in Henan Province(No.25CY025)the Leading Talents Program of Jiangxi Provincial Major Discipline Academic and Technical Leaders Training Program(No.20204BCJ22004)the Open Project awarded by Fujian Provincial Key Laboratory of Quantum Manipulation and New Energy Materials(No.QMNEM2002)Jiangxi Provincial Key Laboratory of Magnetic Metallic Materials and Devices(No.2024SSY05061)
文摘The non-volatile multi-level magnetic or resistance states switching is extremely promising for newgeneration high-density information storage.In this work,we propose a novel multiple-state magnetic memory based on the magnetic deflagration in a single Laves-phase Tb_(0.95)Mn_(1.5)Co_(0.5)compound with non-volatile and multilevel magnetic states switching.In consideration of the negative magnetization,six different magnetic states are achieved by simply applying the magnetic field.The abinitio calculations and neutron diffraction measurements indicate that the studied compound is a cubic structure withferromagnetic ordering at low temperature and the evolution in magnetic states(i.e.magnetic deflagration)should arise from the Barkhausen effect.The almost unchanged magnetic state under corresponding range of magnetic field enables the magnetization to be in the same magnitude even after 50 cyclic hysteresis loops.Furthermore,the retention,repeatable switching,and non-volatile characters of multi-level magnetic state have been primely confirmed.All these suggest that the Tb_(0.95)Mn_(1.5)Co_(0.5)compound with multiple magnetic deflagrations could be applied to multiple-state magnetic memory and this work would pave the way to design a novel multi-level magnetic storage.
基金Supported by Takeda Argentina SA,No.TAK-633-4003.
文摘BACKGROUND Approval of teduglutide is an important addition to the limited treatment options for short bowel syndrome(SBS).However,real-world evidence on teduglutide therapy for SBS in Latin America is scarce.AIM To investigate the effectiveness and safety of teduglutide in clinical practice in Argentina with a 24-week follow-up.METHODS This non-interventional multicentre cohort study included consecutive patients(aged≥1 years)with SBS who were dependent on parenteral support(PS)and received≥1 dose of teduglutide according to currently approved indications.RESULTS The study population(n=45)included 21 adult and 24 pediatric patients.The proportion of adult and pediatric patients who showed clinical response(defined as a≥20%reduction in weekly PS volume)after 24 weeks of treatment was 90.4%[95%confidence interval(CI):69.6%-98.8%]and 83.3%(95%CI:62.6%-95.2%),respectively.Overall,12 patients(26.6%;95%CI:14.6-41.9)were weaned from PS support at the 24-week assessment,6(28.5%;95%CI:11.5-52.1)in the adult cohort,and 6(25%;95%CI:9.7-46.7)in the pediatric cohort.Only baseline PS requirement was inversely associated with weaning from PS(P=0.025).The most frequently reported treatmentemergent adverse events(TEAEs)were mild to moderate abdominal pain and abdominal distension(16.6%;and 9.5%,respectively).None of the reported TEAEs led to treatment discontinuation.CONCLUSION This prospective real-world study demonstrated the effectiveness and safety of teduglutide in adult and pediatric patients with SBS in Argentina.The clinical response observed in both adults and pediatric patients was greater than that reported in phase 3 trials and was consistent with the results of other real-world studies.
文摘AIM： To analyze the time interval （‘delay＇） between the first occurrence of clinical parameters associated with anastomotic leakage alter colorectal resection and subsequent relaparotomy. METHODS： In 36 out of 289 consecutive patients with colorectal anastomosis, leakage was confirmed at relaparotomy. The medical records of these patients were retrospectively analysed and type and time of appearance of clinical parameters suggestive of anastomotic leakage were recorded. These parameters included heart rate, body temperature, local or generalized peritoneal reaction, leucocytosis, ileus and delayed gastric emptying. Factors influencing delay of relaparotomy and consequences of delayed recognition and treatment were determined. RESULTS： First documentation of at least one of the predefined parameters for anastomotic leakage was alter a median interval of 4 ± 1.7 d alter the operation. The median number of days between first parameter（s） associated with leakage and relaparotomy was 3.5 ± 5.7 d. The time interval between the first signs of leakage and relaparotomy was significantly longer when a weekend was included （4.2 d vs 2.4 d, P = 0.021） or radiological evaluation proved to be false-negative （8.1 d vs 3.5 d, P = 0.007）. No significant association between delay and number of additional relaparotomies, hospital stay or mortality could be demonstrated.CONCLUSION： An intervening weekend and negative diagnostic imaging reports may contribute to a delay in diagnosis and relaparotomy for anastomotic leakage. That delay was more than two days in two-thirds of the patients.
文摘The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.
文摘Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome.
文摘AIM: To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease (CD).
文摘Immunoglobulin A （IgA） nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identifed even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 （IgA1） with poor O-glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a “lanthanic” deposition remains to be clarifed. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarifed.
文摘AIM:To assess the prevalence and location of ad-vanced neoplasia in patients undergoing colonoscopy,and to compare the yield per indication.METHODS:In a multicenter colonoscopy survey (n = 18 hospitals) in the Amsterdam area (Northern Holland),data of all colonoscopies performed during a three month period in 2005 were analyzed. The location and the histological features of all colonic neoplasia were recorded. The prevalence and the distribution ofadvanced colorectal neoplasia and differences in yield between indication clusters were evaluated. Advanced neoplasm was defi ned as adenoma > 10 mm in size,with > 25% villous features or with high-grade dyspla-sia or cancer.RESULTS:A total of 4623 eligible patients underwent a total colonoscopy. The prevalence of advanced neo-plasia was 13%,with 281 (6%) adenocarcinomas and 342 (7%) advanced adenomas. Sixty-seven percent and 33% of advanced neoplasia were located in the distal and proximal colon,respectively. Of all patients with right-sided advanced neoplasia (n = 228),51% had a normal distal colon,whereas 27% had a syn-chronous distal adenoma. Ten percent of all colono-scopies were performed in asymptomatic patients,7% of whom had advanced neoplasia. In the respective procedure indication clusters,the prevalence of right-sided advanced neoplasia ranged from 11%-57%. CONCLUSION:One out of every 7-8 colonoscopies yielded an advanced colorectal neoplasm. Colonoscopy is warranted for the evaluation of both symptomatic and asymptomatic patients.
文摘A 51-year-old man presented to our hospital with progressive pain and weakness in his right leg. Neurological examination revealed atrophy of all muscles of the right leg, unilateral foot drop and paralysis of the anterior tibial and gastrocnemicus muscles. Electromyography confirmed a severe isolated sciatic neuropathy in the thigh. For unclear reasons, our patient habitually used to sit in a modified lotus position. We concluded that this position, in literature known as "lotus neuropathy" had resulted in the sciatic neuropathy. After more than a year our patient was referred again to our outpatient clinic. At that time there was only minimal improvement, now with an achilles tendon contracture and pes equinus due to immobility.
文摘Complement cascade is involved in several renal diseases and in renal transplantation. The different components of the complement cascade might represent an optimal target for innovative therapies. In the frst section of the paper the authors review the physiopathology of complement involvement in renal diseases and transplantation. In some cases this led to a reclassifcation of renal diseases moving from a histopathological to a physiopathologicalclassification. The principal issues afforded are： renal diseases with complement over activation, renal diseases with complement dysregulation, progression of renal diseases and renal transplantation. In the second section the authors discuss the several complement components that could represent a therapeutic target. Even if only the anti C5 monoclonal antibody is on the market, many targets as C1, C3, C5a and C5aR are the object of national or international trials. In addition, many molecules proved to be effective in vitro or in preclinical trials and are waiting to move to human trials in the future.
文摘Immunoglobulin A nephropathy （IgAN） is characterized by different clinical manifestations and by long-term different outcomes. Major problem for the physicians is to understanding which patients are at risk of a disease evolution and to prescribe the right therapy to the right patients. Indeed, in addition to patients with a stable disease with no trend to evolution or even with a spontaneous recovery, patients with an active disease and patients with a rapidly evolving glomeru-lonephritis are described. Several histopathological, biological and clinical markers have been described and are currently used to a better understanding of patients at risk, to suggest the right therapy and to monitor the therapy effect and the IgAN evolution over time. The clinical markers are the most reliable and allow to divide the IgAN patients into three categories： The low risk patients, the intermediate risk patients and the high risk patients. Accordingly, the therapeutic measures range from no therapy with the only need of repeated controls, to supportive therapy eventually associated with low dose immunosuppression, to immunosuppressive treat-ment in the attempt to avoid the evolution to end stage renal disease. However the current evidence about the different therapies is still matter of discussion. New drugs are in the pipeline and are described. They are object of randomized controlled trials, but studies with a number of patients adequately powered and with a long follow up are needed to evaluate effcacy and safety of these new drugs.
文摘This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized： The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecifc treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in fnding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.
文摘Objective: The purpose of this study was to determine the relative effects of pregnancy and mode of delivery on the prevalence of urinary and fecal incontinence. Study design: This was a prospective, observational multicenter study of women presenting to 6 gynecology clinics. Demographic data collected included: height, weight, gravidity, parity, and number of vaginal deliveries. Patients were diagnosed with incontinence by questionnaire. Standard univariate logistic regression analyses’ were performed to determine the contribution of pregnancy, mode of delivery, and BMI on the prevalence of urinary and fecal incontinence. Results: One thousand and four women were enrolled over an 18- month period. Two hundred and thirty-seven and 128 subjects had urinary and fecal incontinence, respectively. Odds ratio (95% CI) calculated for the prevalence of urinary incontinence by pregnancy and mode of delivery were: any term pregnancy vs no term pregnancy was 2.46 (1.53- 3.95), any term pregnancy but no vaginal deliveries (cesarean section only) vs no term pregnancy was 1.95 (0.99- 3.80), any term pregnancy and at least 1 vaginal delivery vs no term pregnancy was 2.53 (1.57- 4.07), and any term pregnancy but no vaginal delivery (cesarean section only) vs any term pregnancy, and at least 1 vaginal delivery was 1.30 (0.77- 3.95). Odds ratio (95% CI) calculated for the prevalence of fecal incontinence by pregnancy and mode of delivery were: any term pregnancy vs no term pregnancy was 2.26 (1.22- 4.19), any term pregnancy but no vaginal deliveries (cesarean section only) vs no term pregnancy was 1.13 (0.43- 2.96), any term pregnancy and at least 1 vaginal delivery vs no term pregnancy was 2.41 (1.30- 4.49), and any term pregnancy but no vaginal deliveries (cesarean section only) vs any term pregnancy, and at least 1 vaginal delivery was 2.15 (0.97- 4.77). BMI and age did not impact these results. Conclusion: Pregnancy increases the risk of urinary and fecal incontinence. Cesarean section does not decrease the risk of urinary or fecal incontinence compared to pregnancy with a vaginal delivery.
文摘Objective: While interest in elective robotic surgery is growing, use in emergency setting remainslimited due to challenges posed by sicker patients, advanced pathology and logistical issues. During theCOVID-19 pandemic, robotic surgery could provide the benefit of having the surgeon away from thebedside and reducing the number of directly exposed medical staff. The objective of this study was toreport patient outcomes and initial learning experience of emergency robotic colorectal surgery duringthe COVID-19 pandemic.Methods: A case series study was conducted, including patients undergoing emergency robotic colorectalsurgery between February 2020 and February 2021 at Queen Alexandra Hospital in Portsmouth, UK.Patient data were collected from an ethics approved prospective database. Patient demographics,operative time, conversions and postoperative complications were recorded. In addition, readmissions,length of stay and short-term oncological outcomes were analyzed.Results: Ten patients with median age 64 y (range, 36-83 y) were included. Four patients had roboticcomplete mesocolic resection for obstructing cancers. Six had colorectal resections for benign disease inemergency setting. All were R0 with a mean lymph node harvest of 54 ± 13. Mean operative time was249 ± 117 min, the median length of stay was 9.4 d (range, 5-22 d). Only one patient was given atemporary diverting ileostomy. There were no grade III/V complications and no 30-day mortality.Conclusions: Provided an experienced team and peri-operative planning, emergency robotic colorectalsurgery can achieve favorable outcomes with benefits of radical lymph node dissection in oncologicalcases and avoidance of diverting stoma.
