Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacologica...With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacological therapy of AD.Photobiomodulation(PBM)is non-pharmacological approach that has shown very promising results in the therapy of AD in pilot clinical and animal studies.However,the mechanisms of therapeutic efects of PBM for AD are poorly understood.In this study on mice,we demonstrate that photodynamic efects of 5-aminolevulenic acid and laser 635 nm cause reduction of network of the meningeal lymphatic vessels(MLVs)leading to suppression of lymphatic removal of beta-amyloid(Aβ)from the right lateral ventricle and the hippocampus.Using the original protocol of PBM under electroencephalographic monitoring of wakefulness and sleep stages in non-anesthetized mice,we discover that the 7-day course of PBM during deep sleep vs.wakefulness provides better restoration of clearance of Aβfrom the ventricular system of the brain and the hippocampus.Our results shed light on the mechanism of PBM and show the stimulating efects of PBM on the brain lymphatic drainage that promotes transport of Aβvia the lymphatic pathway.The efects of PBM on the brain lymphatics in sleeping brain open a new niche in the study of restorative functions of sleep as well as it is an important informative platform for the development of innovative smart sleep technologies for the therapy of AD.展开更多
Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen so...Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.展开更多
Lymphatic-venous anastomosis(LVA)surgery has recently emerged as a potential treatment for Alzheimer’s disease(AD)in China.This minimally invasive microsurgical procedure has been used for decades to treat lymphoedem...Lymphatic-venous anastomosis(LVA)surgery has recently emerged as a potential treatment for Alzheimer’s disease(AD)in China.This minimally invasive microsurgical procedure has been used for decades to treat lymphoedema,typically in the limbs,to decompress blocked lymphatic drainage pathways.展开更多
The unidirectional flow of lymphatic fluid depends significantly on the valve structure within the lymphatic system,thus impacting tumor cell metastasis via the lymphatic system.However,existing microdevices for study...The unidirectional flow of lymphatic fluid depends significantly on the valve structure within the lymphatic system,thus impacting tumor cell metastasis via the lymphatic system.However,existing microdevices for studying tumor lymphatic metastasis have overlooked the impact of open-close valve structures on the lymphatic flow field.This paper presents a novel biomimetic lymphatic valve structure,which innovatively incorporates the thin-shell theory into the modeling of lymphatic-mimicking structures.Through finite element simulations,we have systematically analyzed the influence of valve thickness and elasticity on its deformation characteristics.Materials closely matching the actual properties of biological tissues are synthesized.And the soft-etching technique was used to fabricate lymphomimetic microchannels,which were then tested to evaluate their capability in intercepting unidirectional flow.The results showed that the lymphomimetic valve structure had no observable leaks and effectively intercepted unidirectional flow.Our study not only elucidates the mechanism of lymphatic circulation but also presents a dependable biomimetic model that could facilitate additional biological investigations and phenotypic drug screening.展开更多
Background: Puffy hand syndrome (PHS) is a rare complication primarily associated with intravenous drug use (IVDU), characterized by chronic swelling and fibrosis of the hands due to lymphatic damage. Concurrent pulmo...Background: Puffy hand syndrome (PHS) is a rare complication primarily associated with intravenous drug use (IVDU), characterized by chronic swelling and fibrosis of the hands due to lymphatic damage. Concurrent pulmonary complications, such as pneumonia and pneumothorax, significantly contribute to increased morbidity in this population. Case Presentation: We report the case of a 28-year-old female who injects drugs, and presents with fever, bilateral hand edema, and respiratory symptoms. Clinical evaluation revealed erythema and edema of both hands, elevated inflammatory markers, and a left lower lobe infiltration that progressed to pneumothorax. A diagnosis of PHS and left lower lobe pneumonia complicated by pneumothorax was established. Management and Outcomes: The patient was treated with broad-spectrum antibiotics, including ceftriaxone, levofloxacin, dexamethasone, and oxygen supplementation, as well as antipyretics. She demonstrated partial clinical improvement and was referred to another hospital’s thoracic surgery department for specialized care. Conclusions: This case underscores the importance of early recognition and multidisciplinary management of rare but serious complications in IVDU patients. Further research is necessary to elucidate the interplay between lymphatic dysfunction and pulmonary pathophysiology in this demographic.展开更多
BACKGROUND Chylous ascites(CA),which is characterized by lymphatic leakage into the peritoneal cavity,is a rare but significant complication of liver transplantation.Although dietary and pharmacological strategies hav...BACKGROUND Chylous ascites(CA),which is characterized by lymphatic leakage into the peritoneal cavity,is a rare but significant complication of liver transplantation.Although dietary and pharmacological strategies have shown effectiveness in managing CA,standardized treatment protocols have yet to be established.AIMTo evaluate the comparative effectiveness of low-fat diet (LFD) enriched with medium-chain triglycerides (MCTs)vs octreotide therapy in managing post-liver transplantation CA.METHODSA comprehensive literature review was conducted to analyze the outcomes of dietary interventions and octreotidetherapy. The key parameters examined included resolution rates, treatment duration, and recurrence.RESULTSA comprehensive literature search yielded 13 studies that met the inclusion criteria, comprising 4 retrospectivecohort studies and 8 case studies. The incidence of CA following liver transplantation ranges from 0.6% to 4.7%.The onset varied, with a median time to diagnosis of 10 days after transplantation. A LFD with MCT supplementationwas used as the first-line therapy in 83.3% of the studies, with resolution rates ranging from 62.5% to100%. Octreotide therapy was utilized in 66.7% of the studies, primarily as a second-line therapy, with resolutionrates of 83.3% to 100%. Combination therapy showed a significantly higher resolution rate than did dietarymanagement alone (97.8% vs 78.9%, P = 0.02). The time to resolution was significantly shorter with octreotidecontainingregimens than with dietary management alone (median, 7 days vs 14 days;P = 0.03).CONCLUSIONA stepwise approach to CA management is recommended, initiating dietary interventions and escalating tooctreotide when necessary. Further research through well-designed randomized controlled trials is essential toestablish standardized treatment protocols for optimizing patient outcomes.展开更多
The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer&#...The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.In this study,we employed dual-contrast functionalphotoacoustic microscopy to evaluate the impact of lipopolysaccharide-induced central nervous system inflammation on brain lymphatic function and to explore the protective effects of the P2X7 receptor(P2X7R)antagonist.Our findings demonstrated that lipopolysac-charide intervention led to impaired function of the meningeal lymphatic vessels,which was par-tially restored by the P2X7R antagonist,whereas its effects on the glymphatic system and cerebral vessels were minimal.This study further supports the feasibility of photoacoustic microscopy for assessing brain lymphatic function and highlights the therapeutic potential of P2X7R antagonism.These findings suggest that P2X7R may serve as a key target for modulating brain-lymphatic interactions,providing an experimental foundation for developing intervention strategies for neuroinflammatory and neurodegenerative diseases.展开更多
Mild cognitive impairment(MCI),which is a high-risk transitional phase leading to Alzheimer’s disease,is characterized by mild memory deficits and specific cognitive dysfunctions.Without effective intervention,a sign...Mild cognitive impairment(MCI),which is a high-risk transitional phase leading to Alzheimer’s disease,is characterized by mild memory deficits and specific cognitive dysfunctions.Without effective intervention,a significant proportion of patients with MCI progress to dementia.However,current pharmacological treatments are characterized by side effects and poor patient compliance.Therefore,it is necessary to develop effective,noninvasive alternative treatments.Repetitive transcranial magnetic stimulation(rTMS)is becoming a widely studied noninvasive treatment for central nervous system disease.The therapeutic effects of rTMS on patients with MCI and its underlying mechanism are noteworthy issues.Recently,a growing number of studies have shown that meningeal lymphatic vessel damage may be related to cognitive dysfunction.Whether the improvement of the meningeal lymphatic system is an important mechanism through which rTMS improves the clinical manifestations of MCI is worthy of further study.展开更多
BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicat...BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicator,typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes.Contralateral axillary metastasis(CAM)without ipsilateral involvement is exceedingly rare,particularly in early-stage breast cancer.This report presents a case of CAM in a patient with triple-negative breast cancer(TNBC),underscoring diagnostic and therapeutic complexities.CASE SUMMARY A 73-year-old female presented with left-sided early-stage IDC in February 2023.Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes,a postoperative positron emission tomography(PET)scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla.Biopsy confirmed metastatic ductal carcinoma with triple-negative status,resulting in an upstaged diagnosis of metastatic breast cancer,stage IV,M1.The patient underwent six cycles of adjuvant chemotherapy,with follow-up PET imaging showing regression of the contralateral lesion.This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.CONCLUSION This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.展开更多
Intestinal lymphangiectasia(IL)is characterized by the dilation of intestinal lymphatic vessels,which can rupture and cause loss of lymph into the intestine.Due to the high content of proteins,lipoproteins,and lymphoc...Intestinal lymphangiectasia(IL)is characterized by the dilation of intestinal lymphatic vessels,which can rupture and cause loss of lymph into the intestine.Due to the high content of proteins,lipoproteins,and lymphocytes in the intestinal lymph,loss of lymph might result in hypoproteinemia,hypoalbuminemia,hypogammaglobulinemia,and lymphocytopenia.In addition,there may be a depletion of minerals,lipids,and fat-soluble vitamins.IL can be primary due to inherent malfunctioning of the lymphatic system,or secondly,a result of various factors that may hinder lymphatic drainage either directly or indirectly.This condition has emerged as a subject of significant clinical interest.Given that the intestinal lymphatic system plays an important role in the body’s fluid homeostasis,adaptive immunity,nutrient and drug absorption,intestinal transport,and systemic metabolism,its dysfunction may have wider implications.Although primary IL is rare,with varied clinical features,complications,treatment response,and outcomes,secondary IL is more common than previously believed.The definitive diagnosis of IL requires endoscopic demonstration of whitish villi(which frequently resemble snowflakes)and histological confirmation of dilated lacteals in the small intestinal mucosa.Treatment of IL is challenging and involves dietary modifications,managing underlying medical conditions,and using medications such as sirolimus and octreotide.Recognizing its prevalence and diverse etiology is crucial for targeted management of this challenging medical condition.This article provides a comprehensive exploration of the clinical implications associated with IL.In addition,it offers valuable insights into critical knowledge gaps in the existing diagnostic and management landscape.展开更多
Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposit...Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposits,accelerating the onset and progression of Alzheimer’s disease(AD).12 Given that cervical lymph nodes receive cerebrospinal fluid from the brain’s glymphatic system,34 we speculated that decompression of the lymphatic trunk and cervical lymphatic-venous anastomosis(LVA)could facilitate the flow of cerebrospinal fluid in the cranial glymphatic system,potentially accelerating the clearance of harmful beta-amyloid and tau proteins.We collaborated with surgeons who specialise in LVA supermicrosurgery for maxillofacial tumours and lymphoedema to develop a procedure to relieve the blockage of the glymphatic system.This surgery employs supermicrosurgery techniques to create LVA connecting the bilateral cervical,deep lymphatic vessels to the veins,resulting in lymphatic trunk decompression,which allows the lymph fluid in the high-pressure lymphatic vessels to flow into the low-pressure venous system.The goal of the minimally invasive surgery is to enhance the removal of proteins,such as beta-amyloid and tau,from the brain’s lymphatic systems to the maxillofacial lymphatic vessels,unclogging protein blockages within the brain.This extracranial procedure is safer than intracranial approaches.展开更多
Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biolog...Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.展开更多
BACKGROUND This study presents an evaluation of the computed tomography lymphangio-graphy(CTL)features of lymphatic plastic bronchitis(PB)and primary chylotho-rax to improve the diagnostic accuracy for these two disea...BACKGROUND This study presents an evaluation of the computed tomography lymphangio-graphy(CTL)features of lymphatic plastic bronchitis(PB)and primary chylotho-rax to improve the diagnostic accuracy for these two diseases.AIM To improve the diagnosis of lymphatic PB or primary chylothorax,a retrospective analysis of the clinical features and CTL characteristics of 71 patients diagnosed with lymphatic PB or primary chylothorax was performed.METHODS The clinical and CTL data of 71 patients(20 with lymphatic PB,41 with primary chylothorax,and 10 with lymphatic PB with primary chylothorax)were collected retrospectively.CTL was performed in all patients.The clinical manifestations,CTL findings,and conventional chest CT findings of the three groups of patients were compared.The chi-square test or Fisher's exact test was used to compare the differences among the three groups.A difference was considered to be statistically significant when P<0.05.RESULTS(1)The percentages of abnormal contrast medium deposits on CTL in the three groups were as follows:Thoracic duct outlet in 14(70.0%),33(80.5%)and 8(80.0%)patients;peritracheal region in 18(90.0%),15(36.6%)and 8(80.0%)patients;pleura in 6(30.0%),33(80.5%)and 9(90.0%)patients;pericardium in 6(30.0%),6(14.6%)and 4(40.0%)patients;and hilum in 16(80.0%),11(26.8%)and 7(70.0%)patients;and(2)the abnormalities on conven-tional chest CT in the three groups were as follows:Ground-glass opacity in 19(95.0%),18(43.9%)and 8(80.0%)patients;atelectasis in 4(20.0%),26(63.4%)and 7(70.0%)patients;interlobular septal thickening in 12(60.0%),11(26.8%)and 3(30.0%)patients;bronchovascular bundle thickening in 14(70.0%),6(14.6%)and 4(40.0%)patients;localized mediastinal changes in 14(70.0%),14(34.1%),and 7(70.0%)patients;diffuse mediastinal changes in 6(30.0%),5(12.2%),and 3(30.0%)patients;cystic lesions in the axilla in 2(10.0%),6(14.6%),and 2(20.0%)patients;and cystic lesions in the chest wall in 0(0%),2(4.9%),and 2(4.9%)patients.CONCLUSION CTL is well suited to clarify the characteristics of lymphatic PB and primary chylothorax.This method is an excellent tool for diagnosing these two diseases.展开更多
The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are...The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.展开更多
In this editorial,we discuss the clinical implications of the article“Lymphatic plastic bronchitis and primary chylothorax:A study based on computed tomography lymphangiography”published by Li et al.Pulmonary lympha...In this editorial,we discuss the clinical implications of the article“Lymphatic plastic bronchitis and primary chylothorax:A study based on computed tomography lymphangiography”published by Li et al.Pulmonary lymphatic disorders involve abnormalities in the lymphatic tissues within the thoracic cavity.Specifically,pulmonary lymphatic perfusion syndrome describes a condition where the flow of lymphatic fluid in the lungs is redirected towards abnormally widened lymphatic vessels.Clinically,individuals with this syn-drome may experience symptoms such as chyloptysis,plastic bronchitis(PB),chylothorax,chylopericardium,and interstitial lung disease.These disorders can be caused by various factors,including PB,chylothorax,and complex lymphatic malformations.Advancements in lymphatic imaging techniques,such as in-tranodal lymphangiography,computed tomography lymphangiography,and dynamic contrast-enhanced magnetic resonance lymphangiography,have enabled the detection of abnormal lymphatic flow.This has enhanced our understanding of the pathophysiology of these conditions.Additionally,innovative minimally invasive treatments,such as thoracic duct embolization,selective embolization of lymphatic channels,and surgical procedures aim to improve clinical condition of patients and address their dietary needs.展开更多
Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolyti...Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely investigated.In this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of GSD.Compared to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in OCPs.In the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in vitro.Using an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo.We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like phenotypes.Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the control.Based on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.展开更多
Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of can...Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system.展开更多
Objective:The possible enhancing effect of anlotinib on programmed death receptor ligand(PD-L1)antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium,including lymphatic endothelial cells(LEC...Objective:The possible enhancing effect of anlotinib on programmed death receptor ligand(PD-L1)antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium,including lymphatic endothelial cells(LECs)and blood endothelial cells(BECs),were determined to identify patients who would benefit from this treatment.Methods:PD-L1 positivity in LECs,BECs,and tumor cells(TCs)was assessed using paraffin sections with multicolor immunofluorescence in an investigator’s brochure clinical trial of TQB2450(PD-L1 antibody)alone or in combination with anlotinib in patients with non-small cell lung cancer.Progression-free survival(PFS)with different levels of PD-L1 expression was compared between the two groups.Results:Among 75 patients,the median PFS(mPFS)was longer in patients who received TQB2450 with anlotinib[10 and 12 mg(161 and 194 days,respectively)]than patients receiving TQB2450 alone(61 days)[hazard ratio(HR)_(10 mg)=0.390(95%confidence interval{CI},0.201–0.756),P=0.005;HR_(12 mg)=0.397(0.208–0.756),P=0.005].The results were similar among 58 patients with high PD-L1 expression in LECs and TCs[159 and 209 vs.82 days,HR_(10 mg)=0.445(0.210–0.939),P=0.034;HR_(12 mg)=0.369(0.174–0.784),P=0.009],and 53 patients with high PD-L1 expression in BECs and TCs[161 and 209 vs.41 days,HR_(10 mg)=0.340(0.156–0.742),P=0.007;HR_(12 mg)=0.340(0.159–0.727),P=0.005].No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases.Conclusions:Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs.Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs,which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.展开更多
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
基金We thank research center“Symbiosis”and immunochemistry laboratory IBPPM RAS for their support with immunofuorescence analysis and confocal microscopy within Project No.GR 121031100266-3SGO,FI,SA,BI,TA,DA,ZM,ED,AV,EA,VV,TA,KV,MM,and MA were supported by grant(No.23-75-30001)+1 种基金the Russian Science Foundation,DA and ED were supported by Grant(No.21-75-10088)the Russian Science Foundation and by Grant from the Russian Ministry of Science and High Education(No.075-15-2022-1094).
文摘With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacological therapy of AD.Photobiomodulation(PBM)is non-pharmacological approach that has shown very promising results in the therapy of AD in pilot clinical and animal studies.However,the mechanisms of therapeutic efects of PBM for AD are poorly understood.In this study on mice,we demonstrate that photodynamic efects of 5-aminolevulenic acid and laser 635 nm cause reduction of network of the meningeal lymphatic vessels(MLVs)leading to suppression of lymphatic removal of beta-amyloid(Aβ)from the right lateral ventricle and the hippocampus.Using the original protocol of PBM under electroencephalographic monitoring of wakefulness and sleep stages in non-anesthetized mice,we discover that the 7-day course of PBM during deep sleep vs.wakefulness provides better restoration of clearance of Aβfrom the ventricular system of the brain and the hippocampus.Our results shed light on the mechanism of PBM and show the stimulating efects of PBM on the brain lymphatic drainage that promotes transport of Aβvia the lymphatic pathway.The efects of PBM on the brain lymphatics in sleeping brain open a new niche in the study of restorative functions of sleep as well as it is an important informative platform for the development of innovative smart sleep technologies for the therapy of AD.
基金supported by National Key Research and Development Program of China(Grant No.2021YFE0115200)the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Grant No.U22A20356).
文摘Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
基金the Ministry of Science and Technology of the People's Republic of China(2021ZD0201804,GW)the National Natural Science Foundation of China(82371416,HW).
文摘Lymphatic-venous anastomosis(LVA)surgery has recently emerged as a potential treatment for Alzheimer’s disease(AD)in China.This minimally invasive microsurgical procedure has been used for decades to treat lymphoedema,typically in the limbs,to decompress blocked lymphatic drainage pathways.
基金supported by National Natural Science Foundation of National Key Research and Development Program of China(2020YFB2009002).
文摘The unidirectional flow of lymphatic fluid depends significantly on the valve structure within the lymphatic system,thus impacting tumor cell metastasis via the lymphatic system.However,existing microdevices for studying tumor lymphatic metastasis have overlooked the impact of open-close valve structures on the lymphatic flow field.This paper presents a novel biomimetic lymphatic valve structure,which innovatively incorporates the thin-shell theory into the modeling of lymphatic-mimicking structures.Through finite element simulations,we have systematically analyzed the influence of valve thickness and elasticity on its deformation characteristics.Materials closely matching the actual properties of biological tissues are synthesized.And the soft-etching technique was used to fabricate lymphomimetic microchannels,which were then tested to evaluate their capability in intercepting unidirectional flow.The results showed that the lymphomimetic valve structure had no observable leaks and effectively intercepted unidirectional flow.Our study not only elucidates the mechanism of lymphatic circulation but also presents a dependable biomimetic model that could facilitate additional biological investigations and phenotypic drug screening.
文摘Background: Puffy hand syndrome (PHS) is a rare complication primarily associated with intravenous drug use (IVDU), characterized by chronic swelling and fibrosis of the hands due to lymphatic damage. Concurrent pulmonary complications, such as pneumonia and pneumothorax, significantly contribute to increased morbidity in this population. Case Presentation: We report the case of a 28-year-old female who injects drugs, and presents with fever, bilateral hand edema, and respiratory symptoms. Clinical evaluation revealed erythema and edema of both hands, elevated inflammatory markers, and a left lower lobe infiltration that progressed to pneumothorax. A diagnosis of PHS and left lower lobe pneumonia complicated by pneumothorax was established. Management and Outcomes: The patient was treated with broad-spectrum antibiotics, including ceftriaxone, levofloxacin, dexamethasone, and oxygen supplementation, as well as antipyretics. She demonstrated partial clinical improvement and was referred to another hospital’s thoracic surgery department for specialized care. Conclusions: This case underscores the importance of early recognition and multidisciplinary management of rare but serious complications in IVDU patients. Further research is necessary to elucidate the interplay between lymphatic dysfunction and pulmonary pathophysiology in this demographic.
文摘BACKGROUND Chylous ascites(CA),which is characterized by lymphatic leakage into the peritoneal cavity,is a rare but significant complication of liver transplantation.Although dietary and pharmacological strategies have shown effectiveness in managing CA,standardized treatment protocols have yet to be established.AIMTo evaluate the comparative effectiveness of low-fat diet (LFD) enriched with medium-chain triglycerides (MCTs)vs octreotide therapy in managing post-liver transplantation CA.METHODSA comprehensive literature review was conducted to analyze the outcomes of dietary interventions and octreotidetherapy. The key parameters examined included resolution rates, treatment duration, and recurrence.RESULTSA comprehensive literature search yielded 13 studies that met the inclusion criteria, comprising 4 retrospectivecohort studies and 8 case studies. The incidence of CA following liver transplantation ranges from 0.6% to 4.7%.The onset varied, with a median time to diagnosis of 10 days after transplantation. A LFD with MCT supplementationwas used as the first-line therapy in 83.3% of the studies, with resolution rates ranging from 62.5% to100%. Octreotide therapy was utilized in 66.7% of the studies, primarily as a second-line therapy, with resolutionrates of 83.3% to 100%. Combination therapy showed a significantly higher resolution rate than did dietarymanagement alone (97.8% vs 78.9%, P = 0.02). The time to resolution was significantly shorter with octreotidecontainingregimens than with dietary management alone (median, 7 days vs 14 days;P = 0.03).CONCLUSIONA stepwise approach to CA management is recommended, initiating dietary interventions and escalating tooctreotide when necessary. Further research through well-designed randomized controlled trials is essential toestablish standardized treatment protocols for optimizing patient outcomes.
基金supported by STI2030-Major Projects(No.2022ZD0212200)National Natural Science Foundation of China(No.62305118)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2025A1515010953)China Postdoctoral Science Foundation(No.2022M721223).
文摘The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.In this study,we employed dual-contrast functionalphotoacoustic microscopy to evaluate the impact of lipopolysaccharide-induced central nervous system inflammation on brain lymphatic function and to explore the protective effects of the P2X7 receptor(P2X7R)antagonist.Our findings demonstrated that lipopolysac-charide intervention led to impaired function of the meningeal lymphatic vessels,which was par-tially restored by the P2X7R antagonist,whereas its effects on the glymphatic system and cerebral vessels were minimal.This study further supports the feasibility of photoacoustic microscopy for assessing brain lymphatic function and highlights the therapeutic potential of P2X7R antagonism.These findings suggest that P2X7R may serve as a key target for modulating brain-lymphatic interactions,providing an experimental foundation for developing intervention strategies for neuroinflammatory and neurodegenerative diseases.
基金Supported by the Heilongjiang Provincial Health Commission Scientific Research Project,No.20230404040027the Scientific Technology Project of Qiqihar City,No.CSFGG-2025030.
文摘Mild cognitive impairment(MCI),which is a high-risk transitional phase leading to Alzheimer’s disease,is characterized by mild memory deficits and specific cognitive dysfunctions.Without effective intervention,a significant proportion of patients with MCI progress to dementia.However,current pharmacological treatments are characterized by side effects and poor patient compliance.Therefore,it is necessary to develop effective,noninvasive alternative treatments.Repetitive transcranial magnetic stimulation(rTMS)is becoming a widely studied noninvasive treatment for central nervous system disease.The therapeutic effects of rTMS on patients with MCI and its underlying mechanism are noteworthy issues.Recently,a growing number of studies have shown that meningeal lymphatic vessel damage may be related to cognitive dysfunction.Whether the improvement of the meningeal lymphatic system is an important mechanism through which rTMS improves the clinical manifestations of MCI is worthy of further study.
文摘BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicator,typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes.Contralateral axillary metastasis(CAM)without ipsilateral involvement is exceedingly rare,particularly in early-stage breast cancer.This report presents a case of CAM in a patient with triple-negative breast cancer(TNBC),underscoring diagnostic and therapeutic complexities.CASE SUMMARY A 73-year-old female presented with left-sided early-stage IDC in February 2023.Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes,a postoperative positron emission tomography(PET)scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla.Biopsy confirmed metastatic ductal carcinoma with triple-negative status,resulting in an upstaged diagnosis of metastatic breast cancer,stage IV,M1.The patient underwent six cycles of adjuvant chemotherapy,with follow-up PET imaging showing regression of the contralateral lesion.This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.CONCLUSION This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.
文摘Intestinal lymphangiectasia(IL)is characterized by the dilation of intestinal lymphatic vessels,which can rupture and cause loss of lymph into the intestine.Due to the high content of proteins,lipoproteins,and lymphocytes in the intestinal lymph,loss of lymph might result in hypoproteinemia,hypoalbuminemia,hypogammaglobulinemia,and lymphocytopenia.In addition,there may be a depletion of minerals,lipids,and fat-soluble vitamins.IL can be primary due to inherent malfunctioning of the lymphatic system,or secondly,a result of various factors that may hinder lymphatic drainage either directly or indirectly.This condition has emerged as a subject of significant clinical interest.Given that the intestinal lymphatic system plays an important role in the body’s fluid homeostasis,adaptive immunity,nutrient and drug absorption,intestinal transport,and systemic metabolism,its dysfunction may have wider implications.Although primary IL is rare,with varied clinical features,complications,treatment response,and outcomes,secondary IL is more common than previously believed.The definitive diagnosis of IL requires endoscopic demonstration of whitish villi(which frequently resemble snowflakes)and histological confirmation of dilated lacteals in the small intestinal mucosa.Treatment of IL is challenging and involves dietary modifications,managing underlying medical conditions,and using medications such as sirolimus and octreotide.Recognizing its prevalence and diverse etiology is crucial for targeted management of this challenging medical condition.This article provides a comprehensive exploration of the clinical implications associated with IL.In addition,it offers valuable insights into critical knowledge gaps in the existing diagnostic and management landscape.
基金supported by the National Key R&D Program of China(2023YFC36003200)Shanghai Mental Health Center investigator-initiated trial programme(2024-TX-001)+1 种基金Shanghai's Top Priority Research Center(2022ZZ01017)CAMS Innovation Fund for Medical Sciences(2019-12M-5-037).
文摘Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposits,accelerating the onset and progression of Alzheimer’s disease(AD).12 Given that cervical lymph nodes receive cerebrospinal fluid from the brain’s glymphatic system,34 we speculated that decompression of the lymphatic trunk and cervical lymphatic-venous anastomosis(LVA)could facilitate the flow of cerebrospinal fluid in the cranial glymphatic system,potentially accelerating the clearance of harmful beta-amyloid and tau proteins.We collaborated with surgeons who specialise in LVA supermicrosurgery for maxillofacial tumours and lymphoedema to develop a procedure to relieve the blockage of the glymphatic system.This surgery employs supermicrosurgery techniques to create LVA connecting the bilateral cervical,deep lymphatic vessels to the veins,resulting in lymphatic trunk decompression,which allows the lymph fluid in the high-pressure lymphatic vessels to flow into the low-pressure venous system.The goal of the minimally invasive surgery is to enhance the removal of proteins,such as beta-amyloid and tau,from the brain’s lymphatic systems to the maxillofacial lymphatic vessels,unclogging protein blockages within the brain.This extracranial procedure is safer than intracranial approaches.
文摘Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.
文摘BACKGROUND This study presents an evaluation of the computed tomography lymphangio-graphy(CTL)features of lymphatic plastic bronchitis(PB)and primary chylotho-rax to improve the diagnostic accuracy for these two diseases.AIM To improve the diagnosis of lymphatic PB or primary chylothorax,a retrospective analysis of the clinical features and CTL characteristics of 71 patients diagnosed with lymphatic PB or primary chylothorax was performed.METHODS The clinical and CTL data of 71 patients(20 with lymphatic PB,41 with primary chylothorax,and 10 with lymphatic PB with primary chylothorax)were collected retrospectively.CTL was performed in all patients.The clinical manifestations,CTL findings,and conventional chest CT findings of the three groups of patients were compared.The chi-square test or Fisher's exact test was used to compare the differences among the three groups.A difference was considered to be statistically significant when P<0.05.RESULTS(1)The percentages of abnormal contrast medium deposits on CTL in the three groups were as follows:Thoracic duct outlet in 14(70.0%),33(80.5%)and 8(80.0%)patients;peritracheal region in 18(90.0%),15(36.6%)and 8(80.0%)patients;pleura in 6(30.0%),33(80.5%)and 9(90.0%)patients;pericardium in 6(30.0%),6(14.6%)and 4(40.0%)patients;and hilum in 16(80.0%),11(26.8%)and 7(70.0%)patients;and(2)the abnormalities on conven-tional chest CT in the three groups were as follows:Ground-glass opacity in 19(95.0%),18(43.9%)and 8(80.0%)patients;atelectasis in 4(20.0%),26(63.4%)and 7(70.0%)patients;interlobular septal thickening in 12(60.0%),11(26.8%)and 3(30.0%)patients;bronchovascular bundle thickening in 14(70.0%),6(14.6%)and 4(40.0%)patients;localized mediastinal changes in 14(70.0%),14(34.1%),and 7(70.0%)patients;diffuse mediastinal changes in 6(30.0%),5(12.2%),and 3(30.0%)patients;cystic lesions in the axilla in 2(10.0%),6(14.6%),and 2(20.0%)patients;and cystic lesions in the chest wall in 0(0%),2(4.9%),and 2(4.9%)patients.CONCLUSION CTL is well suited to clarify the characteristics of lymphatic PB and primary chylothorax.This method is an excellent tool for diagnosing these two diseases.
基金supported by the National Natural Science Foundation of China(Grant Nos.82071199 and 81871117)the Natural Science Foundation of Jiangsu Province(Grant No.BK20230057)Shandong Postdoctoral Innovative Talents Program(Grant No.SDBX2023056).
文摘The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.
文摘In this editorial,we discuss the clinical implications of the article“Lymphatic plastic bronchitis and primary chylothorax:A study based on computed tomography lymphangiography”published by Li et al.Pulmonary lymphatic disorders involve abnormalities in the lymphatic tissues within the thoracic cavity.Specifically,pulmonary lymphatic perfusion syndrome describes a condition where the flow of lymphatic fluid in the lungs is redirected towards abnormally widened lymphatic vessels.Clinically,individuals with this syn-drome may experience symptoms such as chyloptysis,plastic bronchitis(PB),chylothorax,chylopericardium,and interstitial lung disease.These disorders can be caused by various factors,including PB,chylothorax,and complex lymphatic malformations.Advancements in lymphatic imaging techniques,such as in-tranodal lymphangiography,computed tomography lymphangiography,and dynamic contrast-enhanced magnetic resonance lymphangiography,have enabled the detection of abnormal lymphatic flow.This has enhanced our understanding of the pathophysiology of these conditions.Additionally,innovative minimally invasive treatments,such as thoracic duct embolization,selective embolization of lymphatic channels,and surgical procedures aim to improve clinical condition of patients and address their dietary needs.
基金supported by the National Natural Science Foundation of China(No.81974321)the Discipline Innovation and Talent Introduction Program to Universities from Ministry of Education of China(Project 111)+3 种基金the Tackling Project for Science and Technology of Xinxiang City(No.GG2019003)the Natural Science Foundation of Henan Province of China(No.212300410173)the State Administration of Traditional Chinese Medicine Young Qi Huang Scholar,and the Innovation Team Project of Scientific Research of Traditional Chinese Medicine of Shanghai Health Committee(No.2022CX001)China.
文摘Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely investigated.In this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of GSD.Compared to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in OCPs.In the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in vitro.Using an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo.We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like phenotypes.Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the control.Based on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.
基金funded by the National Key Research and Development Program of China (Grant No. 2022YFA1305500)the National Natural Science Foundation of China (Grant Nos. 32322023, 82173272, 81825016, and 82173230)+1 种基金the Key Areas Research and Development Program of Guangdong (Grant Nos. 2022B1515120086 and 2022A1515140175)the Science and Technology Program of Guangzhou,China (Grant No. 2023A04J2206)。
文摘Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system.
文摘Objective:The possible enhancing effect of anlotinib on programmed death receptor ligand(PD-L1)antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium,including lymphatic endothelial cells(LECs)and blood endothelial cells(BECs),were determined to identify patients who would benefit from this treatment.Methods:PD-L1 positivity in LECs,BECs,and tumor cells(TCs)was assessed using paraffin sections with multicolor immunofluorescence in an investigator’s brochure clinical trial of TQB2450(PD-L1 antibody)alone or in combination with anlotinib in patients with non-small cell lung cancer.Progression-free survival(PFS)with different levels of PD-L1 expression was compared between the two groups.Results:Among 75 patients,the median PFS(mPFS)was longer in patients who received TQB2450 with anlotinib[10 and 12 mg(161 and 194 days,respectively)]than patients receiving TQB2450 alone(61 days)[hazard ratio(HR)_(10 mg)=0.390(95%confidence interval{CI},0.201–0.756),P=0.005;HR_(12 mg)=0.397(0.208–0.756),P=0.005].The results were similar among 58 patients with high PD-L1 expression in LECs and TCs[159 and 209 vs.82 days,HR_(10 mg)=0.445(0.210–0.939),P=0.034;HR_(12 mg)=0.369(0.174–0.784),P=0.009],and 53 patients with high PD-L1 expression in BECs and TCs[161 and 209 vs.41 days,HR_(10 mg)=0.340(0.156–0.742),P=0.007;HR_(12 mg)=0.340(0.159–0.727),P=0.005].No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases.Conclusions:Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs.Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs,which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.
