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
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 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
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
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:Lymphedema is a debilitating condition that frequently occurs after breast cancer treatment.Vas-cularized lymph node transfer(VLNT)is a promising approach to reduce lymphedema.This study used magnetic reson...Background:Lymphedema is a debilitating condition that frequently occurs after breast cancer treatment.Vas-cularized lymph node transfer(VLNT)is a promising approach to reduce lymphedema.This study used magnetic resonance lymphangiography(MRL)to assess lymphatic reconnections post-VLNT in patients with breast cancer-related lymphedema(BCRL).Methods:The clinical records of six female patients with unilateral upper limb BCRL who underwent VLNT(4 cases)or VLNT combined with breast reconstruction(2 cases)were retrospectively reviewed.All patients were examined using MRL preoperatively and at the 1-year follow-up.The morphological characteristics of the lymphatic network,dermal backflow patterns,and architecture of the lymph nodes were evaluated.Clinical outcomes,patient satisfaction,and complications were assessed.Results:At the 1-year follow-up,reduction in tissue edema and limb circumference was achieved in all six patients.In MRL,the implanted lymph nodes in the axillary region of the affected upper arm were enhanced and visualized in all six patients.Reconnected lymphatic vessels in the subcutaneous tissue associated with the implanted lymph nodes were observed in four patients.Decreased dermal backflow and lymphatic vessel dilation of the affected limbs were observed in all six patients.No disruption of the lymph flow in the donor area was detected.Conclusion:This is the first study to provide direct imaging evidence for the reconnection of afferent lymphatic channels between implanted lymph nodes and the recipient lymphatic system in patients with BCRL.Overall,our study demonstrates the mechanism and efficacy of VLNT in reducing lymphedema.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
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
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
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
BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer.In this method,the dyed lymphatic system is dissected en bloc,and sentinel nodes are identified at the back ta...BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer.In this method,the dyed lymphatic system is dissected en bloc,and sentinel nodes are identified at the back table(ex vivo).Even with lymphatic basin dissection,blood flow to the residual stomach can be preserved,and functionpreserving curative gastrectomy can be performed.The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated.We hypothesized that the oncological safety of sentinel node navigation surgery(SNNS)is not inferior to that of the guidelines.AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery.METHODS This was a retrospective cohort study.Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016.Patients from April 1999 to August 2008 were from the Department of Surgery II,Kanazawa University Hospital,and patients from August 2009 to March 2016 were from the Department of Surgical Oncology,Kanazawa Medical University Hospital.Patients who were diagnosed with gastric cancer,which was preoperatively diagnosed as superficial type(type 0),5 cm or less in length,clinical T1-2 and node negative,and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected.The overall survival(OS)and relapsefree survival(RFS)of these patients(SNNS group)were investigated.Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group.RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included.Pathological nodal metastasis was observed in 10.5%and 10.4%of the SNNS and control groups,respectively.The diagnostic abilities of sentinel node biopsy were 84%and 98.6%for sensitivity and accuracy,respectively.In the SNNS group,81.6%of patients underwent modified gastrectomy or functionpreserving curative gastrectomy with lymphatic basin dissection,in which the extent of nodal dissection was further reduced compared to the guidelines.The OS rate in the SNNS group was 96.8%at 5 years and was significantly better than 91.3%in the control group(P=0.0014).The RFS rates were equal in both groups.After propensity score matching,there were 231 patients in both groups,and the cumulative recurrence rate was 0.43%at 5 years in the SNNS group and 1.30%in the control group,which was not statistically different.CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.展开更多
AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric ...AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric cancer. METHODS： SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients. RESULTS： The SVEGF-C level in gastric cancer patients （595.9 ± 201.0 ng/L） was significantly higher （P = 0.000） than controls （360.0 ± 97.4 ng/L）. Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups Ⅲ and Ⅳ （P = 0.000）. The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively （cut-off = 542.5 ng/L）. The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues （65% vs 20%; P = 0.001）. VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage （P = 0.000）. LVD was 10.7 ± 3.1/200 HP in the experimental group vs 4.9 ± 1.3/200 HP in controls （P = 0.000）; LVD in cancerous tissues with and without LNM was 12.0 ± 2.7/200 HP vs 7.6 ± 0.5/200 HP, respectively （P = 0.000）. SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients （P = 0.000）; SVEGF-C level was related to LVD （P = 0.000）. Kaplan-Meier survival analysis factors predicating poor prognosis were： SVEGF-C level （P = 0.001）, VEGF-C expression and LVD （both P = 0.000）. CONCLUSION： SVEGF-C level, VEGF-C and LVD are related to LNI and poor prognosis of patients with gastric cancer, SVEGF-C may be a biomarker for LNI in gastric cancer,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
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
BACKGROUND Pigmented villonodular synovitis(PVNS)is a benign proliferative disorder that affects the synovial joints,bursae,and tendon sheaths.To date,few studies have reported on the treatment of postoperative pain a...BACKGROUND Pigmented villonodular synovitis(PVNS)is a benign proliferative disorder that affects the synovial joints,bursae,and tendon sheaths.To date,few studies have reported on the treatment of postoperative pain and edema in patients with PVNS.Herein,we present the case of a woman who developed pain and edema in the left lower limb 1 wk after synovectomy and arthroscopic partial meniscectomy and was unable to walk due to limited flexion and extension of the left knee.CASE SUMMARY A 32-year-old woman underwent synovectomy and arthroscopic partial meniscectomy successively and was treated with a combination of manual lymphatic drainage(MLD)and kinesio taping(KT)in our hospital to alleviate postoperative pain and edema.The following parameters were assessed at 2 wk post-treatment and 1 wk post-discharge follow up:suprapatellar circumference,infrapatellar circumference,visual analog scale score,knee range of motion,pittsburgh sleep quality index score,hamilton anxiety rating scale(HAMA)score,and hamilton depression rating scale(HAMD)score.After treatment,the postoperative pain and edema in the patient’s left knee were effectively relieved,resulting in improved sleep quality and remarkably attenuated HAMA and HAMD scores.CONCLUSION Combined MLD and KT may be an effective approach for relieving postoperative pain and edema in patients with PVNS.展开更多
The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for sol...The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.展开更多
Objective: To identify the feasibility of the lymphatic mapping and sentinel node biopsy (SNB) in patients with breast cancer and to examine whether the characteristics of the sentinel lymph node (SLN) accurately pred...Objective: To identify the feasibility of the lymphatic mapping and sentinel node biopsy (SNB) in patients with breast cancer and to examine whether the characteristics of the sentinel lymph node (SLN) accurately predict the status of axillary node. Methods: 33 patients with breast cancer intraoperatively and postoperatively underwent a lymphatic mapping and the SNB using Patent Blue. Results: The SLNs were found in 30 of 33 patients (90.9%), the SLN accurately predicted the status of the axillary in 29 (96.7%). In one case the SLN was negative, but other axillary nodes were tumor positive. Conclusion: This study confirmed that the procedure of lymphatic mapping and SNB in the patients with breast cancer is feasibility, and that the histological characteristics of the SLN accurately predict the status of the axillary node. We believe that this technique might replace axillary lymph node dissection for breast cancer patients with negative axillae in the future.展开更多
Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediat...Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is unknown.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifyingβ-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs withβ-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate thatβ-glucan-modified MSN,with a particle size of∼100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.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 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 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.
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.
基金supported by the National Natural Science Foundation of China(grant nos.81372080 and 82302822)Shanghai Municipal Key Clinical Specialty(grant no.shslczdzk00901)Shanghai Sailing Program(grant no.21YF1424000).
文摘Background:Lymphedema is a debilitating condition that frequently occurs after breast cancer treatment.Vas-cularized lymph node transfer(VLNT)is a promising approach to reduce lymphedema.This study used magnetic resonance lymphangiography(MRL)to assess lymphatic reconnections post-VLNT in patients with breast cancer-related lymphedema(BCRL).Methods:The clinical records of six female patients with unilateral upper limb BCRL who underwent VLNT(4 cases)or VLNT combined with breast reconstruction(2 cases)were retrospectively reviewed.All patients were examined using MRL preoperatively and at the 1-year follow-up.The morphological characteristics of the lymphatic network,dermal backflow patterns,and architecture of the lymph nodes were evaluated.Clinical outcomes,patient satisfaction,and complications were assessed.Results:At the 1-year follow-up,reduction in tissue edema and limb circumference was achieved in all six patients.In MRL,the implanted lymph nodes in the axillary region of the affected upper arm were enhanced and visualized in all six patients.Reconnected lymphatic vessels in the subcutaneous tissue associated with the implanted lymph nodes were observed in four patients.Decreased dermal backflow and lymphatic vessel dilation of the affected limbs were observed in all six patients.No disruption of the lymph flow in the donor area was detected.Conclusion:This is the first study to provide direct imaging evidence for the reconnection of afferent lymphatic channels between implanted lymph nodes and the recipient lymphatic system in patients with BCRL.Overall,our study demonstrates the mechanism and efficacy of VLNT in reducing lymphedema.
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(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This study was approved by the ethics committee of Kanazawa University Hospital and Kanazawa Medical University(Trial Number R093,M288)ICG mapping was approved by the ethics committee of Kanazawa Medical University(Trial NumberM404).
文摘BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer.In this method,the dyed lymphatic system is dissected en bloc,and sentinel nodes are identified at the back table(ex vivo).Even with lymphatic basin dissection,blood flow to the residual stomach can be preserved,and functionpreserving curative gastrectomy can be performed.The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated.We hypothesized that the oncological safety of sentinel node navigation surgery(SNNS)is not inferior to that of the guidelines.AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery.METHODS This was a retrospective cohort study.Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016.Patients from April 1999 to August 2008 were from the Department of Surgery II,Kanazawa University Hospital,and patients from August 2009 to March 2016 were from the Department of Surgical Oncology,Kanazawa Medical University Hospital.Patients who were diagnosed with gastric cancer,which was preoperatively diagnosed as superficial type(type 0),5 cm or less in length,clinical T1-2 and node negative,and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected.The overall survival(OS)and relapsefree survival(RFS)of these patients(SNNS group)were investigated.Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group.RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included.Pathological nodal metastasis was observed in 10.5%and 10.4%of the SNNS and control groups,respectively.The diagnostic abilities of sentinel node biopsy were 84%and 98.6%for sensitivity and accuracy,respectively.In the SNNS group,81.6%of patients underwent modified gastrectomy or functionpreserving curative gastrectomy with lymphatic basin dissection,in which the extent of nodal dissection was further reduced compared to the guidelines.The OS rate in the SNNS group was 96.8%at 5 years and was significantly better than 91.3%in the control group(P=0.0014).The RFS rates were equal in both groups.After propensity score matching,there were 231 patients in both groups,and the cumulative recurrence rate was 0.43%at 5 years in the SNNS group and 1.30%in the control group,which was not statistically different.CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.
文摘AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric cancer. METHODS： SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients. RESULTS： The SVEGF-C level in gastric cancer patients （595.9 ± 201.0 ng/L） was significantly higher （P = 0.000） than controls （360.0 ± 97.4 ng/L）. Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups Ⅲ and Ⅳ （P = 0.000）. The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively （cut-off = 542.5 ng/L）. The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues （65% vs 20%; P = 0.001）. VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage （P = 0.000）. LVD was 10.7 ± 3.1/200 HP in the experimental group vs 4.9 ± 1.3/200 HP in controls （P = 0.000）; LVD in cancerous tissues with and without LNM was 12.0 ± 2.7/200 HP vs 7.6 ± 0.5/200 HP, respectively （P = 0.000）. SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients （P = 0.000）; SVEGF-C level was related to LVD （P = 0.000）. Kaplan-Meier survival analysis factors predicating poor prognosis were： SVEGF-C level （P = 0.001）, VEGF-C expression and LVD （both P = 0.000）. CONCLUSION： SVEGF-C level, VEGF-C and LVD are related to LNI and poor prognosis of patients with gastric cancer, SVEGF-C may be a biomarker for LNI in gastric cancer,
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.
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Shanghai Municipal Health Commission,No.20214Y0078and The Key Discipline Construction Project,No.SHXHZDXK202321.
文摘BACKGROUND Pigmented villonodular synovitis(PVNS)is a benign proliferative disorder that affects the synovial joints,bursae,and tendon sheaths.To date,few studies have reported on the treatment of postoperative pain and edema in patients with PVNS.Herein,we present the case of a woman who developed pain and edema in the left lower limb 1 wk after synovectomy and arthroscopic partial meniscectomy and was unable to walk due to limited flexion and extension of the left knee.CASE SUMMARY A 32-year-old woman underwent synovectomy and arthroscopic partial meniscectomy successively and was treated with a combination of manual lymphatic drainage(MLD)and kinesio taping(KT)in our hospital to alleviate postoperative pain and edema.The following parameters were assessed at 2 wk post-treatment and 1 wk post-discharge follow up:suprapatellar circumference,infrapatellar circumference,visual analog scale score,knee range of motion,pittsburgh sleep quality index score,hamilton anxiety rating scale(HAMA)score,and hamilton depression rating scale(HAMD)score.After treatment,the postoperative pain and edema in the patient’s left knee were effectively relieved,resulting in improved sleep quality and remarkably attenuated HAMA and HAMD scores.CONCLUSION Combined MLD and KT may be an effective approach for relieving postoperative pain and edema in patients with PVNS.
基金Supported by National Natural Science Foundation of China,No.81702923,and No.81971503Open Project of State Key Laboratory of Medical Immunology,No.NKLMI2023K03+1 种基金Shanghai Shen Kang Hospital Development Center Clinical Science and Technology Innovation Project,No.SHDC12020104Basic Medical Research Project of Naval Medical University,No.2022QN072.
文摘The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.
基金a grant from CIDA(Canadian International Development Agency).
文摘Objective: To identify the feasibility of the lymphatic mapping and sentinel node biopsy (SNB) in patients with breast cancer and to examine whether the characteristics of the sentinel lymph node (SLN) accurately predict the status of axillary node. Methods: 33 patients with breast cancer intraoperatively and postoperatively underwent a lymphatic mapping and the SNB using Patent Blue. Results: The SLNs were found in 30 of 33 patients (90.9%), the SLN accurately predicted the status of the axillary in 29 (96.7%). In one case the SLN was negative, but other axillary nodes were tumor positive. Conclusion: This study confirmed that the procedure of lymphatic mapping and SNB in the patients with breast cancer is feasibility, and that the histological characteristics of the SLN accurately predict the status of the axillary node. We believe that this technique might replace axillary lymph node dissection for breast cancer patients with negative axillae in the future.
基金supported by the Doctoral Start-up Foundation of Liaoning Province,China(Grant No.:2021-BS-127)China Medical University,China Medical University Cancer Hospital in animal experiments.
文摘Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is unknown.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifyingβ-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs withβ-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate thatβ-glucan-modified MSN,with a particle size of∼100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.
