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
Esophageal carcinoma(EC) is a highly lethal malignancywith a poor prognosis. One of the most important prognostic factors in EC is lymph node status. Therefore, lymphadenectomy has been recognized as a key that influe...Esophageal carcinoma(EC) is a highly lethal malignancywith a poor prognosis. One of the most important prognostic factors in EC is lymph node status. Therefore, lymphadenectomy has been recognized as a key that influences the outcome of surgical treatment for EC. However, the lymphatic drainage system of the esophagus, including an abundant lymph-capillary network in the lamina propria and muscularis mucosa, is very complex with cervical, mediastinal and celiac node spreading. The extent of lymphadenectomy for EC has always been controversial because of the very complex pattern of lymph node spreading. In this article, published literature regarding lymphatic spreading was reviewed and the current lymphadenectomy trends for EC are discussed.展开更多
Lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonl...Lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonly accepted that there were no lymphatic vessels in the primary tumor. However, recent studies have demonstrated that lymphatic vessels are detectable in certain types of cancer, and more and more evidence has shown that cancer cells invade into local lymph nodes mainly via peritumoral lymphatic vessels, Moreover, activated endothelial cells may also be important, having an influence on lymphatic metastasis of cancer cells. This article, based on recent research findings, provides an in-depth discussion of the relationship between lymphangiogenesis, tumor-derived lymphatic endothelial cells and lymphatic metastasis in head and neck cancer.展开更多
BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the ...BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the prognostic significance of lymphatic and/or blood vessel invasion(LBVI)combined with the Borrmann type in advanced proximal gastric cancer(APGC).METHODS The clinicopathological and survival data of 440 patients with APGC who underwent curative surgery between 2005 and 2012 were retrospectively analyzed.RESULTS In these 440 patients,LBVI+status was associated with Borrmann typeⅣ,low histological grade,large tumor size,and advanced pT and pN status.The 5-year survival rate of LBVI+patients was significantly lower than that of LBVI– patients,although LBVI was not an independent prognostic factor in the multivariate analysis.No significant difference in the prognosis of patients with Borrmann typeⅢ/LBVI+disease and patients with Borrmann typeⅣdisease was observed.Therefore,we proposed a revised Borrmann typeⅣ(r-BorⅣ)as Borrmann typeⅢplus LBVI+,and found that r-BorⅣwas associated with poor prognosis in patients with APGC,which outweighed the prognostic significance of pT status.CONCLUSION LBVI is related to the prognosis of APGC,but is not an independent prognostic factor.LBVI status can be used to differentiate Borrmann typesⅢandⅣ,and the same approach can be used to treat r-BorⅣand Borrmann typeⅣ.展开更多
The principle of surgical treatment for gastric cancer is the radical resectioning although the suitable resecting range for different cases of gastric cancer is still being argued upon[1-9]. However, the diagnostic a...The principle of surgical treatment for gastric cancer is the radical resectioning although the suitable resecting range for different cases of gastric cancer is still being argued upon[1-9]. However, the diagnostic accuracy of early gastric cancer (EGC) without lymphatic metastasis has obviously improved with an improvement in the diagnostic technique and due to the accumulation of knowledge on the biological profiles of EG C[10-17]. The D2 lymph node excision was used as a regular operation to treat the EGC previously. But the concept for the EGC without lymphatic metastasis has gradually changed and the less invasive resections has been applied in some cases[18-20]. This study aimed at investigating the risk factors of lymphatic metastasis in EGC in order to find out the proofs for the suitable indications for less invasive operations such as endoscopic mucosal resectioning (EMR), laparoscopic and laparotomic resectioning.展开更多
AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lympha...AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis.METHODS:Immunohistochemistry was used to evaluate IGF-1 and IGF-1R expression and lymphatic vessel density(LVD)in 40 CRC specimens.The correlation between IGF-1/IGF-1R and LVD was investigated.Effects of IGF-1 on migration and invasion of CRC cells were examined using transwell chamber assays.A LoVo cell xenograft model was established to further detect the role of IGF-1 in CRC lymphangiogenesis in vivo. RESULTS:Elevated IGF-1 and IGF-1R expression in CRC tissues was correlated with lymph node metastasis(r=0.715 and 0.569,respectively,P<0.05)and tumor TNM stage(r=0.731 and 0.609,P<0.05).A higher LVD was also found in CRC tissues and was correlated with lymphatic metastasis(r=0.405,P<0.05).A positive correlation was found between LVD and IGF-1R expression(r=0.437,P<0.05).Transwell assays revealed that IGF-1 increased the migration and invasion of CRC cells.In vivo mouse studies showed that IGF-1 also increased LVD in LoVo cell xenografts.CONCLUSION:IGF-1/IGF-1R signaling induces tumorassociated lymphangiogenesis and contributes to lymphatic metastasis of CRC.展开更多
AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their lev- ...AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their lev- els and clinicopathological parameters in gastric cancer.METHODS: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.展开更多
The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tu...The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.展开更多
AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium(DSS)-induced acute colitis.METHODS: Balb/c mice were administered 4% DSS in lieu of drinking wa...AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium(DSS)-induced acute colitis.METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence(NIRF) imaging following intradermal injection of indocyanine green(ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSSadministration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin(BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest(ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSSinduced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage.CONCLUSION: The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation.展开更多
BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic can...BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C(VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.展开更多
Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological...Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological diseases have been widely explored.The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid.The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media.Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses.After ischemic stroke,impairment of these systems could lead to cerebral edema,accumulation of toxic factors,and activation of neuroinflammation,while restoration of their normal functions can improve neurological outcomes.In this review,we summarize the basic concepts of these drainage systems,including drainage routes,physiological functions,regulatory mechanisms,and detection technologies.We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke,as well as recent advances in therapeutic strategies targeting these drainage systems.These findings provide information for potential novel strategies for treatment of stroke.展开更多
Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous syste...Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].展开更多
AIM. To explore the role of the matrix metalloproteinase-9 （MMP-9） polymorphism in colorectal cancer （CRC） in a northeast Chinese population.METHODS： Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was car...AIM. To explore the role of the matrix metalloproteinase-9 （MMP-9） polymorphism in colorectal cancer （CRC） in a northeast Chinese population.METHODS： Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Multivariate logistic regression models were used to calculate adjusted odds ratios （OR） and 95% confidence intervals （95% CI）.RESULTS： The distribution of IVllVlP-9 -2562C〉T and 279 R〉Q genotype was not significantly associated with the risk of CRC. However, the risk of Ilymph node metastasis of CRC was increased in patients with the -1562T allele （OR = 2.601; 95% CI = 1.160-5.835; P = 0.022）. The frequency of MMP-9 279RR ＋ RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old （OR = 0.102, 95% CI = 0.013-0.812; P = 0.012）.CONCLUSION： Our results indicated that the MMP-9- 1562C〉T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.展开更多
AIM: In order to obtain lymphogenous metastasisassociated genes, we compared the transcriptional profiles of mouse hepatocarcinoma cell lines Hca-F with highly lymphatic metastasis potential and Hca-P with low lymphat...AIM: In order to obtain lymphogenous metastasisassociated genes, we compared the transcriptional profiles of mouse hepatocarcinoma cell lines Hca-F with highly lymphatic metastasis potential and Hca-P with low lymphatic metastasis potential.METHODS: Total RNA was isolated from Hca-F and Hca-P cells and synthesized into double-stranded cDNA. In vitro transcription double-stranded cDNA was labeled with biotin (i.e. biotin-labeled cRNA, used as the probe). The cRNA probes hybridized with Affymetrix GeneChip() MOE430A (containing 22 690 transcripts, including 14 500 known mouse genes and 4 371 ESTs) respectively and the signals were scanned by the GeneArray Scanner. The results were then analyzed by bioinformatics.RESULTS: Out of the 14 500 known genes investigated,110 (0.8%) were up regulated at least 23 fold. Among the total 4 371 ESTs, 17 ESTs (0.4%) (data were not presented) were up regulated at least 23 fold. According to the Gene Ontology and TreeView analysis, the 110genes were further classified into two groups: differential biological process profile and molecular function profile.CONCLUSION: Using high-throughput gene chip method,a large number of genes and their cellular functions about angiogenesis, cell adhesion, signal transduction, cell motility, transport, microtubule-based process, cytoskeleton organization and biogenesis, cell cycle, transcription,chaperone activity, motor activity, protein kinase activity,receptor binding and protein binding might be involved in the process of lymphatic metastasis and deserve to be used as potential candidates for further investigation.Cyclin D1, Fosl1, Hsp47, EGFR and AR, and Cav-1 are selected as the possible candidate genes of the metastatic phenotype, which need to be validated in later experiments.ESTs (data were not presented) might indicate novel genes associated with lymphatic metastasis. Validating the function of these genes is helpful to identify the key or candidate gene/pathway responsible for lymphatic metastasis, which might be used as the diagnostic markers and the therapeutic targets for lymphatic metastasis.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
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.
文摘Esophageal carcinoma(EC) is a highly lethal malignancywith a poor prognosis. One of the most important prognostic factors in EC is lymph node status. Therefore, lymphadenectomy has been recognized as a key that influences the outcome of surgical treatment for EC. However, the lymphatic drainage system of the esophagus, including an abundant lymph-capillary network in the lamina propria and muscularis mucosa, is very complex with cervical, mediastinal and celiac node spreading. The extent of lymphadenectomy for EC has always been controversial because of the very complex pattern of lymph node spreading. In this article, published literature regarding lymphatic spreading was reviewed and the current lymphadenectomy trends for EC are discussed.
文摘Lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonly accepted that there were no lymphatic vessels in the primary tumor. However, recent studies have demonstrated that lymphatic vessels are detectable in certain types of cancer, and more and more evidence has shown that cancer cells invade into local lymph nodes mainly via peritumoral lymphatic vessels, Moreover, activated endothelial cells may also be important, having an influence on lymphatic metastasis of cancer cells. This article, based on recent research findings, provides an in-depth discussion of the relationship between lymphangiogenesis, tumor-derived lymphatic endothelial cells and lymphatic metastasis in head and neck cancer.
基金Supported by the Foundation of Innovative Talents in Higher Education of Liaoning Province,No.LR2016043
文摘BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the prognostic significance of lymphatic and/or blood vessel invasion(LBVI)combined with the Borrmann type in advanced proximal gastric cancer(APGC).METHODS The clinicopathological and survival data of 440 patients with APGC who underwent curative surgery between 2005 and 2012 were retrospectively analyzed.RESULTS In these 440 patients,LBVI+status was associated with Borrmann typeⅣ,low histological grade,large tumor size,and advanced pT and pN status.The 5-year survival rate of LBVI+patients was significantly lower than that of LBVI– patients,although LBVI was not an independent prognostic factor in the multivariate analysis.No significant difference in the prognosis of patients with Borrmann typeⅢ/LBVI+disease and patients with Borrmann typeⅣdisease was observed.Therefore,we proposed a revised Borrmann typeⅣ(r-BorⅣ)as Borrmann typeⅢplus LBVI+,and found that r-BorⅣwas associated with poor prognosis in patients with APGC,which outweighed the prognostic significance of pT status.CONCLUSION LBVI is related to the prognosis of APGC,but is not an independent prognostic factor.LBVI status can be used to differentiate Borrmann typesⅢandⅣ,and the same approach can be used to treat r-BorⅣand Borrmann typeⅣ.
基金Scientific Research Foundation for Returned Overseas Chinese Scholars,Slate Education Commission(1997-832)
文摘The principle of surgical treatment for gastric cancer is the radical resectioning although the suitable resecting range for different cases of gastric cancer is still being argued upon[1-9]. However, the diagnostic accuracy of early gastric cancer (EGC) without lymphatic metastasis has obviously improved with an improvement in the diagnostic technique and due to the accumulation of knowledge on the biological profiles of EG C[10-17]. The D2 lymph node excision was used as a regular operation to treat the EGC previously. But the concept for the EGC without lymphatic metastasis has gradually changed and the less invasive resections has been applied in some cases[18-20]. This study aimed at investigating the risk factors of lymphatic metastasis in EGC in order to find out the proofs for the suitable indications for less invasive operations such as endoscopic mucosal resectioning (EMR), laparoscopic and laparotomic resectioning.
基金Supported by Technological Research Project for Public Welfare from Science and Technology Department of Zhejiang Province,No.2010C33099
文摘AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis.METHODS:Immunohistochemistry was used to evaluate IGF-1 and IGF-1R expression and lymphatic vessel density(LVD)in 40 CRC specimens.The correlation between IGF-1/IGF-1R and LVD was investigated.Effects of IGF-1 on migration and invasion of CRC cells were examined using transwell chamber assays.A LoVo cell xenograft model was established to further detect the role of IGF-1 in CRC lymphangiogenesis in vivo. RESULTS:Elevated IGF-1 and IGF-1R expression in CRC tissues was correlated with lymph node metastasis(r=0.715 and 0.569,respectively,P<0.05)and tumor TNM stage(r=0.731 and 0.609,P<0.05).A higher LVD was also found in CRC tissues and was correlated with lymphatic metastasis(r=0.405,P<0.05).A positive correlation was found between LVD and IGF-1R expression(r=0.437,P<0.05).Transwell assays revealed that IGF-1 increased the migration and invasion of CRC cells.In vivo mouse studies showed that IGF-1 also increased LVD in LoVo cell xenografts.CONCLUSION:IGF-1/IGF-1R signaling induces tumorassociated lymphangiogenesis and contributes to lymphatic metastasis of CRC.
基金Supported by TUBTAK-SBAG (Project Number 104S581)the Turkish Academy of Sciences (TUBA)
文摘AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their lev- els and clinicopathological parameters in gastric cancer.METHODS: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20110071130011)the National Science and Technology Major Project (No. 2012ZX09304004)
文摘The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.
基金Supported by(in part)A pilot/feasibility grant from NIH/National Institute of Diabetes and Digestive and Kidney DiseaseCenter Grant P30 DK56338(for Kwon S)the Schissler Foundation Fellowship for Translational Studies of Common Human Diseases(for Agollah GD)
文摘AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium(DSS)-induced acute colitis.METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence(NIRF) imaging following intradermal injection of indocyanine green(ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSSadministration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin(BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest(ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSSinduced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage.CONCLUSION: The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation.
基金supported by a grant from the National Nature Science Foundation of China(81071982)
文摘BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C(VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.
基金supported by the Natural Science Foundation of Beijing(Key Program)No.Z200025(to JHY)+1 种基金the National Natural Science Foundation of China,No.81873818(to LHQ)Supporting Platform Construction Project of Peking University Health Science Center,No.BMU2021ZC011(to JHY).
文摘Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological diseases have been widely explored.The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid.The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media.Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses.After ischemic stroke,impairment of these systems could lead to cerebral edema,accumulation of toxic factors,and activation of neuroinflammation,while restoration of their normal functions can improve neurological outcomes.In this review,we summarize the basic concepts of these drainage systems,including drainage routes,physiological functions,regulatory mechanisms,and detection technologies.We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke,as well as recent advances in therapeutic strategies targeting these drainage systems.These findings provide information for potential novel strategies for treatment of stroke.
基金the National Natural Science Foundation of China(81871852,81200935,81671867 and 81971794)the Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Returned Scholars of the Ministry of Education of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
文摘Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].
基金Program for New Century Excellent Talents in University, NCET-06-0296
文摘AIM. To explore the role of the matrix metalloproteinase-9 （MMP-9） polymorphism in colorectal cancer （CRC） in a northeast Chinese population.METHODS： Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Multivariate logistic regression models were used to calculate adjusted odds ratios （OR） and 95% confidence intervals （95% CI）.RESULTS： The distribution of IVllVlP-9 -2562C〉T and 279 R〉Q genotype was not significantly associated with the risk of CRC. However, the risk of Ilymph node metastasis of CRC was increased in patients with the -1562T allele （OR = 2.601; 95% CI = 1.160-5.835; P = 0.022）. The frequency of MMP-9 279RR ＋ RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old （OR = 0.102, 95% CI = 0.013-0.812; P = 0.012）.CONCLUSION： Our results indicated that the MMP-9- 1562C〉T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.
基金Supported by the National Natural Science Foundation of China,No. 30371583
文摘AIM: In order to obtain lymphogenous metastasisassociated genes, we compared the transcriptional profiles of mouse hepatocarcinoma cell lines Hca-F with highly lymphatic metastasis potential and Hca-P with low lymphatic metastasis potential.METHODS: Total RNA was isolated from Hca-F and Hca-P cells and synthesized into double-stranded cDNA. In vitro transcription double-stranded cDNA was labeled with biotin (i.e. biotin-labeled cRNA, used as the probe). The cRNA probes hybridized with Affymetrix GeneChip() MOE430A (containing 22 690 transcripts, including 14 500 known mouse genes and 4 371 ESTs) respectively and the signals were scanned by the GeneArray Scanner. The results were then analyzed by bioinformatics.RESULTS: Out of the 14 500 known genes investigated,110 (0.8%) were up regulated at least 23 fold. Among the total 4 371 ESTs, 17 ESTs (0.4%) (data were not presented) were up regulated at least 23 fold. According to the Gene Ontology and TreeView analysis, the 110genes were further classified into two groups: differential biological process profile and molecular function profile.CONCLUSION: Using high-throughput gene chip method,a large number of genes and their cellular functions about angiogenesis, cell adhesion, signal transduction, cell motility, transport, microtubule-based process, cytoskeleton organization and biogenesis, cell cycle, transcription,chaperone activity, motor activity, protein kinase activity,receptor binding and protein binding might be involved in the process of lymphatic metastasis and deserve to be used as potential candidates for further investigation.Cyclin D1, Fosl1, Hsp47, EGFR and AR, and Cav-1 are selected as the possible candidate genes of the metastatic phenotype, which need to be validated in later experiments.ESTs (data were not presented) might indicate novel genes associated with lymphatic metastasis. Validating the function of these genes is helpful to identify the key or candidate gene/pathway responsible for lymphatic metastasis, which might be used as the diagnostic markers and the therapeutic targets for lymphatic metastasis.
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.
