Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

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.

Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases

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.

Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

AIM： To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. METHODS： Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power （×200） fields with the highest lymphatic vessel density （LVD）, termed ＂hot spots＂; were identified for each layer （mucosa, muscle layer, and perimuscular connective tissue）. In individual hot spots, the LVD and relative lymphatic vessel area （LVA） were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses. RESULTS： In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2, 35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively. Thus, both the LVD and LVA differed significantly （P 〈 0.001 and P 〈 0.001, respectively; KruskaI-Wallis test） among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most （98 of 108） of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer. CONCLUSION： The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 （tumor invading the perimuscular connective tissue） or more advanced gallbladder carcinoma.

A Meta-Analysis of Lymphatic Vessel Invasion Correlated with Pathologic Factors in Invasive Breast Cancer

Objectives: The invasive breast cancer is divided into four clinical subtypes: Luminal A-like, Luminal B-like, HER-2 positive, and triple-negative according to the expression status of estrogen receptor (ER), progesterone receptor(PR), human epidermal growth factor receptor-2 (HER-2) and Ki-67. The prognosis and treatment strategy vary with subtypes. The current studies have reported the relation between lymphatic vessel invasion (LVI) and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer, but the results were debatable. So the meta-analysis was conducted to confirm the relation between LVI and the four factors. Methods: Literature was searched by entering the terms: breast AND (neoplasm OR cancer OR carcinoma) AND (lymphovascular OR “lymph vessel” OR “lymphatic vessel” invasion OR carcinoma embolus) AND (ER OR estrogen receptor OR PR OR progesterone receptor OR HER-2 OR human epidermal growth factor receptor-2 OR Ki-67 OR clinicopathological) in Pubmed. The merged odds ratio (OR) and 95% confidence interval (CI) were estimated using fixed-effect model. Review Manager 5.2 was used to analysis the relation between LVI and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer respectively. The fail-safe number was used to estimate publication bias. Results: The analysis included 5 studies, LVI positive rate was significant lower in ER positive, PR positive, HER-2 negative, low Ki-67 expression group statistically. The OR and 95% CI were 0.6(0.44 - 0.81), 0.64(0.43 - 0.95), 1.52(1.03 - 2.24), 5.29(1.53 - 18.35) respectively.Conclusions:?LVI was significantly correlated with the expression status of ER, PR, HER-2 and Ki-67 in invasive breast cancer. Furthermore, LVI was consistent with poor prognostic expression status of the four factors.

Detection of D2-40 monoclonal antibody-labeled lymphatic vessel invasion in esophageal squamous cell carcinoma and its clinicopathologic significance

Objective： This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion （LVI） labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma （ESCC）. Methods： Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. Results： The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis （P〈0.001）. The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Mthough univariate regression analysis showed significant difference between the two groups （P=0.014）, multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients （P=0.062）. Lymphatic node metastasis （P=0.031）, clinical stage （P=0.019）, and residual tumor （P=0.026） were the independent prognostic factors. Conclusion： LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.

Tumor-Associated Lymphatic and Venous Vessels in Medullary Thyroid Carcinomas

Objective: Medullary thyroid carcinomas (MTCs) invade local lymph node through lymphatic vessels and metastasize to distant organs hematogenously and account for a significant mortality. There are possibly increased lymphatic and venous vessels, through which the tumor spreads to lymph nodes and distant organs. Materials and Methods: By immunocytochemical staining for lymphatic and venous vessels, MTC lesions with adjacent normal thyroid and both normal and metastatic lymph nodes were studied for the peritumoral lymphatic and venous vessels, which were morphometrically compared with those of normal thyroid and lymph nodes. Sixteen cases of MTC cases with adjacent thyroid tissues and attached lymph nodes were immunocytochemically stained for lymphatic vessels using lymphatic vessel hyaluronan receptor (LYVE-1) and venous vessels for factor VIII (F-8). The immunostained sections of MTC lesions and metastatic lymph nodes were morphometrically compared for the number and sizes of the vessels with those of normal thyroid tissues and lymph nodes. Results: Significantly increased lymphatic vessels and markedly increased blood vessels were identified in many MTC cases at the peritumoral tissues and metastatic lymph nodes whereas a few lymphatic vessels and no venous vessels were identified in midst of MTCs. The irregular peritumoral lymphatic vessels resembled that of immature lymphatic vessels observed in papillary thyroid carcinomas and increased irregularly, entrapped venous vessels in peritumoral tissues resembled those observed in follicular thyroid carcinomas. Conclusion: The significantly increased lymphatic vessels and markedly increased venous vessels in the peritumoral thyroid tissue support a propensity of MTCs for providing an easy access of tumor cells to both lymphatic spread to the regional lymph nodes and venous spread to distant organs with further tumor spread through metastatic lymph nodes by moderately increased lymphatic and venous vessels.

Cancer-Associated Lymphatic and Venous Vessels in Colonic Carcinomas

Objective: Colonic carcinomas spread to regional lymph nodes and liver. There are cancer-associated lymphatic and venous vessels at the margin of colonic carcinomas, which facilitate spreading carcinoma through lymphatic and venous vessels. This study aimed to examine cancer-associated lymphatic and venous vessels in TNM T1 to T3 carcinomas using lymphatic vessel hyaluronan receptor for lymphatic vessels and von Willebrand factor for venous vessels by immunocytochemical staining. Materials and Methods: A total of 40 cases of moderately differentiated colonic carcinoma were studied using routinely formalin-fixed and paraffin-embedded sections. The cases consisted of 10 cases of TNM T1, 15 cases each of T2 and T3 cases. Immunocytochemical staining was performed using goat antihuman LYVE-1for lymphatic vessels and rabbit antihuman von Willebrand factor for venous vessels. Results: In TNM T1 carcinoma, increased, irregular and narrow lymphatic and venous vessels were present in the adjacent normal mucosa to the carcinoma, some of which penetrated cancerous lesion. There were no tumor emboli in lymphatic and venous vessels. In TNM T2 carcinoma, there were few lymphatic and venous vessels in midst of the carcinoma whereas numerous small lymphatic and venous vessels were present within muscle layers adjacent to the invading carcinoma. Extramural tumor embolus was present in submucosa in one case. In TNM T3 carcinoma, cancer has invaded through the muscle layers where dilated lymphatic and venous vessels were present adjacent to cancerous nests. Tumor emboli were identified in two cases by immunocytochemical staining. Conclusion: The current study showed cancer-associated lymphatic and venous vessels at the interface in TNM T1 carcinoma to dilated intramuscular lymphatic and venous vessels adjacent to invading cancerous nests in TNM T3 carcinoma, and supports cancerous cells spread via lymphatic and venous vessels through muscle layers to subserosa as supported by tumor emboli in the lymphovascular system.

Cyclic Changes of Lymphatic and Venous Vessels in Human Endometrium

Context: Cyclic changes of endometrial arteries are well established but possible cyclic changes of lymphatic and venous vessels have not been fully documented. There are no published morphological reports to support cyclic changes of endometrial lymphatic and venous vessels. Objective: Using cryosections of human endometrium, this study aimed to unveil possible cyclic changes of lymphatic and venous vessels. We previously reported cyclic changes of lymphatic vessels in human endometrium using D2-40. Design: A total of 16 cases representing menstrual, proliferative and mid and late secretary phase were studied. For Immunocytochemical staining, lymphatic vessel endothelial hyaluronan receptor 1 and von Willebr and factor were used for lymphatic and venous vessels, respectively. We used polyclonal LYVE-1 in this study, which revealed more lymphatic vessels than using D2-40. Results: Residual lymphatic and venous vessels were present in menstrual basalis. In Day 5 - 9 endometrium, there were sparse lymphatic vessels but were numerous growing venous vessels in thin proliferating functionalis. In Day 14 - 22 endometrium, there were scattered lymphatic vessels and numerous venous vessels in functionalis. In Day 25 - 26 endometrium, there were many dilated lymphatic vessels and numerous dilated, disintegrating venous vessels in upper functionalis than lower functionalis. Conclusion: The above findings support that lymphatic vessels are sparse but venous vessels are numerous in early proliferative functionalis. Lymphatic vessels grow from basalis to thin functionalis. In premenstrual phase, lymphatic vessels proliferate from lower to upper functionalis, and both lymphatic and venous vessels disintegrate for shedding by this immunocytochemical study using lymphatic and venous markers. Thus, all lymphatic, venous and arterial vessels undergo menstrual cyclic changes and shed for menstruation.

Cyclic Changes of Lymphatic Vessels in Human Endometrium

Objective: The presence of lymphatic vessels in endometrium has been controversial and recent immunocytochemical studies with routinely paraffin embedded sections revealed lymphatic vessels in basalis and occasionally in functionalis. We aimed to investigate endometrial lymphatic vessels by immunocytochemical staining using cryosections, which provided better and consistent immunostaining for lymphatic vessels with a lymphatic marker, D2-40. We aimed further to explore the structure-function relationship of lymphatic vessels in the menstrual cycle. Materials and Methods: Sixteen cases of endometrium from menstrual, early-proliferative to latesecretary phase were immunostained for D2-40 and lymphatic vessels were morphometrically analyzed for functionalis, basalis and myometrium, respectively. Results: Lymphatic vessels were consistently most numerous in myometrium, followed by basalis in all phases whereas menstrual endometrium showed small, fragmented aggregates of lymphatic vessels in thin basalis. Earlyto mid-secretary endometrium revealed many lymphatic vessels in basalis and lower-functionalis with few lymphatic vessels in upper-functionalis. Late-secretary endometrium revealed more lymphatic vessels in upper-functionalis with dilated walls, which then burst at the surface of functionalis. Conclusions: These degenerating lymphatic vessels with markedly dilated lumen in upper-functionalis may contribute to lymphatic leakage in late-secretary phase. These immunostained lymphatic vessels in functionalis support proliferating and degenerating lymphatic vessel cycle synchronized with the menstrual cycle of endometrial arteries to maintain adequate fluid leakage.

The lymphatic drainage systems in the brain:a novel target for ischemic stroke?

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.

The lymphatic system:a therapeutic target for central nervous system disorders

The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology.They emerge as major pathways for fluid exchange.The abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in neuroimmunity.The lymphatic system,through its role in the clearance of neurotoxic proteins,autoimmune cell infiltration,and the transmission of pro-inflammatory signals,participates in the pathogenesis of a variety of neurological disorders,including neurodegenerative and neuroinflammatory diseases and traumatic injury.Vascular endothelial growth factor C is the master regulator of lymphangiogenesis,a process that is critical for the maintenance of central nervous system homeostasis.In this review,we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.

Retrospective evaluation of lymphatic and blood vessel invasion and Borrmann types in advanced proximal gastric cancer

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.

Pathological Changes of Small Blood Vessels in Maxillofacial Region Following High Velocity Missile Wound:an Experimental Study in Dogs

In order to provide an experimental foundation and pathological base for earlyreconstruction of maxillofacial tissues defects after firearms wound using microsurgicalmethods,an experiment,was made to study the microvascular pathological changesthrough light and electron microscopy observation.In the experiment we found somepathological changes of small vessels in wounded region,such as mierothrombi forma-tion,endothelial loss,internal elastic membrane break and some degenerations,necrosis within endothelial and smooth muscle cells of vessel.The nearer the woundededge was,the more evident injury was.The microvascular injurous range was 3 cm dis-tant from wounded edge,which recovered in 7 days later after wounding.The experi-ment indicated that if we used the vascularized free tissue transfer to repair defects ofmaxillofacial firearms wounds,the pedicles of flap should be anastomosed to distant re-cipient vesseles which could be chosen beyond 3 cm from wounded edge.Thereconstructive operation should be done 7 days later after wound.

Latanoprost eye drops induce conjunctival lymphatic vessel development

AIM:To investigate the effect of latanoprost eye drops on the conjunctival lymphatics.METHODS:Twenty-four healthy New Zealand White rabbits weighing 1.5 to 2.0 kg were randomly divided into three groups:latanoprost group(n=8)administered with latanoprost eye drops once a day for 2 mo,carteolol group(n=8)administered with carteolol eye drops once a day for 2 mo,and control group(n=8)without any treatment.The conjunctival tissues in the three groups were extracted to investigate the expression levels of 5’-nucleotidase(5’-Nase)by Western blot,reverse transcription-polymerase chain reaction(RT-PCR),and immunofluorescence staining,respectively.RESULTS:The protein expression level of 5’-Nase was significantly higher in latanoprost group than carteolol group(F=231.175,P<0.001)and control group(P<0.001),while there was no significant difference between the carteolol group and the control group(P>0.05).The m RNA expression level of 5’-Nase in the latanoprost group was also significantly higher than carteolol group(F=71.169 P<0.005)and control group(P<0.005).The conjunctival lymphatics were positive immunofluorescence stained with the 5’-Nase antibodies in the latanoprost group and not stained in the control group.CONCLUSION:Latanoprost eye drops can induce conjunctival lymphangiogenesis which may be concerned in clinical implications.

Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer

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.

Morphological analysis of lymph vessels and capillaries in gastric carcinoma

AIM To investigate the morphology of lymph vessels and capillaries in human gastric carcinoma and their peritumoral tissues and its relations with lymphous metastasis. METHODS The morphology and the fine distribution of lymph vessels and capillaries in and around the primary foci of gastric carcinoma were studied by 5′ Nase Alpase double staining method, the total amount, the opened amount and the opened rate of lymph vessels and capillaries were counted under light microscope (100×), and the maximal lumen area, perimeter and diameter were measured with image analysis technique. RESULTS Under light microscope, lymph vessels and capilla_ ries showed strong 5′ Nase positive reaction with brown and dark brown staining, while blood vessels and capillaries revealed significant Alpase activity with blue staining. There were a lot of lymph vessels, capillaries and solid strip like tissues in gastric carcinoma. The total amount of lymphatics in metastatic group (gastric carcinoma vs peritumoral tissue) and non_metastastic group was (26 9±14 2 vs 10 4±4 0, 11 4±3 4 and 9 7±3 2, P <0 01). Their opened rates were 21 2 vs 47 5, 40 4 vs 46 0 ( P <0 01). The maximal lumen area (1502 98±1236 91 vs 5526 80±4853 42; 1918 14±2299 24 vs 3836 16±3549 16; 5526 80±4853 42 vs 3836 16±3549 16, P <0 05), the perimeter (220 33±130 25 vs 441 43±276 51; 241 79±171 13 vs 333 80±199 66; 441 43±276 51 vs 333 80±199 60, P <0 05), and the diameter (28 80±14 98 vs 59 39±28 53; 25 37±15 79 vs 46 22±20 85; 59 39±28 53 vs 46 22±20 85, P <0 05) of lymphatics in gastric carcinoma in metastatic group were lower than those in other groups. CONCLUSION There are new born lymph capillaries in gastric carcinoma. The dilation of lymph capillaries may be related to edema in peritumoral connective tissues. The lymph node metastasis of gastric carcinoma occurs through invading mature lymph capillaries in and around the primary foci of gastric carcinoma.

Is lymphatic status related to regression of inflammation in Crohn's disease?

AIM:To investigate the status of the lymphatic vessels in the small bowel affected by Crohn's disease(CD) at the moment of surgery.METHODS:During the period January 2011-June 2011,25 consecutive patients affected by CD were operated on in our Institution.During surgery,Patent Blue Ⅴ was injected subserosally and the way it spread along the subserosa of the intestinal wall,through the mesenterial layers towards the main lymphatic collectors and eventually to the lymph nodes was observed and recorded.Since some patients had been undergone strictureplasty at previous surgery,we also examined the status of intestinal lymph vessels after previous strictureplasties.The same procedure was performed in a control group of 5 patients affected by colorectal cancer.Length of lesions,caliber,maximal thickness of the diseased intestinal wall,thickness of the wall at injection site and thickness of the mesentery were evaluated at surgery.RESULTS:We observed three features after the injection of Patent Blue Ⅴ in the intestinal loops:(1) Macroscopically healthy terminal ileum of patients with CD or colon cancer showed thin lymphatic vessels linearly directed toward the mesentery;(2) In mild lesions in which the intestinal wall did not reach 8 mm of thickness,we observed short,wide and tortuous lymphatic vessels directed longitudinally along the intestinal axis toward disease-free areas and then transversally toward the mesentery;and(3) Injection in the severely affected lesions,that had a thickness of the intestinal wall over 10 mm,did not show any feature of lymphatic vessels at least on the subserosal surface.There was a correlation between the thickness of the parietal wall and the severity of the lymphatic alterations.Normal lymphatic vessels were observed at previous strictureplasties in the presence of complete regression of the inflammation.CONCLUSION:Injection of Patent Blue Ⅴ in the intestinal wall could help distinguish healthy tracts of the small bowel from those macroscopically borderline.

Variation of blood vessels in the cranial-cervical legion

The blood vessels in the head and neck have several main roots for supplying blood to the brain and returning of blood to the heart. It was well known that each artery and vein in the head and neck has its variation. The variation of the vessels some times gives rise to unexpectable findings, which are not described in the textbook. In this study we like to show the morphological variations observed at routine autopsy cases and some forensic pathological findings caused by those variations.

Notch3/DLL4信号通路对颈部淋巴水囊瘤后淋巴管发育的影响

目的:探究Notch3/DLL4信号通路对颈部淋巴水囊瘤(CH)后淋巴管成熟发育的影响。方法:选取C57BL/6小鼠和C57BL/6背景Notch3基因敲入小鼠,将两种小鼠分为正常组(对照组)和Notch3基因敲入组(突变组)。选取F2代小鼠处死,取小鼠颈部淋巴结分别进行HE染色、Masson染色、RT-qPCR、Western blot、免疫组化检测。结果:HE及Masson染色结果显示,与对照组比,突变组小鼠的淋巴结构被显著破坏,细胞纤维化严重。RT-qPCR结果显示,与对照组比,突变组小鼠淋巴结中DLL4、Hes1和VEGFR3 mRNA表达显著下降(P<0.05)。Western blot结果显示,与对照组比,突变组小鼠淋巴结中DLL4、Hes1和VEGFR3蛋白表达显著下降(P<0.05)。免疫组化结果显示,与对照组相比,突变组小鼠淋巴结中DLL4、Hes1、Ang2、VEGFA和VEGFR3染色较浅,蛋白表达水平下降(P<0.05)。结论:Notch3/DLL4信号通路能够调控小鼠颈部CH的形成,其机制可能与淋巴管发育有关。

脑小血管病的诊治现状及未来探索之路

脑小血管病(cerebral small vessel disease,CSVD)是一组临床、影像、病理综合征,主要累及颅内小血管,起病隐匿。CSVD与卒中、认知下降、情感障碍、步态异常及尿便失禁密切相关,给家庭和社会带来沉重的疾病负担和经济负担。但CSVD的致病机制仍不明确,临床诊断标准不统一,临床诊疗和试验研究面临重大挑战。本文旨在汇总当前CSVD的可能病因、发病机制和临床诊疗研究的进展及局限性,展望CSVD未来可能的临床研究方向。