Tertiary lymphoid structures as unique constructions associated with the organization,education,and function of tumor-infiltrating immunocytes

Tertiary lymphoid structures(TLSs)are formations at sites with persistent inflammatory stimulation,including tumors.These ectopic lymphoid organs mainly consist of chemo-attracting B cells,T cells,and supporting dendritic cells(DCs).Mature TLSs exhibit functional organization for the optimal development and collaboration of adaptive immune response,delivering an augmented effect on the tumor microenvironment(TME).The description of the positive correlation between TLSs and tumor prognosis is reliable only under a certain condition involving the localization and maturation of TLSs.Emerging evidence suggests that underlying mechanisms of the anti-tumor effect of TLSs pave the way for novel immunotherapies.Several approaches have been developed to take advantage of intratumoral TLSs,either by combining it with therapeutic agents or by inducing the neogenesis of TLSs.

Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases

Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of neurons.ROCKs are also involved in the biological effects of immune cells and glial cells,as well as the development of neurodegenerative disorders such as Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis.Previous studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation,regulating immune imbalance,repairing the blood-brain barrier,and promoting nerve repair and myelin regeneration.Fasudil,the first ROCKs inhibitor to be used clinically,has a good therapeutic effect on neurodegenerative diseases.Fasudil increases the activity of neural stem cells and mesenchymal stem cells,thus optimizing cell therapy.This review will systematically describe,for the first time,the effects of abnormal activation of ROCKs on T cells,B cells,microglia,astrocytes,oligodendrocytes,and pericytes in neurodegenerative diseases of the central nervous system,summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases,and clarify the possible cellular and molecular mechanisms of ROCKs inhibition.This review also proposes that fasudil is a novel potential treatment,especially in combination with cell-based therapy.Findings from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.

尿端粒酶、NMP22和ImmunoCyt联合检测在膀胱癌诊断中的应用

目的评价尿端粒酶、核基质蛋白22(NMP22)和ImmunoCyt测定在膀胱癌(BTCC)早期诊断中的应用价值,寻找早期诊断膀胱癌的有效方法。方法选择60例经病理诊断明确为早期膀胱移行细胞癌和60例非膀胱肿瘤患者,分别进行尿端粒酶、ImmunoCyt、NMP22和标准尿脱落细胞学检测。结果尿端粒酶、NMP22和ImmunoCyt和尿脱落细胞学的敏感度分别为58.3%、60.0%、61.6%、26.6%;准确度分别为75.8%,78.3%,78.3%和63.3%;特异度分别为93.3%,96.6%,95.0%和100%。三者联合检测与尿端粒酶、NMP22和ImmunoCyt单独检测相比,敏感度(分别为χ2=6.53,P<0.05;χ2=5.17,P<0.05;χ2=4.54,P<0.05)和准确度(分别为χ2=4.01,P<0.05,χ2=4.38,P<0.05,χ2=4.91,P<0.05)都有所提高;尿端粒酶、NMP22和ImmunoCyt联合检测的敏感度(χ2=28.06,P<0.01)和准确度(χ2=16.2,P<0.01)均高于尿脱落细胞学,差异有统计学意义。结论尿端粒酶、NMP22和ImmunoCyt是早期诊断膀胱移行细胞癌的一种高特异性指标,三者联合检测能提高膀胱癌的早期诊断率。

STUDY ON IMMUNOCYTE OF PARANEURONS IN THE FEMALE URETHRA OF THEWILD MAMMALS

The aim of this study is to describe the presence of neuroendocrine(NE) cells (paraneurons), producing biogenic amines and/orpeptidergic hormones, in the female urethra of wild mainmals, by means of histochemical and double labeling immunofluoresent techniques. 5-Hydroxytrytamine-. chromogranin A-, cholecystokinin- and somatostatin-contain NE cells are present in the urethral epithelium of all the species studied. Paraneurons containing 5-hydrxytryptamine colocalized with chromogranin A or cholecystokinin were also found in all subjects. Such active substances are hypothesized to play a role in the contretion of the urethral musculature, emission of urogenital fluids, and inhibition of endocrine and exocrine secretions.

Advances in anti-inflammatory and immunoregulatory mechanisms of sinomenine

Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pharmacological effects,and is clinically used for various inflammatory and autoimmune diseases.However,due to complex molecular mechanisms and pathological characteristics in inflammatory and immune responses,the precise anti-inflammatory and immunological mechanisms of sinomenine are still unclear.This review summarizes the anti-inflammatory and immunoregulatory mechanisms of sinomenine during recent years in rheumatoid arthritis,respiratory system,nervous system,digestive system and organ transplant rejection.The molecular pharmacological mechanisms of sinomenine responsible for anti-inflammatory and immunosuppressive effects were in detail introduced based on 3 aspects including cytokines induction,signal pathways modulation and immune cells function regulation.Moreover,this review also raises some concerns and challenges in future sinomenine study,which will contribute to crucial theoretical and practical significance for in-depth development and utilization of sinomenine as medicinal resource.

荧光原位杂交技术在尿路上皮肿瘤诊断中的作用

荧光原位杂交（FISH）技术是一种使用荧光标记的DNA探针评估细胞基因改变的技术，其依据为癌症是一种基因缺陷性疾病．大多数癌症伴有染色体的异常改变，采用FISH技术可检测到这些异常改变。目前美国食品药品管理局（FDA）已批准的通过尿液诊断膀胱癌的技术中。包括BTA、NMP22、ImmunoCyt以及FISH等，灵敏度和特异性最高的是FISH。近来研究还发现FISH技术有助于评估表浅膀胱癌患者对卡介苗治疗的反应，另外，FISH还可用于上尿路尿路上皮癌的诊断。本文对FISH技术在尿路上皮肿瘤诊断和随访监测中的临床应用进行综述。

The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.

Indoleamine 2,3-Dioxygenase in Endometriosis

Endometriosis(EMS)is a chronic inflammatory and estrogen-dependent gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity.Although it is a benign disease,EMS is tumor-like in several aspects,which include unrestrained growth,decreased apoptosis,and aggressive invasion.EMS involves endocrine disorders and immunological factors.Indoleamine 2,3-dioxygenase(IDO)is an intracellular enzyme that catalyzes the initial and rate-limiting step of the metabolism of tryptophan.IDO is a potential candidate facilitating EMS development.Increased IDO expression in both eutopic and ectopic endometria of women with EMS is biologically important in aspects,which include regulation of endometrial stromal cell function and modulation of adjacent local immunocytes to generate a supportive microenvironment.In turn,the expression of IDO can be regulated by the complex endocrine-immune microenvironment networks in endometrial lesions.Here,we systematically review the roles of IDO in EMS to explore its pathological implications and treatment potential.

ImmunoCyt在膀胱移行细胞癌早期诊断中的应用

目的 评价ImmunoCyt检测在膀胱癌早期诊断和随访中的作用。 方法 膀胱癌患者 86例 ,其中 38例为膀胱肿瘤行经尿道膀胱肿瘤电切术后至少 3个月的随访患者 ,4 8例有肉眼 (镜下 )血尿 ,分别进行标准尿脱落细胞学和ImmunoCyt检测。 86例均行膀胱镜检查 ,对可疑组织进行活检。 结果 膀胱镜检和病理证实 2 8例为膀胱移行细胞癌。ImmunoCyt敏感性为 82 % ,与尿脱落细胞学检查 (39% )相比差异有显著性意义 (P <0 .0 5 )。两种检查方法相结合的敏感性为 89%。Im munoCyt和细胞学的特异性分别为 78%和 94 %。 结论 ImmunoCyt较细胞学对膀胱肿瘤更敏感 ,二者联合使用可在保持高特异性的前提下提高诊断的敏感性 ,早期检测膀胱肿瘤。