血瘀证临界状态的血液流变性、微循环及血浆TXB_2、6-keto-PGF_(1α)改变的观察

本文提出“证候临界状态”的概念。证候临界状态是对于证候模糊性的一种描述,证候的模糊性与证候的典型性既有区别,又有联系。通过对“血瘀证临界状态”患者的血液流变性、甲皱微循环及血浆TXB_2、6-keto-PGF_(1α)的观察并与血瘀证忠者和健康人群比较,提示血瘀证的发生、形成是一个渐进的过程,典型的血瘀证与其临界状态是血瘀证发生过程中具有联系的两个不同阶段。研究结果支持了“证候临界状态”的论述。

67例脑血栓微循环、血液流变学观察及其与中医辩证分型的探讨

６７例脑血栓微循环、血液流变学观察及其与中医辩证分型的探讨黄玉玺，张瑜华，王飞荣，刘尊尧空军广州医院近年来，国内应用微循环、血液流变学对脑血管病的研究，正日益受到重视。为探索脑血管病多部位微循环、血液流变学变化规律及其与中医辨证分型的关系，本文对６７...

恶性肿瘤的微循环与凝血机制障碍——附60例报告

本文观察了不同种类的恶性肿瘤的甲皱、眼球、舌微循环改变以及凝血象的变化,以了解其有无微循环功能障碍表现。现将结果报道如下:材料和方法1.观察对象:为1988年～1990年我院住院病人.均经临床、实验室,B 超、X 线及病理组织检查证实.其中包括肝癌25例,胃癌10例,直肠癌4例,食道癌2例,肺癌10例,白血病5例。

Research progress on the skincare efficacy of sulfated glycosaminoglycans

With the improvement of consumers’scientific skin care consciousness,skin problems-oriented efficacy skin care and precise skin care methods have become the future development trend.Glycosaminoglycans are long,linear polysaccharides comprised of repeated disaccharide units,which are highly expressed endogenously in the skin.They are commonly present in skin cells,cell surface and extracellular matrix,with pleiotropic biological function.In addition to hyaluronic acid,the sulfated glycosaminoglycans heparin,heparan sulfate,dermatan sulfate and chondroitin sulfate play an important role in anti-wrinkle,firming,soothing,and improving microvascular circulation,but are still in the research and development stage in cosmetics.This paper summarizes the skincare mechanism of sulfated glycosaminoglycans,and demonstrates the potential of sulfated glycosaminoglycans as functional raw materials in cosmetics.

Deteriorated function of cutaneous microcirculation in chronic congestive heart failure

Background Chronic congestive heart failure is a complex condition that leads to dysfunction in the peripheral microcirculation. We have previously shown that vascular reactivity is reduced with increasing age. In this study, we examined a group of very old patients with severe chronic heart failure to test the hypothesis that vascular function is further compromised by a combination of heart failure and aging. Methods Cutaneous forearm blood flow was measured by laser Doppler flowmetry and compared among three groups： Group 1 （n = 20, mean ±SE： 85.5 ±4 years）, heart failure patients with New York Heart Association class Ⅳ （NYHA Ⅳ） and with a NT-proBNP level ≥5000 ng/L; Group 2 （n = 15, mean ±SE： 76.5 ±2 years）, heart failure patients with NYHA II and NT-proBNP ≤2000 ng/L, and Group 3 （n = 10, mean ±SE： 67.6 ±3.0 years）, healthy controls with no clinical signs of heart failure. The vasodilator response to the iontophoretic administration of acetylcholine （ACh）, acting via an endothelial mechanism, and sodium nitroprusside （SNP）, acting via a smooth muscle cell mechanism, were studied. Results All patients with heart failure had significantly reduced vascular reactivity independent of the mode of stimulation （ACh, SNP or heat） when compared to healthy controls. However, the responses did not differ between the two groups of heart failure patients. Conclusions Cutaneous vascular reactivity is reduced in heart failure patients and does not correlate with the severity of the condition or age of patients.

Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion

AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.

Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury

AIM： To investigate the effect of shenfu injection on gastrointestinal microcirculation after myocardial ischemic-reperfusion （IR） injury in rabbits and probe into the mechanism. METHODS： Forty healthy flap-eared white rabbits were randomly divided into 4 groups： IR injury control group （group Ⅰ ）, shenfu injection 5 mL/kg per h group （group Ⅱ）, shenfu injection 10 mL/kg per h group （group Ⅲ） and shenfu injection 20 mL/kg per h group （group Ⅳ）. The four groups were treated with Lactated Ringer＇s solution, shenfu injection 5, 10, and 20 mL/ kg per h were infused intravenously 30 min before experiment respectively. The values of hemodynamics [mean arterial pressure （MAP）, heart rate （HR）, gastric intramucosal partial pressure of carbon dioxide （PCO2）, blood gas analysis and pH] were measured and compared with those before myocardial ischemia, 60 min after myocardial ischemia and 60, 90, and 180 rain after reperfusion. RESULTS： The MAP, HR and gastric intramucosal pH were （70.50 ± 4.50） kPa, （165 ± 14） beats per rain, 7.032 ± 0.024 in group Ⅰ 60 min after myocardial ischemia, which were significantly decreased compared with those before myocardial ischemia （88.50 ± 9.75 kPa, 217 ± 18 beats per rain, 7.112 ± 0.035, P 〈 0.05）. The MAP, HR and gastric intramucosal pH were significantly decreased in group Ⅰ 60, 90, and 180 min after reperfusion （61.50 ± 5.25 kPa, 133 ± 31 beats per rain, 6.997 ± 0.025） compared with those before reperfusion respectively （P 〈 0.05）, whereas the values were insignificantly different in groups Ⅱ, Ⅲ or Ⅳ after reperfusion, compared with those before reperfusion, and there were no significant differences between groups Ⅱ, Ⅲ, and Ⅳ after reperfusion. CONCLUSION： Pre-infusion of shenfu injection has a protective effect on gastrointestinal microcirculation after myocardial IR injury in rabbits, in a dose independent manner.

Protective effect of heme oxygenase-1 on Wistar rats with heart failure through the inhibition of inflammation and amelioration of intestinal micro- circulation

Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 （HO-1） could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of 〈 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI： saline; MI ＋ Cobalt protoporphyrin （CoPP）： CoPP solution; and MI ＋ Tin mesoporphyrin IX dichloride （SnMP）： SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiogra- phy was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bac- terial translocation （BT） incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO- 1, carbon oxide （CO）, nitric oxide （NO）, intedeuldn （IL）-10, turnour necrosis factor-et （TNF-ct）, and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI ＋ CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-ct levels, and an elevation in ileac HO-1, CO, and interleukin-10 （[L-10） levels compared to the MI group （P 〈 0.05）. The rats that received the MI ＋ SnMP injections exhibited results inverse to the MI （P 〈 0.05） group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.

Protective effects of Fufang Ejiao Jiang against aplastic anemia assessed by network pharmacology and metabolomics strategy

Objective To elucidate the mechanisms underlying the therapeutic effects of Fufang Ejiao Jiang(复方阿胶浆,FFEJJ)on aplastic anemia(AA)using integrated network pharmacology and serum metabolomics.Methods Traditional Chinese Medicine Systems Pharmacology(TCMSP),Pubmed,integrative pharmacology-based research platform of traditional Chinese medicine(TCMIP),and Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine(BATMAN-TCM)were used to identify the constituents and putative targets of FFEJJ.Gene Cards and DisGeNET databases were used to identify AA-associated targets.We constructed a herb-component-target network and analyzed the protein-protein interaction(PPI)network.Potential mechanisms were determined using Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In addition,an AA model was established using acetylphenylhydrazine(APH)and cetylphenylhydrazine(CTX).Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)-based serum metabolomics was applied to screen potential metabolites and the related pathways associated with AA and the potential anti-anemic effects of FFEJJ.Results A total of 30 active components of FFEJJ and 24 targets were related to AA.PPI network analysis showed that VEGFA,AKT1,IL-6,CASP3,and ICAM1 were key nodes overlapping with proteins known to be related to AA.KEGG pathway enrichment analysis revealed that the presumed targets of FFEJJ were mainly associated with pathways linked to the promotion of hematopoiesis and improvement of the hematopoietic microenvironment.A total of 423 metabolite biomarkers were identified between the control and AA models,which are involved in the development of AA.In contrast,FFEJJ reversed the 79 differential metabolites altered by AA.Pathway analysis suggested that the synergistic effects of FFEJJ were mainly enriched in 24 metabolic pathways.Among them,sphingolipid metabolism,glycerophospholipid metabolism,and arachidonic acid metabolism were related to promoting hematopoiesis and improving the hematopoietic microenvironment,which partially conforms with network pharmacology.The interaction network formed by three key differential metabolites,including hydroxy-eicosatetraenoic acid(HETE),sphingosine 1-phosphate(S1 P),and lysophosphatidylcholine(lyso PC),and three predicted network targets(VEGFA,CASP3,and ICAM1)may be the potential mechanism underlying the anti-AA action of the multi-component of FFEJJ.Conclusion FFEJJ could be an alternative treatment option for AA.It acts by promoting hematopoiesis and improving the hematopoietic microenvironment.Network pharmacology-integrated metabolomics makes it possible to analyze TCMs from a systems perspective and at the molecular level.

The Effects of Chinese Medicines on Micro-circulation of Nail Folds and Blood Flow Velocity of Limbs in the Patients with Arteriosclerotic Obliteration

The effects of Chinese medicines on micro-circulation and blood flow velocity in arteries of the lower limbs were observed in 33 patients with arteriosclerotic obliteration(ASO).The results showed that the integral values of micro-circulation after treatment were obviously higher than those before treatment (P<0.05 or P<0.01).Blood flow velocity in arteries of the lower limbs determined with the color Doppler ultrasound detecting method after treatment were also obviously higher than those before treatment (P<0.05 or P<0.01).In tbis series of 33 ASO patients,the markedly effective rate was 36.36%,and the total effective rate was 63.64%.The observation indicates that the recipe prescribed according to the principle of supplementing qi and activating blood circulation can effectively improve micro-circulation in ASO patients,and accelerate blood flow in arteries of the lower limbs.

Modulation by anti-oketsu formulations in Kampo medicine of human arterial stiffness

Objective:In traditional herbal medicine(Kampo medicine in Japan),'sho'is diagnosed by the traditional assessments of clinical conditions.Among a variety of the shos,there is an'oketsu'syndrome,which is a stagnation and disturbance of microcirculation.The prompt effects of four anti-oketsu formulations in Kampo medicine on cardiovascular functions were compared in oketsu and non-oketsu persons.Methods:The arterial pulse wave from radial artery is formed by the combination with ejection and reflection pulses.An augmentation index(AI),a ration of the ejection and reflection pulses,indicates a degree of arteriosclerosis.For both seventy-six students with oketsu and thirty-seven students with non-oketsu,Kampo formulations overcoming oketsu of Tokishakuyakusan(TS,Dang-Gui-Shao-Yao-San),Kamishoyosan(KS,Jia-Wei-Xiao-Yao-San),Keisibukuryogan(KB,Gui-Zhi-Fu-Ling-Wan)and Tokakujokito(TJ,Tao-He-Cheng-Qi-Tang)were taken once,and then,the cardiovascular functions including blood pressure,heart rate,central arterial blood pressure(CBP)and AI were examined for 60 min.Results:At 40-60 min after an intake,these formulations decreased the AI almost by 6-18%(n=76),by 18.3±3.1%(P<0.01,n=15)with TJ.Simultaneously,the CBP was reduced by 9.0±1.8%(P<0.05,n=23)with KS and by 9.1±2.0%(P<0.05,n=15)with TJ.On the other hands,non-oketsu group had less or no effect by any kinds of the formulations.Conclusion:The anti-oketsu formulations can exert the ameliorative action for oketsu persons via decreasing AI and CBP.

Expression pattern of GATA-1,-2 and-3 genes in leukemic bone marrow microenvironment

Objective： The aim of the study was to investigate the expression pattern of hematopoietic transcription factor GATA-1, -2 and -3 genes in leukemic bone marrow （BM） micreenvironment [including bone marrow stremal cells （BMSCs） and BM hematopoietic cells]. Methods： Mononuclear cells were isolated from BM of patients with acute myeloid leukemia （AML）, chronic myelogenous leukemia （CML）, or acute lymphoblasUc leukemia （ALL）. Adherent cells （BMSCs） and nonadherent ceils （BM hematopoietic cells） were collected after long-term culture in vitro. The semi-quantitative expression levels of GATA genes in the BMSCs or BM hematopoietic cells from patients with leukemia were analyzed by using RT-PCR-ELISA and com- pared with normal controls. Results： The expression level of GATA-1 gene in the BMSCs from CML group was significantly lower than that of the normal controls. The expression level of GATA-3 gene in the BMSCs from ALL was higher than that of the normal controls, but that from CML was lower than the normal controls. Dominant expression of GATA-3 gene was found in the normal BM hematopoietic cells. The dominant expression of GATA-2 gene was found in the normal BMSCs and the BMSCs from CML, whereas the dominant expression of GATA-3 gene was detected in the BMSCs from AML. Conclusion： GATA-1, -2 and -3 genes might play a role in hematopoiesis regulation in leukemia, and the changes of expression pattern of GATA genes might influence the hematopoiesis in BM microenvironment and relate to the pathogenesis and development of leukemia.

Cardiopulmonary bypass induced microcirculatory injury of the small bowel in rats

AIM： To investigate microvascular injury quantitatively in the small bowel with respect to cardiopulmonary bypass （CPB） and related mechanisms. METHODS： In 10 male SD rats, normothermic CPB was established and continued with a flow rate of 100-150 mL/kg per minute for 60 min, while another 10 sham-operated animals served as controls. An approximate 10-cm loop of the terminal ileum was exteriorized for observation by means of intravital fluorescence microscopy. The small bowel microcirculatory network including arterioles, capillaries, and collecting venules was observed prior to CPB, CPB 30 min, CPB 60 min, post-CPB 60 min and post-CPB 120 rain. The intestinal capillary perfusion, microvascular permeability and leukocyte adherence were also measured. RESULTS： The systemic hemodynamics remained stable throughout the experiment in both groups. In CPB animals, significant arteriolar vasoconstriction, blood velocity reduction and functional capillary density diminution were found. As concomitances, exaggerated albumin extravasation and increased leukocyte accumulation were also noted. These changes were more pronounced and there were no signs of restitution at the end of the observation period. CONCLUSION： CPB induces significant microcirculatory injury of the small bowel in rats. The major underlying mechanisms are blood flow redistribution and generalized inflammatory response associated with CPB.

Effect of gamma irradiation on nuclear factor-kappa B in cultured bone marrow stromal cells

Objective: To explore the effect of gamma irradiation on nuclear factor-kappa B in cultured bone marrow stromal cells. Methods: Immunocytochemistry, Western blot and electrophoretic mobility shift assay (EMSA) were used. Results: The expression of NF-kB in cultured mouse bone marrow stromal cells (BM-SCs) on the level of protein was elevated after exposure to 60Co in the dosage of 8. 0 Gy with the use of im-munocytochemistry and Western blot. The activity of nuclear factor-kappa B in cultured BMSCs was significantly increased after exposure to gamma irradiation by using EMSA. The activity peak was at the 4th h after irradiation. Conclusion: Our results suggest that the activation of nuclear factor-kappa B in the BMSCs after irradiation may be involved in the protection of BMSCs against apoptosis and in the recovery of hematopoiesis after radiation.

Mechanical behavior of the erythrocyte in microvessel stenosis

The passage of red blood cells （RBCs） through capillaries is essential for human blood microcirculation. This study used a moving mesh technology that incorporated leader-follower pairs to simulate the fluid-structure and structure-structure interac- tions between the RBC and a microvessel stenosis. The numerical model consisted of plasma, cytoplasm, the erythrocyte membrane, and the microvessel stenosis. Computational results showed that the rheology of the RBC is affected by the Reynolds number of the plasma flow as well as the surface-to-volume ratio of the erythroeyte. At a constant inlet flow rate, an increased plasma viscosity will improve the transit of the RBC through the microvessel stenosis. For the above reasons, we consider that the decreased hemorheology in microvessels in a pathological state may primarily be attributed to an increase in the number of white blood cells. This leads to the aggregation of RBCs and a change in the blood flow structure. The present fundamental study of hemorheology aimed at providing theoretical guidelines for clinical hemorheology.

Effects of electroacupuncture at Chize(LU 5) versus Shangjuxu(ST 37) in rats with ulcerative colitis

Objective： To compare the effects between electroacupuncture （EA） at Chize （LU 5, the He-Sea point of the Lung Meridian） and Shangjuxu （ST 37, the lower He-Sea point of the large intestine） in rats with ulcerative colitis （UC） on the variations of mesenteric microcirculation and vasoactive intestinal peptide （VIP） in the colon, lung, and hypothalamus. The relative specificity of acupoints was also explored. Methods： A total of 28 male Wistar rats were randomized into a normal group, a model group, a Chize （LU 5） group and a Shangjuxu （ST 37） group, 7 rats in each group. The UC model was established by enema with acetic acid. Since the third day after modeling, rats in the Chize （LU 5） group and Shangjuxu （ST 37） group respectively received EA at Chize （LU 5） and Shangjuxu （ST 37）, 1S min each time for successive 7 d. The variations of mesenteric microvascular calibers and blood flow status were observed by a microcirculation microscopic tester; VIP in the colon, lung and hypothalamus was measured by radioimmunoassay. Results： Compared with the normal group, the mesenteric microvascular calibers were significantly expanded in the model group （P〈0.05）; there was no significant difference between the model group and Chize （LU 5） group （P〉0.05）; compared with the model group and Chize （LU 5） group, the calibers were obviously shrunk in Shangjuxu （ST 37） group （P〈0.05）. The four groups showed no significant inter-group differences in comparing blood flow status （P〉0.05）. The colonic VIP levels in the model group and Chize （LU 5） group were significantly higher than that in the normal group （P〈0.01, P〈0.05）; the VIP level in Shangjuxu （ST 37） group was markedly lower than that in the model group （P〈0.01）. There were no significant differences among the four groups in comparing VIP level in lung and hypothalamus （P〉0.05）. Conclusion： The effects of Chize （LU 5） and Shangjuxu （ST 37） were different in treating UC. Shangjuxu （ST 37） showed a more significant efficacy in down-regulating VIP in the colon and regulating mesenteric microcirculation, while the effects of Chize （LU 5） were not obvious.

Fetal liver： an ideal niche for hematopoietic stem cell expansion

Fetal liver （FL） is an intricate and highly vascularized hematopoietic organ, which can support the extensive expansion of hematopoietic stem cells （HSCs） without loss of stenmess, as well as of the downstream lineages of HSCs. This powerful function of FL largely benefits from the niche （or microenvironment）, which provides a residence for HSC expansion. Numerous studies have demonstrated that the FL niche consists of heterogeneous cell populations that associate with HSCs spatially and regulate HSCs functionally. At the molecular level, a complex of cell extrinsic and intrinsic signaling network within the FL niche cells maintains HSC expansion. Here, we summarize recent studies on the analysis of the FL HSCs and their niche, and specifically on the molecular regulatory network for HSC expansion. Based on these studies, we hypothesize a strategy to obtain a large number of functional HSCs via 3D reconstruction of FL organoid ex vivo for clinical treatment in the future.

Enhance anti-lung tumor efficacy of chimeric antigen receptor-T cells by ectopic expression of C-C motif chemokine receptor 6

Chimeric antigen receptor-T(CAR-T)cells have limited therapeutic efficacy against solid tumors,partially due to their limited ability to reach and invade into the neoplastic foci.By gene expression profiling interactive analysis,we identified that the C-C motif chemokine ligand(CCL)20 is highly expressed in lung and other most incidence and/or mortality cancers such as colon,rectum,stomach,and liver cancers.Forced expression of C-C motif chemokine receptor 6(CCR6),the biunique receptor of CCL20,results in robust trafficking of CAR-T cells toward CCL20-secreting tumor cells.In a lung cancer xenograft mouse model,CCR6-expressing CAR-T cells efficiently migrate to and infiltrate into solid tumors upon infusion,leading to effective tumor clearance and significantly prolonged survival of tumor-bearing mice.In addition,culturing CCR6-CAR-T cells with interleukin(IL)-7 and IL-15 further improved their anti-lung cancer activity.Our findings provide supporting evidence for the clinical development of chemokine receptorengineered CAR-T cells for solid tumor immunotherapy.