白鲜皮多糖的分离纯化及抗银屑病作用

目的:对白鲜皮粗多糖(DDP)进行分离纯化,并研究其抗银屑病作用。方法:DDP经膜分离技术截留相对分子质量小于10 k Da的组分(DDP-UF),采用DEAE-52纤维素柱分离纯化得到4种组分(DDP-UF-1,DDP-UF-2,DDP-UF-3,DDPUF-4);并通过红外光谱法,高效凝胶渗透色谱法(HPGPC),高效液相色谱法(HPLC),扫描电镜(SEM)测定其理化性质及结构特征。选用咪喹莫特乳膏诱导银屑病小鼠模型,己烯雌酚诱导雌鼠阴道上皮细胞增殖,酶联免疫吸附测定法(ELISA)检测各组小鼠血清白细胞介素(IL)-17与IL-23含量,苏木精-伊红(HE)染色法观察小鼠背部皮肤组织病理变化、阴道上皮细胞有丝分裂指数变化。结果:DDP-UF-1～4均具有多糖特征吸收峰,DDP-UF-1～4相对分子质量分别为10 948,40 148,32 222,19 943 Da;单糖组成及摩尔比分别为甘露糖-葡萄糖-半乳糖(32. 45∶11. 35∶8. 69),甘露糖-鼠李糖-葡萄糖醛酸-葡萄糖-木糖(25. 68∶23. 44∶21. 62∶18. 86∶3. 68),甘露糖-鼠李糖-葡萄糖醛酸-半乳糖醛酸-木糖-半乳糖(18. 68∶4. 61∶3. 89∶1. 65∶5. 36∶6. 21),葡萄糖醛酸-半乳糖醛酸-葡萄糖-木糖-半乳糖(11. 63∶15. 26∶5. 32∶2. 08∶3. 46);扫描电镜(SEM)显示DDP-UF-1～4形态结构为片状或海绵状结构。DDP-UF-1与DDP-UF-3可改善银屑病小鼠背部皮损状态、抑制雌鼠阴道上皮细胞有丝分裂、明显降低血清IL-17,IL-23含量(P 0. 05,P 0. 01)。结论:DDP-UF-1与DDP-UF-3均具有良好的抗银屑病作用,其作用可能与抑制IL-23/IL-17信号通路有关。     

Heterogeneity in amount of growth factors secreted by platelets in platelet-rich plasma samples from alopecia patients

Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet-rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFβ1), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de-identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non-cicatricial and cicatricial alopecia, a Shapiro-Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA-cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy.     

Von Willebrand disease: diagnosis and management

Von Willebrand Disease is a common cause of excessive bruising and bleeding in children. This short article gives advice on diagnosis and management for paediatricians. Given its prevalence and presenting symptoms, VWD should always be considered in the assessment of children suspected of non-accidental injury. Its diagnosis can be challenging, not only because of the various subtypes of the disorder but because of the considerable overlap between VWD and normal individuals. Laboratory diagnosis requires a range of quantitative and qualitative tests of the VWF protein, with targeted gene analysis increasingly used to confirm the diagnosis of type 2 and type 3 VWD. Bleeding Assessment Tools may be helpful in directed laboratory testing but are often less so in young children who have had limited haemostatic challenges. Treatment for VWD includes the use of antifibrinolytic drugs, vasopressin or VWF-containing clotting factor concentrates. Treatment is often on-demand for individual bleeding episodes but there are specific indications for the use of prophylactic treatment in children.     

Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic colitis mimicking inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76‐year‐old Japanese man presented to our hospital with a 1‐year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C‐reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.     

Absence of FGFR3–TACC3 rearrangement in hematological malignancies with numerical chromosomal alteration

FGFR–TACC, found in different tumor types, is characterized by the fusion of a member of fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to a member of the transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks of FGFR–TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3–TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended.     

HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.     

Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study

IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed.     

逐瘀止血汤加减治疗慢性子宫内膜炎气虚血瘀证的疗效观察

目的 评价逐瘀止血汤加减对慢性子宫内膜炎（CE）气虚血瘀证患者妊娠结局的影响及对免疫炎症因子的调节作用。方法 将144例患者随机按数字表法分为观察组和对照组各72例。观察组脱落、失访4例，剔除2例，完成66例；对照组脱落、失访3例，剔除5例，完成65例。两组均给予抗感染治疗14 d。对照组口服妇科千金片，6片/次，3次/d。观察组内服逐瘀止血汤加减，1剂/d。两组疗程均为3个月，并随访6个月。记录治疗前后月经经量、经期和周期变化情况；进行治疗前后宫腔镜和阴道彩色多普勒超声检查，评价子宫内膜形态、子宫内膜容受性（CP）［子宫内膜厚度、阻力指数（RI），搏动指数（PI）和血流指数（FI）］等，并进行子宫内膜病理检查；进行治疗前后气虚血瘀证评分；检测治疗前后月经血白细胞介素-1β（IL-1β），IL-6和肿瘤坏死因子-α（TNF-α）水平和外周血测T淋巴亚群（CD3⁺，CD4⁺，CD8⁺）水平；随访记录妊娠情况和流产情况。进行安全性评价。结果 治疗后观察组经量、经期、周期和月经完全正常率均高于对照组（P<0.05）；观察组子宫内膜厚度和FI均高于对照组（P<0.01），RI和PI均低于对照组（P<0.01）；观察组月经血IL-1β，IL-6和TNF-α水平均低于对照组（P<0.01）；观察组CD3⁺，CD4⁺水平和CD4⁺/ CD8⁺均高于对照组（P<0.01），CD8⁺水平低于对照组（P<0.01）；在6个月随访期间，观察组妊娠率46.97%（31/66），高于对照组的27.69%（18/65）（χ²=5.197，P<0.05）；观察组子宫内膜形态疗效总有效率为96.97%（64/66），高于对照组的86.15%（56/65）（χ²=4.981，P<0.05）；观察组子宫内膜病理组织疗效总有效率为95.45%（63/66），高于对照组的84.62%（55/65）（χ²=4.304，P<0.05）；观察组综合临床疗效总有效率为93.94%（62/66），高于对照组的81.54%（55/65）（χ²=4.696，P<0.05）；两组治疗期间均未发现与中药相关不良反应。结论 逐瘀止血汤加减治疗CE气虚血瘀证患者，可调经月经、减轻临床症状，改善宫腔镜下内膜形态，调节全身和局部的免疫炎症反应，提高了CP，从而改善了妊娠结局，有着较好的综合疗效，且安全。     

Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.