Modification at Lys24 with fatty acid generates active calcitonin gene-related peptide with much improved plasma stability

As a 37-amino acid vasoactive neuropeptide, calcitonin gene-related peptide (CGRP) is widely distributed in nervous systems. The studies and clinical applications of CGRP are limited by its peptide nature and short half-life. A series of peptide analogues of the α-form of CGRP were synthesized. Afterwards, by using in vitro metabolic and activity studies, we prepared two high affinity analogues with significantly improved plasma stability.     

Severe thrombocytopenia in pregnancy: a case series from west China

Thrombocytopenia is the second most common hematological disease during pregnancy and is mainly caused by gestational thrombocytopenia, immune thrombocytopenia, or preeclampsia/HELLP syndrome. This study aims to investigate the causes and pregnancy outcomes of thrombocytopenia in pregnancies with platelet counts below 50 × 10⁹/L. We retrospectively analyzed the pregnancies diagnosed with severe thrombocytopenia at a tertiary care center in western China between January 2009 and December 2017. All enrolled pregnancies were divided into three groups according to the lowest platelet counts: group A (30–50 × 10⁹/L), group B (10–30 × 10⁹/L), and group C (< 10 × 10⁹/L). Maternal and fetal outcomes were observed and compared among these three platelet levels. A total of 533 consecutive pregnancies were included. A relatively large proportion (37.3%, 199/533) of them showed a history of thrombocytopenia before pregnancy or during a previous pregnancy. Most of the women (70.2%, 374/533) received corticosteroids, intravenous immunoglobulin, or platelet transfusion treatments. The incidence of preterm birth < 37 weeks (26.3%, 15/57), cesarean section (93%, 53/57), and neonatal intensive care unit (NICU) admission (31.6%, 18/57) occurred significantly more often in group C than in groups A and B. Neonatal platelet counts were detected in 28.2% of the infants (155/549), and neonatal thrombocytopenia was found in 40.6% of the infants (63/155). Intracranial hemorrhage occurred in 0.9% of the neonates (5/549) throughout the study period, with neonatal nadir platelet counts between 20 × 10⁹/L and 245 × 10⁹/L. One perinatal death occurred in group C. Pregnancies with the lowest platelet counts below 10 × 10⁹/L are more often complicated by preterm birth, cesarean section, and NICU admission compared with those lowest platelet counts 30–50 × 10⁹/L and 10–30 × 10⁹/L. Neonatal intracranial hemorrhage was uncommon in pregnancies with severe thrombocytopenia. Active management should be performed to avoid possible preterm birth and neonatal NICU admission in pregnancies with the lowest platelet counts below 10 × 10⁹/L.

     

mTOR and ERK regulate VKORC1 expression in both hepatoma cells and hepatocytes which influence blood coagulation

Clinical and Experimental Medicine - Deficiency of γ-glutamyl carboxylation of coagulation factors, as evidenced by the elevated level of Des-γ-carboxyl prothrombin (DCP), is a common...     

带线锚钉在治疗肘关节“恐怖三联征”中的临床应用

目的探讨带线锚钉在手术治疗肘关节"恐怖三联征"中的临床效果。方法回顾性分析2010年1月至2017年6月期间本院手术治疗22例肘关节"恐怖三联征"患者的临床资料,根据桡骨头骨折Mason分型,Ⅰ型2例,Ⅱ型8例,Ⅲ型12例;根据尺骨冠状突骨折Regan-Morrey分型,Ⅰ型5例,Ⅱ型12例,Ⅲ型5例;22例患者均伴有内外侧副韧带损伤,并采用肘部外侧、前内侧联合入路进行手术治疗。15例患者手术后以长臂石膏托外固定1～2周,之后逐步进行肘关节被动、主动康复锻炼。7例使用可活动铰链式外固定架辅助固定的患者早期行肘关节康复锻炼。结果所有患者手术后随访6～18个月,平均12个月。末次随访时肘关节屈曲(110±10)°,伸直受限(10±4)°,前臂旋前(70±6)°,旋后(80±6)°,并对患者进行Mayo肘关节功能评分:优(≥90分)3例,良(75～89分)12例,可(60～74分)7例,优良率为68.2%。手术后2例出现异位骨化,1例出现一过性的正中神经症状,无感染、肘关节不稳定、骨折不愈合、脱位及肘关节僵硬等并发症。结论带线锚钉通过对肘关节内外侧副韧带、关节囊等软组织修复,既增加了肘关节的稳定性,同时也减少了相关并发症的发生,值得临床推广应用。     

Euxanthone Impairs the Metastatic Potential of Osteosarcoma by Reducing COX-2 Expression

Osteosarcoma (OS) is one of the most common malignancies of bone. This study was aimed to explore the anti-metastatic effect of euxanthone on OS. Adhesion assay and Transwell assay were used to examine the effect of euxanthone on adhesion, migration and invasion of OS cells. COX-2-over-expressing plasmid was applied to transfect OS cells to assess whether COX-2 affects the anti-metastatic function of euxanthone. PDCD4 knockdown and miR-21 mimic were applied to assess whether euxanthone suppresses the transactivation of c-jun via modulating miR-21-PDCD4 signaling. The effect of euxanthone in vivo was also examined by lung metastasis assay. Euxanthone, a xanthone derivative extracted from Polygala caudata, has been found to exhibit anti-neoplastic activities. In present study, our results showed that euxanthone suppressed cell adhesion, migration, and invasion in OS cells. Our experimental data also showed that repression of COX-2 by euxanthone mediated its anti-metastatic activities. Moreover, our findings revealed that euxanthone modulated the COX-2 expression through the miR-21/PDCD4/c-jun signaling pathway. The anti-metastatic activities of euxanthone were also validated in a pulmonary metastasis model. Taken together, our results highlighted the potential of euxanthone to be used in the treatment of OS. Anat Rec, 302:1399–1408, 2019. © 2018 Wiley Periodicals, Inc.     

Fine‐needle aspiration of alveolar soft part sarcoma: Histologic correlation and aberrant CD68 expression

Alveolar soft part sarcoma is a rare highly malignant neoplasm of the soft tissue and usually occurs in the lower extremities of children and young adults. We report two cases of alveolar soft part sarcoma: a 24‐year‐old Latino man with a 10‐ cm neck mass and a 56‐year‐old Latino woman with a recurring thigh mass. Fine‐needle aspiration and a core biopsy were performed on both, which was followed by tumor resection on the man. The smears displayed numerous loosely cohesive or single large cells with abundant granular cytoplasm, round nuclei, vesicular chromatin, and occasional prominent nucleoli. Periodic and Schiff (PAS)‐positive, diastase‐resistant rhomboid, or needle‐shaped crystals were present. Both tumors had diffuse and strong nuclear TFE3 expression and aberrant cytoplasmic CD68 expression. Fluorescence in situ hybridization analysis was performed in the first case, which detected a characteristic translocation t(X;17)(p11;q25). The diagnosis of alveolar soft part sarcoma was rendered in both cases. Herein, we present the cytology, histology, immunohistochemistry, and molecular findings and discuss the differential diagnosis.     

合并心内畸形动脉导管未闭的一期外科治疗

目的探讨合并心内畸形动脉导管未闭(PDA)的一期外科治疗及预防术中灌注肺的方法。方法26例患者,5例采用正中劈胸骨经心包外分离双重结扎PDA,5例外循环心脏不停跳下切开肺动脉直视缝闭PDA,16例深低温体外循环辅助心脏停跳下切开肺动脉直视缝闭PDA,同期行心内畸形矫治。结果1例出现围手术期肺灌注,无早期死亡病例,均痊愈出院,随访2个月至4年,恢复良好,无晚期死亡。结论心内畸形合并PDA应早行同期矫治,体外循环前或阻断主动脉前结扎或缝闭PDA能明显降低肺部并发症。     

Abnormal neural responses to harmonic syntactic structures in congenital amusia

In music, harmonic syntactic structures are organized hierarchically through local and long‐distance dependencies. This study investigated whether congenital amusia, a neurodevelopmental disorder of pitch perception, is associated with impaired processing of harmonic syntactic structures. For stimuli, we used harmonic sequences containing two phrases, where the first phrase ended with a half cadence and the second with an authentic cadence. In Experiment 1, we manipulated the ending chord of the authentic cadence to be either syntactically regular or irregular based on local dependencies. Sixteen amusics and 16 controls judged the expectedness of these chords while their EEG waveforms were recorded. In comparison to the regular endings, irregular endings elicited an ERAN, an N5, and a late positive component in controls but not in amusics, indicating that amusics were impaired in processing local syntactic dependencies. In Experiment 2, we manipulated the half cadence of the harmonic sequences to either adhere to or violate long‐distance syntactic dependencies. In response to irregular harmonic sequences, an ERAN‐like component and an N5 were elicited in controls but not in amusics, suggesting that amusics were impaired in processing long‐distance syntactic dependencies. Furthermore, for controls, the neural processing of local and long‐distance syntactic dependencies was correlated at the later integration stage but not at the early detection stage. These findings indicate that amusia is associated with impairment in the detection and integration of local and long‐distance syntactic violations. The implications of these findings in terms of hierarchical music‐syntactic processing are discussed.