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41.
Actin cytoskeleton is crucial to support spermatogenesis in the mammalian testis. However, the molecular mechanism(s) underlying changes of actin cytoskeletal organization in response to cellular events that take place across the seminiferous epithelium (e.g., self-renewal of spermatogonial stem cells, germ cell differentiation, meosis, spermiogenesis, spermiation) at specific stages of the epithelial cycle of spermatogenesis remain largely unexplored. This, at least in part, is due to the lack of suitable study models to identify the crucial regulatory proteins and to investigate how these proteins work in concert to support actin dynamics. Much of the information on the role of actin binding proteins in the literature, namely the actin bundling proteins, actin nucleation proteins and motor proteins, are either findings based on genetic models or morphological analyses. While this information is helpful to delineate the function of these proteins to support spermatogenesis, they are not helpful to identify the regulatory signaling proteins, the signaling pathways and the cascade of events to modulate actin cytoskeleton dynamics. Recent studies based on the use of toxicant models, both in vitro and in vivo, however, have bridged this gap by identifying putative regulatory and signaling proteins of actin cytoskeleton. Herein, we summarize and critically evaluate these findings. We also provide a hypothetical model by which actin cytoskeletal dynamics in Sertoli cells are regulated, which in turn supports spermatid transport across the seminiferous epithelium, and at the blood-testis barrier (BTB) during the epithelial cycle of spermatogenesis. 相似文献
42.
背景与目的以免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)为代表的免疫治疗越来越广泛地应用于肺癌治疗。然而,对于程序性死亡受体配体1(programmed cell death-ligand 1, PD-L1)高表达,即肿瘤比例评分(tumor proportion score, TPS)≥50%的晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者,采用单纯免疫治疗还是免疫联合化疗在临床上仍存争议。本研究旨在评估PD-L1高表达的晚期NSCLC患者接受单纯免疫治疗与免疫联合化疗的疗效。方法本研究回顾性分析了49例PD-L1高表达晚期NSCLC患者的临床资料。PD-L1表达采用22C3抗体行免疫组化染色,按TPS判读PD-L1表达水平。比较不同临床特征分组患者的客观缓解率(objective response rate,ORR)和无进展生存时间(progression free survival, PFS)。结果免疫单药与免疫联合化疗组的ORR分别为47.1%(8/17)和43.8%(14/32),差异无统计学意义(P=0.825)。免疫单药与免疫联合化疗组的中位PFS分别为8.0个月和6.8个月,差异无统计学意义(P=0.502)。并对本组PD-L1高表达患者免疫治疗的预测因素进行了分析,结果显示,一线免疫治疗ORR(12/19, 63.2%)显著优于二线及以上免疫治疗(10/30, 33.3%),差异有统计学意义(P=0.041),二者间PFS无差异。年龄、性别、吸烟史、功能状态评分(performance status, PS)、病理类型、肿瘤大小、肿瘤淋巴结转移(tumor node metastasis, TNM)分期与ORR和PFS不相关。结论PD-L1高表达的晚期NSCLC患者接受免疫单药和免疫联合化疗的疗效相近。PD-L1高表达患者一线免疫治疗的ORR更佳。对此类人群的最佳治疗方案有待于前瞻性临床研究进一步探索。 相似文献
43.
《Clinical neurophysiology》2021,132(12):3104-3115
ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials. 相似文献
44.
目的比较骨填充网袋椎体成形术(Vesselplasty)与经皮椎体后凸成形术(percutaneous kyphoplasty,PKP)治疗 Kümmell 病的临床疗效。方法2015 年 1 月—2018 年 12 月收治 63 例 Kümmell 病患者,其中 28 例采用 Vesselplasty 治疗(Vesselplasty 组),35 例采用 PKP 治疗(PKP 组)。两组患者性别、年龄、病程、骨密度 T 值、骨折节段及术前疼痛视觉模拟评分(VAS)、Oswestry 功能障碍指数(ODI)、伤椎前缘高度、后凸 Cobb 角等一般资料比较,差异均无统计学意义(P>0.05),具有可比性。记录两组手术时间、术中透视时间、骨水泥注射量、骨水泥渗漏率、骨水泥弥散面积率和随访期间并发症发生情况,以及术前、术后 1 d、末次随访时 VAS 评分、ODI、伤椎前缘高度、后凸 Cobb 角。 结果两组患者均获随访,随访时间 12~36 个月,平均 24.2 个月。Vesselplasty 组手术时间、术中透视时间、骨水泥注射量、骨水泥弥散面积率均明显小于 PKP 组(P<0.05)。Vesselplasty 组骨水泥渗漏率(7.14%)明显低于 PKP 组(34.29%)(χ2=5.153,P=0.023)。两组患者术后 1 d 及末次随访时 VAS 评分、ODI、伤椎前缘高度、后凸 Cobb 角均较术前显著改善(P<0.05),术后两组间比较差异均无统计学意义(P>0.05)。随访期间两组均未见术椎再塌陷,Vesselplasty 组邻椎骨折发生率(7.14%)与 PKP 组(14.29%)比较,差异无统计学意义(χ2=0.243,P=0.622)。 结论Vesselplasty 和 PKP 治疗 Kümmell 病疗效相似,均能有效缓解患者疼痛症状,改善生活质量,部分恢复伤椎高度,矫正椎体后凸。但前者具有手术时间短、术中透视时间少、骨水泥渗漏少等优势。 相似文献
45.
Suraj Kumar Kulkarni Nagaraja Moorthy Rangaraj Ramalingam 《Echocardiography (Mount Kisco, N.Y.)》2019,36(3):598-601
Antiphospholipid antibody syndrome (APLS) is a rare disorder characterized by a hypercoagulable state. Manifestations include arterial or venous thrombosis, recurrent fetal wastage, coronary artery disease, valvular heart disease, dilated cardiomyopathy, pulmonary artery hypertension, and intracardiac thrombus. Most commonly mitral valve is affected followed by aortic and then tricuspid valve. In this report, a rare case of spontaneous aortic thrombosis with tricuspid stenosis uncomplicated by other valve lesions is presented with clinical and echocardiographic studies and computed tomographic images. 相似文献
46.
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48.
目的:探讨维生素D对多囊卵巢综合征(PCOS)患者胰岛素抵抗(IR)的影响及其机制研究.方法:选取自2013年2月~2014年2月在该院就诊的48例PCOS患者作为PCOS组,另选30例健康育龄期妇女作为对照组,测量研究者身高、体质量参数,计算体质指数(BMI),采用全自动生化分析仪葡萄糖氧化酶检测空腹血糖浓度(FBG)、化学发光法检测血清空腹胰岛素(FI)及胰岛素样生长因子-1(IGF-1)水平、ELISA方法测定血清25-(OH)D3浓度,计算稳态胰岛素评价指数(HOMA-IR)用于评价胰岛素抵抗性,量化胰岛素敏感指数(QUICKI)用于评价胰岛素敏感度,并分析FI、HOMA-IR、QUICKI及IGF-1与血清25-(OH)D3浓度的相关性.结果:PCOS组BMI及FBG与对照组相比,差异无统计学差异(P>0.05),而FI、HOMA-IR、QUICKI、25-(OH) D3及IGF-1与对照组比较,差异均有统计学差异(P<0.05);并且PCOS组FI和HOMA-IR与血清25-(OH)D3浓度呈显著负相关,差异有统计学意义(P<0.05),QUICKI和IGF-1水平与血清25-(OH)D3浓度呈显著正相关,差异有统计学意义(P<0.05).结论:PCOS患者IR可能与血清中维生素D缺乏有关,而IGF-1分泌减少又可能是导致PCOS患者维生素D缺乏的重要原因. 相似文献
49.
Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in GPR103, a gene not suggested by previous studies of APS3v, T1D, or AITD, showed genome-wide significance (p < 5 × 10−8). In addition, a locus on 1p13 containing the PTPN22 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, CD40, and CTLA-4 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between AITD and T1D. 相似文献
50.
《Mayo Clinic proceedings. Mayo Clinic》2019,94(7):1321-1329
Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase. 相似文献