治伤巴布剂对大鼠急性软组织损伤模型P38MAPK、AKT信号通路的影响＊

目的 观察治伤巴布剂对急性软组织损伤（acute soft tissue injury， ASTI）模型p38丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）、丝/苏氨酸蛋白激酶（AKT）信号通路的影响，探讨治伤巴布剂干预ASTI的可能作用机制。方法 将40只雄性SD大鼠按照随机数字表法分为正常对照组、模型对照组、治伤巴布剂组、p38MAPK信号通路抑制剂组、AKT信号通路抑制剂组，每组8只。除正常对照组外，其余四组均予以左侧后肢小腿ASTI造模。造模成功后，治伤巴布剂组于标记部位立即予治伤巴布剂（修剪成1.5x3cm大小）外敷，并用胶布固定；其余四组均予等剂量赋形剂（修剪成1.5×3 cm大小）外敷处理，胶布固定；持续外敷，共持续24 h。p38MAPK信号通路抑制剂组在造模前30 min予腹腔注射p38MAPK信号通路抑制剂SB203580（400 μg/kg/天）1次；AKT信号通路抑制剂组在造模前30 min予腹腔注射AKT信号通路抑制剂perifosine（20 mg/kg/天）1次。分别于0（造模前）、2h、4h、8h、12h、24h测量受伤小腿肌肉处的周长，并计算肌肉肿胀率（muscle swelling rate，MSR）。24 h药物干预结束后，采用颈椎脱臼法处死大鼠。后将左侧后肢小腿损伤中心部位进行取材，分成三份。一部分用于观察组织病理学形态变化；一部分用于逆转录聚合酶链反应（RT-PCR）检测核因子-κB（nuclear factor kappa-B，NF-κB）p65 mRNA、肿瘤坏死因子-α（TNF-α）mRNA、白细胞介素-1β（IL-1β）mRNA表达水平；剩下部分用酶联免疫吸附试验（ELISA）法检测骨骼肌组织TNF-α、IL-1β含量水平及蛋白质免疫印迹（Western-blot）法测定p38MAPK、AKT、NF-κB p65、核因子抑制蛋白α（inhibitor kappa B alpha， IκBα）表达水平。结果 与正常对照组相比，模型对照组MSR显著增加（P<0.01）；病理形态学上，骨骼肌组织可见大面积肌细胞排列紊乱，肌细胞变性坏死，间质内可见红细胞聚集及大量炎症细胞浸润；骨骼肌组织TNF-α、IL-1β含量水平显著升高（P<0.01）；磷酸化p38MAPK（p-p38）/总p38MAPK（t-p38），磷酸化-AKT（p-AKT）/总-AKT（t-AKT）明显升高（P<0.01），NF-κB p65及NF-κB p65mRNA表达水平明显升高（P<0.01）。与模型对照组相比，治伤巴布剂组MSR在治疗第8 h、12 h、24 h显著下降（P<0.01），且在治疗第24 h，其MSR较p38MAPK、AKT信号通路抑制剂组下降更明显（P<0.05）；病理学评分显著下降（P<0.01），且较p38MAPK、AKT信号通路抑制剂组下降更显著（P<0.05）；骨骼肌组织TNF-α、IL-1β含量水平明显下降（P<0.01），且较p38MAPK、AKT信号通路抑制剂组更显著（P<0.05）；p-p38/t-p38及p-AKT/t-AKT明显下降（P<0.01），NF-κB p65及NF-κB p65 mRNA表达水平显著下降（P<0.01），且较p38MAPK、AKT信号通路抑制剂组在降低NF-κB p65及NF-κB p65 mRNA相对表达值方面更显著（P<0.01）。结论 治伤巴布剂可能同时对p38MAPK、AKT信号通路产生了一定的抑制作用，引起NF-κB活性下调，NF-κB p65蛋白的表达下调，进而引起骨骼肌组织TNF-α、IL-1β炎性细胞因子含量水平下调，减轻ASTI炎症反应，从而改善ASTI。     

Intraabdominal and retroperitoneal soft-tissue sarcomas – Surgical treatment and outcomes

BackgroundIntraabdominal and retroperitoneal sarcomas (IaRS) are malignant connective tissue tumors. Surgical resection is often the only curative treatment. The primary objective was to report the mid-term outcomes following contemporary treatment protocols and identify prognostic factors.MethodsA retrospective review of consecutive patients (n = 107) with IaRS treated at single center from 2013 until 2018 was conducted. Histological diagnosis, tumor grade, perioperative complications, mortality, and long-time survival were registered and retrieved from patient records. Primary and recurrent tumors were analyzed separately.ResultsA total of 107 patients were identified. Median follow-up time was 3.5 years. Thirty-day mortality was 3.4% and 90-day mortality was 5.6% for all tumors. The major complication rate was 18%. The 5-year estimated survival for primary and recurrent tumors was 55.4% and 48.4%, respectively. Multifocal disease was evident in 32% of the patient cohort, and 58% of patients in the recurrent group. Multivariate analysis for survival revealed a hazard ratio (HR) of 3.1 (95% CI 1.68–8.41) for multifocality, HR 2.9 (95% CI 1.28–6.98) for Clavien-Dindo grade, HR 2.3 (95% CI 1.21–4.31) for tumor grades 2 or 3, and HR 1.002 (95% CI 1.001–1.004) for surgical margins.ConclusionsOur study found overall acceptable morbidity and mortality, and identified prognostic markers for overall survival. Recurrent tumors were not associated with worse survival. Multifocality is associated with a worse overall survival. The prognostic factors identified were; tumor grade, multifocality, intralesional margins and postoperative complications.     

Protection against corneal hyperosmolarity with soft-contact-lens wear

Hyperosmotic tear stimulates human corneal nerve endings, activates ocular immune response, and elicits dry-eye symptoms. A soft contact lens (SCL) covers the cornea preventing it from experiencing direct tear evaporation and the resulting blink-periodic salinity increases. For the cornea to experience hyperosmolarity due to tear evaporation, salt must transport across the SCL to the post-lens tear film (PoLTF) bathing the cornea. Consequently, limited salt transport across a SCL potentially protects the ocular surface from hyperosmotic tear. In addition, despite lens-wear discomfort sharing common sensations to dry eye, no correlation is available between measured tear hyperosmolarity and SCL-wear discomfort. Lack of documentation is likely because clinical measurements of tear osmolarity during lens wear do not interrogate the tear osmolarity of the PoLTF that actually overlays the cornea. Rather, tear osmolarity is clinically measured in the tear meniscus. For the first time, we mathematically quantify tear osmolarity in the PoLTF and show that it differs significantly from the clinically measured tear-meniscus osmolarity. We show further that aqueous-deficient dry eye and evaporative dry eye both exacerbate the hyperosmolarity of the PoLTF. Nevertheless, depending on lens salt-transport properties (i.e., diffusivity, partition coefficient, and thickness), a SCL can indeed protect against corneal hyperosmolarity by reducing PoLTF salinity to below that of the ocular surface during no-lens wear. Importantly, PoLTF osmolarity for dry-eye patients can be reduced to that of normal eyes with no-lens wear provided that the lens exhibits a low lens-salt diffusivity. Infrequent blinking increases PoLTF osmolarity consistent with lens-wear discomfort. Judicious design of SCL material salt-transport properties can ameliorate corneal hyperosmolarity. Our results confirm the importance of PoLTF osmolarity during SCL wear and indicate a possible relation between PoLTF osmolarity and contact-lens discomfort.     

Health-related quality of life after isolated limb perfusion compared to extended resection,or amputation for locally advanced extremity sarcoma: Is a limb salvage strategy worth the effort?

IntroductionThe aim of this study was to compare long-term patient reported outcomes (PROs) in patients with locally advanced extremity soft tissue sarcoma (eSTS) after isolated limb perfusion followed by resection (IR), compared to extended resection (ER), primary amputation (A) or secondary amputation after IR (IR-A).MethodsPatients were selected from the respondents of a multi-institutional cross-sectional cohort survivorship study (SURVSARC) conducted among sarcoma survivors registered in the Netherlands Cancer Registry (NCR), 2–10 years after diagnosis. Used PROs were the EORTC QLQ-C30, the Cancer worry scale (CWS), the Hospital Anxiety and Depression Scale (HADS), and the Toronto Extremity Salvage Score (TESS).ResultsWe identified 97 eSTS survivors: IR = 20, ER = 49, A = 20, IR-A = 8. While there were no differences in PROs between IR and ER, results showed better functioning and functionality in both groups versus the amputation groups. The amputation groups scored significantly lower on physical functioning (A = 62.7, IR-A = 65.7 versus IR = 78.0, ER = 82.7, p = 0.001) and role functioning (A = 67.5, IR-A = 52.8 versus IR = 79.2, ER = 80.6, p = 0.039), both EORTC QLQ-C30 scales. Also for the TESS, the scores were significantly lower for the amputation groups compared to the limb sparing groups (upper extremity p = 0.007 with A = 68.9, IR-A = 71.6 versus IR = 93.3, ER = 91.1; lower extremity p < 0.001 with A = 72.2, IR-A50.9 versus IR = 84.5 and ER = 85.5). There were no significant differences between the groups on cancer worry, anxiety and depression.ConclusionHRQoL in eSTS survivors treated with IR or ER is equal; for maintenance of physical functioning and functionality IR and ER outperform an amputation.     

Functional outcomes of soft palate free flap reconstruction following oropharyngeal cancer surgery

IntroductionThe objective of this study was to assess the impact of surgical resection and free flap reconstruction of soft palate cancer on speech, swallowing and quality of life, and to identify the factors influencing functional outcomes and quality of life.Material and methodsPatients treated with surgical resection of squamous cell carcinoma and free-flap reconstruction of the soft palate were reviewed at least 12 months after surgery. Speech was assessed using the Hirose intelligibility scoring system, nasalance scoring, GRBAS scoring and the Voice Handicap Index 30 (VHI30) questionnaire. Swallowing was assessed by fiberoptic endoscopy and the Deglutition Handicap Index (DHI). Quality of life was assessed using EORTC QLQ-C30 and QLQ-H&N35 questionnaires.Results29 patients were included. Speech outcomes were satisfactory, demonstrating normal or slightly below normal speech intelligibility in 75.9% of the patients, moderate or no rhinolalia in 72.4% of the patients and mean overall VHI30 scores indicative of slight or no handicap in 86.2% of the patients. Swallowing outcomes were satisfactory, with mean overall DHI scores indicative of slight or no handicap in 82.8% of the patients. Patient quality of life was preserved as demonstrated by mean quality of life and functioning scales scores all superior to 80%.ConclusionThe sequelae arising from surgical resection and free-flap reconstruction of soft palate cancer are tolerable, involving slight handicap in terms of speech and swallowing and relatively little impact on quality of life.     

医学影像纹理分析在软组织肿瘤中的研究进展

近年来凭借大数据及深度学习使得以纹理分析(Texture Analysis)为代表的影像组学迅猛发展。随着纹理分析方法及影像新技术的不断研发应用,近年来纹理分析被越来越多的应用于临床研究,为疾病、尤其是肿瘤的诊断、分级与疗效预测评估提供有价值的医学影像依据。本文总结了纹理分析的常用方法、流程,并对软组织肿瘤的研究现况进行调查,作一综述。     

1例直肠癌患者术后继发腹壁多处坏死性软组织感染的护理

总结1例直肠癌患者术后继发腹壁多处坏死性软组织感染的护理经验。护理要点：感染性休克的早期识别和有效控制;坏死性软组织感染的识别及护理,控制全身性感染再次发生;分阶段落实个体化镇痛,改善疼痛症状;分阶段动态落实营养支持方案;实施全程心理干预。经过122 d的精心护理,8处伤口全部愈合,患者恢复良好。     

Using advocacy to increase investment in enteric vaccine development

Catalyzing and sustaining momentum for long-term research investments can be a challenge, especially for enteric pathogens like ETEC and Shigella that are most threatening to the health of children in low-resource areas, and whose vaccines would not be for global use. The 2018 Vaccines Against Shigella and ETEC (VASE) Conference included a workshop focused on building the capacity of scientists to communicate about their own research and advocate for additional attention and funding for enteric disease and vaccines research. Workshop presenters shared best practices and examples of advocacy, communications, and messaging tactics that have been used successfully during early stages of vaccine development research for other pathogens. The presentations were followed by an interactive, hands-on training for real-life communication opportunities for scientists that could result in increased research funding, including developing resonant messaging for relevant audiences and practicing interviews.     

The diagnostic significance of repeat ultrasound-guided biopsy of musculoskeletal soft-tissue lesions with initially inconclusive biopsy results

IntroductionTo determine the diagnostic yield of repeat ultrasound (US)-guided biopsy of musculoskeletal soft-tissue lesions with initially inconclusive biopsy results, and to explore predictive factors for success of repeat biopsy.Materials and methodsThis retrospective study included 42 patients who underwent a repeat (second) US-guided biopsy session to target a musculoskeletal soft-tissue lesion because an initial US-guided biopsy session provided inconclusive results. Both biopsy sessions were performed in a tertiary referral center for soft-tissue sarcomas.ResultsThe diagnostic yield of repeat US-guided biopsy was 47.6%. Malignant nature of the lesion (P = 0.031), sharp lesion borders on US (P = 0.011), and good to very good lesion visibility on US (P = 0.017) were significantly associated with a diagnostic repeat US-guided biopsy. There was also a trend towards significance (P = 0.073) for a higher number of biopsy passes through the lesion. Other patient characteristics (age and gender), magnetic resonance imaging features (lesion homogeneity on T1-weighted, T2-weighted, and gadolinium chelate enhanced sequences, borders, enhancement pattern, depth and size), US features (lesion appearance, vascular flow, and depth), biopsy-related factors (days between initial and repeat US-guided biopsy, needle diameter, maximum length of acquired samples), and operator-related factors (same or different radiologists/pathologists for initial and repeat biopsies), were not associated with the diagnostic success of the repeat US-guided biopsy.ConclusionsRepeat US-guided biopsy of a musculoskeletal soft-tissue lesion with initially inconclusive biopsy results can be useful to establish a final diagnosis. Lesion features on US (borders and visibility) may be used to prospectively determine the utility of a repeat US-guided biopsy.