鼻咽癌调强放疗致急性放射性口干的剂量学研究

目的 探讨鼻咽癌调强放疗所致急性放射性口干与放疗剂量的关系。方法 收集2013年12月至2014年7月接受调强放疗的109例鼻咽癌患者,分析患者的一般临床资料及双侧腮腺、双侧下颌下腺、双侧涎腺(双侧腮腺+双侧下颌下腺)的照射剂量等数据。在放疗结束时根据口干程度把患者分为非重度口干组(57例)和重度口干组(52例),并对两组之间的一般资料以及相关的剂量学因素进行比较分析。记录双侧腮腺接受15~50 Gy照射剂量的体积百分比,采用Logistic多因素回归法分析急性重度口干的独立预测因子,并用受试者工作特征曲线(ROC)分析其诊断界值点。结果 至放疗结束,所有入组患者重度口干的发生率为47.7%(52/109)。临床因素的分析提示年龄、黏膜炎、化疗方式均与急性重度放射性口干的发生无关。非重度口干组和重度口干组剂量学指标比较的结果显示,两组平均剂量差异均有统计学意义(t=-6.179、-6.055、-2.293,P<0.05)。Logistic回归分析显示,V₃₄是判断急性重度放射性口干的独立预测因素。V₃₄的ROC曲线表明:V₃₄=49%对重度放射性口干预测的敏感度和特异度分别为71.2%和75.4% (OR=1.231,P<0.05,95%CI:1.116~1.357)。结论 在鼻咽癌调强放疗计划中,双侧腮腺的V₃₄是重度急性放射性口干的独立预测因子,可以作为评估发生急性重度放射性口干发生风险的剂量学指标。     

腹盆腔放疗诱发肠道微生态失调与肠源性感染的实验研究

目的 探索腹盆腔放疗照射对肠道微生态的影响及其与肠源性感染的关系。方法 模拟腹盆腔放疗照射BALB/c小鼠,2.0 Gy/d,连续照射5 d/周,分别于照射3周、5周和6周后停照1周的时间点收集回肠组织及其内容物样本。用实时定量RT-PCR检测抗菌肽和促炎性因子的表达;用PCR检测细菌在小鼠体内的移位情况;用变性梯度凝胶电泳技术检测分析肠道微生态的特征。结果 腹盆腔照射诱发了肠道潘氏细胞隐窝素-1和-4表达紊乱,照射3周或照射6周后停照1周,小鼠回肠隐窝素-1和-4均呈现显著性降低(t=-7.43、-3.54、-4.72、-4.27,P<0.05);而照射5周小鼠回肠隐窝素-1和-4表达明显升高(t=6.15、5.75,P<0.05)。放疗模拟照射3和5周时小鼠肠道微生物区系多样性指数和丰富度显著降低(t=-3.49、-4.19、-3.44、-4.97,P<0.05),呈现以乳酸杆菌等益生菌减少,大肠杆菌和弗氏志贺氏菌等条件致病菌增多为特征的微生态失调。受照小鼠肠系膜淋巴结和血液中的细菌DNA阳性率明显增高。照射3和5周后回肠组织IL-1β、IL-6和TNF-α显著性高表达(t=4.85、6.16、7.71、4.60、4.86、5.97,P<0.05);照射6周后停照1周时,肠道促炎性因子的表达量有所回落,但IL-1β和TNF-α的表达量仍显著性高表达(t=3.67、5.88,P<0.05)。结论 腹盆腔放疗可诱发肠道抗菌肽表达紊乱,引起肠道微生态失调,进而导致肠源性细菌移位及感染性炎症的发生。微生态可能成为减轻放疗患者消化道不良反应的有效干预靶点。     

Fiberoptic Bronchoscopy-Assisted Endotracheal Intubation in a Patient With a Large Tracheal Tumor

In the event of a high degree of airway obstruction, endotracheal intubation can be impossible and even dangerous, because it can cause complete airway obstruction, especially in patients with high tracheal lesions. However, a smaller endotracheal tube under the guidance of a bronchoscope can be insinuated past obstructive tumor in most noncircumferential cases. Here we report a case of successful fiberoptic bronchoscopy-assisted endotracheal intubation in a patient undergoing surgical resection of a large, high tracheal tumor causing severe tracheal stenosis. A 42-year-old Chinese man presented with dyspnea, intermittent irritable cough, and sleep deprivation for one and a half years. X-rays and computed tomography scan of the chest revealed an irregular pedunculated soft tissue mass within the tracheal lumen. The mass occupied over 90% of the lumen and caused severe tracheal stenosis. Endotracheal intubation was done to perform tracheal tumor resection under general anesthesia. After several failed conventional endotracheal intubation attempts, fiberoptic bronchoscopy-assisted intubation was successful. The patient received mechanical ventilation and then underwent tumor resection and a permanent tracheostomy. This case provides evidence of the usefulness of the fiberoptic bronchoscopy-assisted intubation technique in management of an anticipated difficult airway and suggests that tracheal intubation can be performed directly in patients with a tracheal tumor who can sleep in the supine position, even if they have occasional sleep deprivation and severe tracheal obstruction as revealed by imaging techniques.Key words: Tracheal tumors, Fiberoptic bronchoscopy, Difficulty intubation, Difficult airwayPrimary tumors of the trachea, mostly malignant, are rare, accounting for fewer than 0.1% of all tumors.¹ Surgical resection is the major option that has the potential to cure all patients with benign and low-grade tumors and most patients with malignant tracheal tumors.¹ Since surgical procedure often requires the airway to be shared by the anesthetist and the surgeon, patients who undergo tracheal tumor resection often present with a considerable degree of airway obstruction, which makes anesthetic management during surgical resection challenging.² In the event of a high degree of airway obstruction, endotracheal intubation can be impossible and even dangerous because it can cause complete airway obstruction, especially in patients with high tracheal lesions.³ However, tumors are not circumferential in most cases, and a small endotracheal tube can be insinuated past a highly obstructive tumor under the guidance of bronchoscopy.³ Here we report a case of successful fiberoptic bronchoscopy-assisted endotracheal intubation in a patient undergoing surgical resection of a large, high tracheal tumor causing severe tracheal stenosis.     

CD146 as a new marker for an increased chondroprogenitor cell sub‐population in the later stages of osteoarthritis

Cartilage‐derived mesenchymal stem cells (MSCs) have been isolated with different methods. In this study lateral and medial femoral condyles were respectively collected from patients with late‐stage osteoarthritis during the total knee arthroplasty. After digestion of the cartilage tissues with type II collagenase and analysis by fluorescence‐activated cell sorting (FACS) with CD146, a chondroprogenitor cell sub‐population were isolated and purified. The expression of other MSC‐associated markers in the CD146⁺ chondroprogenitors was analyzed by flow cytometry. Multi‐lineage differentiation capacity of CD146⁺ chondroprogenitors was compared with that of unsorted chondrocytes and adipose‐derived MSCs (ADMSCs). Higher percentage of CD146⁺ chondroprogenitors isolated from the medial femoral condyles was observed than that from the lateral. CD146⁺ chondroprogenitors expressed high levels of MSC‐specific surface antigens, and showed higher chondrogenesis capacity than ADMSCs and unsorted chondrocytes in a 3D cell pellet culture model. Thus CD146 might be a new cell surface marker for cartilage progenitor cell population in the late‐stage osteoarthritis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:84–91, 2015.     

Repositioning Potential of PAK4 to Osteoclastic Bone Resorption

Drug repositioning is a rational approach for expanding the use of existing drugs or candidate drugs to treat additional disorders. Here we investigated the possibility of using the anticancer p21‐activated kinase 4 (PAK4)‐targeted inhibitor PF‐3758309 to treat osteoclast‐mediated disorders. PAK4 was highly expressed in bone marrow cells and was phosphorylated during their differentiation into osteoclasts, and osteoclast differentiation was significantly inhibited by the dominant negative form of PAK4 and by PF‐3758309. Specifically, PF‐3758309 significantly inhibited the fusion of preosteoclasts, the podosome formation, and the migration of preosteoclasts. PF‐3758309 also had in vivo antiresorptive activity in a lipopolysaccharide‐induced bone erosion model and in vitro antiosteoclastogenic activity in the differentiation of human bone marrow–derived cells and peripheral blood mononuclear cells into osteoclasts. These data demonstrate the relevance of PAK4 in osteoclast differentiation and the potential of PAK4 inhibitors for treating osteoclast‐related disorders. © 2015 American Society for Bone and Mineral Research © 2015 American Society for Bone and Mineral Research.     

The optimal therapy of calcineurin inhibitors for pregnancy in kidney transplantation

We investigated the effects of pregnancy and delivery on renal function in transplant recipients and the relationship between doses of immunosuppressants and blood drug levels during pregnancy in 75 women with 88 deliveries. Significant serum creatinine elevation (> 0.5 mg/dL) was found in eight deliveries. In the remaining 80 cases, serum creatinine was reduced by an average of 0.14 mg/dL and returned to pre‐pregnant levels after delivery. Tacrolimus was used in 28 deliveries and cyclosporine in others. Tacrolimus blood trough level declined from 5.8 ± 2.8 ng/mL 12 months before delivery to 4.2 ± 1.8 ng/mL at second trimester; therefore, drug dose was increased from 4.1 ± 1.9 mg/d at first trimester to 5.5 ± 2.5 mg/d at delivery. Similarly, cyclosporine levels were 125.1 ± 65.1 ng/mL 12 months before delivery and 75.4 ± 35.0 ng/mL at second trimester resulting in dose elevation from 183.0 ± 71.8 mg/d at first trimester to 225.4 ± 85.1 mg/d at delivery. Renal function in female kidney transplant recipients improved slightly during pregnancy and returned to pre‐pregnant level after delivery. The dose elevation of calcineurin inhibitor by approximately 20–25% should be considered during gestational period to maintain optimal blood drug level.