The Influence of Xylazine and Clonidine on Lung Ultrasound–Induced Pulmonary Capillary Hemorrhage in Spontaneously Hypertensive Rats

Induction of pulmonary capillary hemorrhage (PCH) by lung ultrasound (LUS) depends not only on physical exposure parameters but also on physiologic conditions and drug treatment. We studied the influence of xylazine and clonidine on LUS-induced PCH in spontaneously hypertensive and normotensive rats using diagnostic B-mode ultrasound at 7.3 MHz. Using ketamine anesthesia, rats receiving saline, xylazine, or clonidine treatment were tested with different pulse peak rarefactional pressure amplitudes in 5 min exposures. Results with xylazine or clonidine in spontaneously hypertensive rats were not significantly different at the three exposure pulse peak rarefactional pressure amplitudes, and thresholds were lower (2.2 MPa) than with saline (2.6 MPa). Variations in LUS PCH were not correlated with mean systemic blood pressure. Similar to previous findings for dexmedetomidine, the clinical drug clonidine tended to increase susceptibility to LUS PCH.     

Circ_0008039 supports breast cancer cell proliferation,migration, invasion,and glycolysis by regulating the miR‐140‐3p/SKA2 axis

Circular RNAs (circRNAs) have been shown to modulate gene expression and participate in the development of multiple malignancies. The purpose of this study was to investigate the role of circ_0008039 in breast cancer (BC). The expression of circ_0008039, miR‐140‐3p, and spindle and kinetochore‐associated protein 2 (SKA2) was detected by qRT‐PCR. Cell viability, colony formation, migration, and invasion were evaluated using methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay, colony formation assay, and transwell assay, respectively. Glucose consumption and lactate production were measured using commercial kits. Protein levels of hexokinase II (HK2) and SKA2 were determined by western blot. The interaction between miR‐140‐3p and circ_0008039 or SKA2 was verified by dual‐luciferase reporter assay. Finally, a mouse xenograft model was established to investigate the roles of circ_0008039 in BC in vivo. We found that circ_0008039 and SKA2 were upregulated in BC tissues and cells, while miR‐140‐3p was downregulated. Knockdown of circ_0008039 suppressed BC cell proliferation, migration, invasion, and glycolysis. Moreover, miR‐140‐3p could bind to circ_0008039 and its inhibition reversed the inhibitory effect of circ_0008039 interference on proliferation, migration, invasion, and glycolysis in BC cells. SKA2 was verified as a direct target of miR‐140‐3p and its overexpression partially inhibited the suppressive effect of miR‐140‐3p restoration in BC cells. Additionally, circ_0008039 positively regulated SKA2 expression by sponging miR‐140‐3p. Consistently, silencing circ_0008039 restrained tumor growth via increasing miR‐140‐3p and decreasing SKA2. In conclusion, circ_0008039 downregulation suppressed BC cell proliferation, migration, invasion, and glycolysis partially through regulating the miR‐140‐3p/SKA2 axis, providing an important theoretical basis for treatment of BC.

Abbreviations

ANOVA

analysis of variance

BC

breast cancer

circRNAs

circular RNAs

DMSO

dimethyl sulfoxide

ECAR

extracellular acidification rate

ECL

enhanced chemiluminescence

FBS

fetal bovine serum

HK2

hexokinase II

MEGM

mammary epithelial growth medium

miR‐140‐3p

microRNA‐140‐3p

MTT

methylthiazolyldiphenyl‐tetrazolium bromide

PBS

phosphate‐buffered saline

PRKAR1B

protein kinase A regulatory subunit R1‐beta

SD

standard ± deviation

SKA2

spindle and kinetochore‐associated protein 2

     

Cyclic adenosine monophosphate involvement in low-dose cyclophosphamide-reversed immune evasion in a mouse lymphoma model

Lymphoma cells mobilize many mechanisms to evade the immune system. There is substantial evidence that CD4⁺CD25⁺ regulatory T cells (Tregs) play a key role in the control of immune evasion. Tregs can transfer cyclic adenosine monophosphate (cAMP) to effector T cells, suggesting an association between Tregs'' immune-evasion role and the intracellular cAMP pathway. In this study, we used A20 B-cell lymphoma mice as aggressive tumor models to investigate the mechanism of the depletion of Tregs by low-dose cyclophosphamide (CY, 20 mg/kg). The tumor-bearing mice had longer survival times and slower tumor growth rates following treatment with CY, but its effects were temporary. Along with the depletion of Tregs by low-dose CY treatment, the expression of interleukin-2 (IL-2) in T effector cells increased, and intracellular cAMP concentrations in immune cells decreased. Our study demonstrates the ability of low-dose CY to reverse Tregs-mediated immune evasion in a mouse model. The changes in intracellular cAMP concentrations correlated with the upregulation of effector T cells and the downregulation of Tregs, indicating the close association of cAMP analogs and low-dose CY in the immune therapy of B-cell lymphoma.     

Ultrasonic Cavitation-Enabled Treatment for Therapy of Hypertrophic Cardiomyopathy: Proof of Principle

Ultrasound myocardial cavitation-enabled treatment was applied to the SS-16^BN rat model of hypertrophic cardiomyopathy for proof of the principle underlying myocardial reduction therapy. A focused ultrasound transducer was targeted using 10-MHz imaging (10 S, GE Vivid 7) to the left ventricular wall of anesthetized rats in a warmed water bath. Pulse bursts of 4-MPa peak rarefactional pressure amplitude were intermittently triggered 1:8 heartbeats during a 10-min infusion of a microbubble suspension. Methylprednisolone was given to reduce initial inflammation, and Losartan was given to reduce fibrosis in the healing tissue. At 28 d post therapy, myocardial cavitation-enabled treatment significantly reduced the targeted wall thickness by 16.2% (p?<0.01) relative to shams, with myocardial strain rate and endocardial displacement reduced by 34% and 29%, respectively, which are sufficient for therapeutic treatment. Premature electrocardiogram complexes and plasma troponin measurements were found to identify optimal and suboptimal treatment cohorts and would aid in achieving the desired impact. With clinical translation, myocardial cavitation-enabled treatment should fill the need for a new non-invasive hypertrophic cardiomyopathy therapy option.     

发酵空压站冷却装置最佳排气温度及温升的确定

简述了发酵用压缩空气制备站中冷却装置温度调节的通常做法并分析其原因;通过实例计算,指出其耗能大的不合理性;通过计算分析,得到合理的并能使能耗降低的再冷却器排气温度和空气加热的温升。     

配偶夫妻疾病沟通与肠造口患者感知社会约束的交叉滞后模型

目的 探讨SHEL事故分析法在院前急救护理安全管理中的应用效果.方法 应用SHEL事故分析法对2010年1月至2011年12月院前急救护理工作中出现的25例次护理缺陷进行分析,制定护理安全管理措施并进行针对性的管理.结果 加强护理安全管理后,2012年1～12月发生护理缺陷4例次,较管理前(25例次)显著减少(P＜0.05).结论 应用SHEL事故分析法对院前急救护理缺陷进行原因分析,针对性的制定护理安全管理措施,能明显降低护理缺陷的发生,保证护理安全.     

关节镜下经髌腱入路空心拉力螺钉复位固定治疗胫骨髁间嵴撕脱骨折*

目的探讨在关节镜下经髌腱入路,利用空心拉力螺钉复位固定胫骨髁间嵴撕脱骨折(TEFx)的安全性和有效性。方法选取2014年1月-2015年12月23例TEFx的患者,均在关节镜下经髌腱入路,用空心拉力螺钉复位固定。术前Meyers-McKeever分型:Ⅱ型8例,Ⅲ型10例,Ⅳ型5例;男17例,女6例;年龄16～53岁,平均27.8岁。术前前抽屉试验、Lachman试验均阳性。比较术前术后的视觉模拟评分(VAS)、Lysholm、Tegner和国际膝关节文献委员会(IKDC)评分评价患侧膝关节功能。结果 23例患者均得到随访,随访时间30～40个月,平均36个月。术后即刻X线片示TEFx均复位良好,术后3个月骨折均愈合。无1例感染、关节僵硬、伸直受限、复位丢失及神经血管损伤等并发症。最终随访患侧膝关节活动度均恢复正常,前抽屉试验、Lachman试验均阴性。VAS评分术前(4.8±1.2)分,最终随访为(1.2±0.8)分,术前术后比较,差异有统计学意义(t=18.72,P=0.003);Lysholm评分术前为(50.8±6.2)分,最终随访为(90.8±5.4)分,术前术后比较,差异有统计学意义(t=-42.64,P=0.000);Tegner评分术前为(4.0±1.0)分,最终随访为(5.1±1.2)分,术前术后比较,差异有统计学意义(t=-16.82,P=0.005);IKDC主观评分术前为(52.5±7.4)分,最终随访为(91.5±5.7)分,术前术后比较,差异有统计学意义(t=-40.58,P=0.000)。结论膝关节镜下经髌腱入路空心拉力螺钉内固定治疗TEFx具有微创、操作简捷、固定可靠和恢复快的优点。     

司库奇尤单抗治疗中重度斑块状银屑病的近期疗效及安全性观察

【摘要】 目的 观察司库奇尤单抗治疗中重度斑块状银屑病的近期疗效及安全性。方法 2019年6 - 11月收集就诊于河南省人民医院皮肤科的中重度斑块状银屑病患者36例，给予司库奇尤单抗单药皮下注射治疗，300 mg/次，分别于基线、第1、2、3、4周注射1次，随后每4周1次，分别于第4、8、12周时记录患者银屑病皮损面积和严重度指数（PASI），观察药物不良反应。结果 36例患者均接受至少12周的治疗。4周时，8例达PASI75，其中3例达PASI90，1例达PASI100；8周时，26例达PASI75，其中16例达PASI90，4例达PASI100；12周时，32例达PASI75，其中26例达PASI90，8例达PASI100。所有患者均未发生严重感染或恶性肿瘤等严重药物不良反应，1例腹部皮下注射后出现腹痛、腹胀，持续3 d后症状消失；1例患者出现扁桃体炎，之后原有皮损处出现湿疹样改变；1例颈部出现化脓性淋巴结炎。结论 司库奇尤单抗治疗中重度斑块状银屑病疗效显著，不良反应较少，是中重度斑块状银屑病患者新的治疗选择之一。     

毛囊角化病ATP2A2基因突变二例及家系调查

【摘要】 例1男，16岁，面部、颈部及双腋下见密集褐色毛囊角化性丘疹，部分融合成斑块，局部可见疣状增生；母亲与其有相似的病史及临床表现。例2男，21岁，头面部、颈部、躯干、双腋下及臀部见弥漫性毛囊角化性丘疹，部分融合成片，局部可见疣状增生；家族成员均无类似症状。例2颈部皮损组织病理：表皮角化过度伴灶状角化不全，棘层部分区域棘刺松解并有腔隙形成，可见绒毛、圆体和谷粒细胞，真皮浅层炎症细胞浸润。2例患者及其父母基因检测：例1及母亲ATP2A2基因存在第15外显子c.2300A>G错义突变；例2第15外显子与第15内含子交界处存在c.2097+5G>A 剪切区域突变。2例患者其他家族成员未见上述突变。