Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity

Effector memory T cells (T_M) play a key role in the pathology of certain autoimmune disorders. The activity of effector T_M cells is under the control of Kv1.3 ion channels, which facilitate the Ca²⁺ influx necessary for T cell activation and function, i.e. cytokine release and proliferation. Consequently, the knock-down of Kv1.3 expression in effector T_M's may be utilized as a therapy for the treatment of autoimmune diseases. In this study we synthesized lipid unilamellar nanoparticles (NPs) that can selectively deliver Kv1.3 siRNAs into T_M cells in vitro. NPs made from a mixture of phosphatidylcholine, pegylated/biotinylated phosphoethanolamine and cholesterol were functionalized with biotinylated-CD45RO (cell surface marker of T_M's) antibodies via fluorophore-conjugated streptavidin (CD45RO-NPs). Incubation of T cells with CD45RO-NPs resulted into the selective attachment and endocytosis of the NPs into T_M's. Furthermore, the siRNA against Kv1.3, encapsulated into the CD45RO-NPs, was released into the cytosol. Consequently, the expression of Kv1.3 channels decreased significantly in T_M's, which led to a remarkable decrease in Ca²⁺ influx. Our results can form the basis of an innovative therapeutic approach in autoimmunity.     

Lack of association between hepatitis B virus pre‐S mutations and recurrence after surgical resection in hepatocellular carcinoma

Pre‐S mutation of hepatitis B virus (HBV) is known to be a risk factor for hepatocarcinogenesis. A previous study suggested that pre‐S mutation(s) may associate with increased recurrence after surgical resection. In the present study, 64 patients with HBV‐related hepatocellular carcinoma (HCC) were categorized into two groups according to the presence or absence of pre‐S mutation(s). The clinicopathological variables of the two groups were analyzed to assess the relationship between pre‐S mutations and postoperative recurrence. Nineteen patients (29.7%) had pre‐S mutations;13 had a pre‐S deletion, three had a pre‐S2 start codon mutation, two patients had both a pre‐S deletion, and a pre‐S2 start codon mutation, and one patient had a pre‐S2 insertion. The two groups did not differ in terms of baseline clinicopathological parameters. Cirrhosis and satellite lesion(s) were predictive factors for postoperative recurrence and poor overall survival. Recurrence‐free survival (P = 0.320) and overall survival (P = 0.238) did not differ significantly when pre‐S mutations were present. In conclusion, this study did not find evidence supporting the notion that pre‐S mutation(s) are associated with postoperative recurrence after surgical resection. J. Med. Virol. 85:589–596, 2013. © 2013 Wiley Periodicals, Inc.     

Probing the role of the right inferior frontal gyrus during Pain‐Related empathy processing: Evidence from fMRI and TMS

Recent studies have suggested that the right inferior frontal gyrus (rIFG) may be involved in pain‐related empathy. To verify the role of the rIFG, we performed a functional magnetic resonance imaging (fMRI) experiment to replicate previous research and further designed a noninvasive repetitive transcranial magnetic stimulation (rTMS) experiment to probe the causal role of the rIFG in pain‐related empathy processing. We assigned 74 volunteers (37 females) to three groups. Group 1 (n = 26) performed a task in which participants were required to perceive pain in others (task of pain: TP) and we used fMRI to observe the activity of the rIFG during pain‐related empathy processing. Then, we applied online rTMS to the rIFG and the vertex site (as reference site) to observe the performance of Group 2 (n = 24; performing TP) and Group 3 (n = 24; performing a control task of identifying body parts; task of body: TB). fMRI experiment demonstrated stronger activation in the rIFG than in the vertex during the perception of pain in others (p < .0001, Bonferroni‐corrected). rTMS experiment indicated that when the rIFG was temporarily disrupted, participants perceived pain in others significantly more slowly (p < .0001, Bonferroni‐corrected) than when the vertex was disrupted. Our results provide evidence that the rIFG is involved in pain‐related empathy processing, which yields insights into how the brain perceives pain in others.     

经皮椎弓根螺钉内固定术与小切口Wiltse入路椎弓根螺钉内固定术治疗胸腰椎骨折的短期疗效比较

目的 对比研究经皮椎弓根螺钉内固定术(PPS)与小切口Wiltse入路椎弓根螺钉内固定术(MWPS)治疗胸腰椎骨折的短期临床效果.方法 回顾性分析2018年2月—2020年2月四川省人民医院金牛医院骨一科收治的86例单节段胸腰椎骨折患者的临床资料,根据术式不同分为PPS组(41例)和MWPS组(45例).PPS组男性22例,女性19例;年龄18～70岁,平均48.9岁.致伤原因:高处坠落伤12例,道路交通伤25例,重物砸伤4例.MWPS组男性27例,女性18例;年龄18～70岁,平均49.0岁;致伤原因:高处坠落伤11例,道路交通伤28例,重物砸伤6例.比较两组患者的手术时间、术中出血量、术中透视时间、术后疼痛情况以及术后1个月Cobb角纠正程度、椎体高度恢复程度以及椎体复位情况.结果 MWPS组手术时间和术中透视时间分别为(73.58±5.73)min、(66.36±12.78)s,均明显少于PPS组[(85.74±5.82)min、(312.69±11.92)s],P<0.01;两组术中出血量分别为(68.62±3.63)mL、(69.65±3.72)mL,差异无统计学意义(P>0.05);MWPS组术后24h、7d、14d和1个月视觉模拟评分(VAS)明显低于PPS组[(5.8±0.7)分vs.(6.1±0.6)分、(3.3±0.7)分vs.(4.2±0.8)分、(2.1±0.1)分vs.(2.9±0.3)分、(1.1±0.1)分vs.(1.9±0.2)分],P<0.05;MWPS组置钉准确率和术后椎体复位率明显高于PPS组(91.85％vs.80.49％、88.89％vs.70.73％),P<0.05;MWPS组术后1个月椎体高度恢复程度和术后1个月Cobb角纠正程度均高于PPS组[(98.87±11.57)％vs.(97.58±11.65)％、(85.17±8.63)％vs.(82.91±8.87)％],但差异无统计学意义(P>0.05).结论 PPS与MWPS治疗胸腰椎骨折均具有良好的短期临床效果,但MWPS具有更高的置钉准确率和椎体复位率以及更低的辐射量,更能有效缓解患者术后的疼痛程度.     

Imaging Assessment of Visceral Pleural Surface Invasion by Lung Cancer: Comparison of CT and Contrast-Enhanced Radial T1-Weighted Gradient Echo 3-Tesla MRI

ObjectiveTo compare the diagnostic performance of contrast-enhanced radial T1-weighted gradient-echo 3-tesla (3T) magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of visceral pleural surface invasion (VPSI). Visceral pleural invasion by non-small-cell lung cancer (NSCLC) can be classified into two types: PL1 (without VPSI), invasion of the elastic layer of the visceral pleura without reaching the visceral pleural surface, and PL2 (with VPSI), full invasion of the visceral pleura.Materials and MethodsThirty-three patients with pathologically confirmed VPSI by NSCLC were retrospectively reviewed. Multidetector CT and contrast-enhanced 3T MRI with a free-breathing radial three-dimensional fat-suppressed volumetric interpolated breath-hold examination (VIBE) pulse sequence were compared in terms of the length of contact, angle of mass margin, and arch distance-to-maximum tumor diameter ratio. Supplemental evaluation of the tumor-pleura interface (smooth versus irregular) could only be performed with MRI (not discernible on CT).ResultsAt the tumor-pleura interface, radial VIBE MRI revealed a smooth margin in 20 of 21 patients without VPSI and an irregular margin in 10 of 12 patients with VPSI, yielding an accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F-score for VPSI detection of 91%, 83%, 95%, 91%, 91%, and 87%, respectively. The McNemar test and receiver operating characteristics curve analysis revealed no significant differences between the diagnostic accuracies of CT and MRI for evaluating the contact length, angle of mass margin, or arch distance-to-maximum tumor diameter ratio as predictors of VPSI.ConclusionThe diagnostic performance of contrast-enhanced radial T1-weighted gradient-echo 3T MRI and CT were equal in terms of the contact length, angle of mass margin, and arch distance-to-maximum tumor diameter ratio. The advantage of MRI is its clear depiction of the tumor-pleura interface margin, facilitating VPSI detection.     

Application of Q-TOF–MS based metabonomics techniques to analyze the plasma metabolic profile changes on rats following death due to acute intoxication of phorate

International Journal of Legal Medicine - Organophosphorus pesticides (OPS) are widely used in the world, and many poisoning cases were caused by them. Phorate intoxication is especially common in...     

Iodinated Contrast Media Can Induce Long-Lasting Oxidative Stress in Hemodialysis Patients

Purpose

Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population.

Materials and Methods

We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days.

Results

In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure.

Conclusion

Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients.     

Preventive Effect of Pretreatment with Intravenous Nicorandil on Contrast-Induced Nephropathy in Patients with Renal Dysfunction Undergoing Coronary Angiography (PRINCIPLE Study)

Purpose

To investigate the effect of pretreatment with intravenous nicorandil on the incidence of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing coronary angiography.

Materials and Methods

This randomized controlled multicenter study enrolled a total of 166 patients (nicorandil n=81; control n=85) with an estimated glomerular filtration rate <60 mL/min. Nicorandil 12 mg dissolved in 100 mL of 0.9% saline was administered intravenously for 30 minutes just prior to coronary angiography in the nicorandil group. The same volume of only saline was given to the control group. The primary end-point was the incidence of CIN, defined as >0.5 mg/dL increase or >25% rise in serum creatinine (SCr) concentration within 48 hours of contrast exposure compared to baseline.

Results

The final analysis included 149 patients (nicorandil n=73; control n=76). The baseline characteristics and the total volume of the used contrast (Iodixanol, 125.6±69.1 mL vs. 126.9±74.6 mL, p=0.916) were similar between the two groups. The incidence of CIN also did not differ between the nicorandil and control groups (6.8% vs. 6.6%, p=0.794). There was no difference between the two groups in the relative change in SCr from baseline to peak level within 48 hours after coronary angiography (-1.58±24.07% vs. 0.96±17.49%, p=0.464), although the nicorandil group showed less absolute change in SCr than the control group (-0.01±0.43 mg/mL vs. 0.02±0.31 mg/mL, p=0.005).

Conclusion

Prophylactic intravenous infusion of nicorandil did not decrease the incidence of CIN in patients with renal dysfunction undergoing coronary angiography.     

A Case of Cerebellar Infarction Caused by Acute Subclavian Thrombus Following Minor Trauma

Subclavian steal syndrome caused by an acute thrombus is very rare. We present a case of cerebellar infarction with proximal subclavian artery thrombosis. A 56-year-old woman was admitted for sudden vertigo. One day prior to admission, she received a shoulder massage comprised of chiropractic manipulation. On examination, her left hand was pale and radial pulses were absent. Blood pressure was weak in the left arm. Downbeat nystagmus and a right falling tendency were observed. Brain MRI showed multiple acute infarctions in the left cerebellum. The findings of Doppler ultrasonography in the left vertebral artery were compatible with a partial subclavian artery steal phenomenon. Digital subtraction angiography demonstrated a large thrombus in the left subclavian artery. After heparin infusion, thrombus size markedly decreased. Cerebellar infarction caused by acute subclavian thrombosis following minor trauma is rare, but the thrombus can be successfully resolved with anticoagulation.