可切除非小细胞肺癌患者术后奥西替尼靶向治疗分析

目的分析可切除非小细胞肺癌(NSCLC)患者术后奥希替尼靶向治疗的效果。 方法2018年1月至2018年12月我院收治的53例可切除NSCLC患者为对象,其术后联合奥希替尼治疗。检测经奥希替尼治疗前后的血清生长转化因子-α(TGF-α)、癌胚蛋白(CEA)、细胞角蛋白19片段抗原21-1(CA21-1)水平,评估奥希替尼在治疗可手术切除的NSCLC中的疗效。 结果经奥希替尼治疗2个月后,行手术切除NSCLC患者血清TGF-α[(14.39±1.47)μg/L vs.(9.86±1.76)μg/L]、CEA[(9.63±1.86)ng/ml vs.(6.69±1.15)ng/ml]以及CA21-1[(5.31±1.49)μg/L vs.(2.31±0.53)μg/L]水平均下降(t＝14.382、9.788、13.810,P<0.05);奥希替尼治疗后不良反应为皮疹,其次为腹泻及瘙痒,但以上不良反应为轻度,经治疗后减轻;随访2年,7例死亡,46例患者存活;15例疾病进展,疾病中位无进展生存时间(mPFS)16.5个月。COX多因素分析提示,中高分化是手术切除NSCLC患者奥希替尼治疗后疾病无进展生存时间。绘制生存曲线发现,低分化者生存率低于中高分化者,差异具有统计学意义(Rank＝4.924,P<0.05)。 结论奥希替尼可进一步提高NSCLC患者肺癌根治术效果,在中高分化者中的应用具有临床意义。     

《自体富血小板血浆制备技术专家共识》解读

［摘要］　为更好地帮助读者对《自体富血小板血浆制备技术专家共识》（简称《共识》）进行理解,该文对《共识》中的重点推荐点、难点和疑惑点作了较为系统的解释或补充说明。以期为读者更全面认识、准确理解和灵活运用《共识》提供支撑,最大限度地推动该技术在输血医学领域的健康发展。     

输血医学科开展自体富血小板血浆治疗新技术的思考

［摘要］　根据我国输血医学相关的法规、技术文件和富血小板血浆（PRP）新技术的特点,结合南部战区总医院输血医学科的研究及开展该技术10余年的实际经验,该文对PRP国内外研究现状、开展必要性、具有的优势、如何开展及应用前景等方面进行阐述,旨在为输血医学科进一步开展自体PRP治疗新技术提供参考。     

Synthesis and Bio‐Evaluation of New 18F‐Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice

To improve the stability of ¹⁸F‐labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([¹⁸F]FPTP2, [¹⁸F]FPTP‐P2, and [¹⁸F]FPTP‐P3) were synthesized with ‘side chain’ modifications. The radiolabeled tracers and corresponding non‐radioactive compounds were obtained by substituting tosyl group with ^18/19F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70–90 min with high decay‐corrected radiochemical yields (36–65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [¹⁸F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart‐to‐liver, heart‐to‐lung, and heart‐to‐blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [¹⁸F]FPTP2 suggest that the substitution of the phenyl ‘sidechain’ with other non‐phenyl rings has no effect on the myocardial targeting property of ¹⁸F‐labeled pyridaben analogs.     

Left ventricular opacification after peripheral venous injection of a modified albumin solution.

The usefulness of a modified albumin solution was assessed in 8 dogs after peripheral venous and inferior vena cava injections. The contrast agent is a mixed solution made of glucose, albumin and glycerin, with sonicated microbubble diameter of 5.0 +/- 2.3 microns. Multiple injections (8 ml each) of this contrast agent (total 80 injections) into peripheral vein and inferior cava were performed. The blood pressure from femoral artery was measured before, during and after injections. Two-dimensional echocardiograms were recorded in a modified long axis view on videotapes for play back analysis. The pulmonary transit time and left ventricular contrast persistent time was determined for each injection. The videodensity of the region of interest (ROI) at the center of right ventricle and left ventricle was measured. The background videodensity of both ventricles was evaluated. The videodensity over the ROI of both ventricles with peak contrast enhancement was measured in all frames for 3 consecutive cardiac cycles. The peak videodensity of right and left ventricle subtracting the background videodensity of each ventricles was further calculated respectively. The injections caused no change in blood pressure or heart rate. All injections produced right ventricular contrast echo. As much as 85% of peripheral venous and 82.5% of inferior vena cava injections resulted in left ventricular contrast which was 0.68 and 0.65 as bright as that produced in the right ventricle. Pulmonary transit time and left ventricle contrast persistent time of peripheral venous injection was 4.05 +/- 0.53 and 13.67 +/- 4.28 seconds respectively. No difference of these data (3.93 +/- 0.47 and 11.65 +/- 4.66 seconds) from those produced by inferior vena cava injections were noted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrent deep neck abscess and piriform sinus tract: A 15-year review on the diagnosis and management

Background

Piriform sinus tract (PST) is a rare congenital condition. A delay in diagnosis is common leading to recurrent inflammation.

Method

A retrospective review was performed on all cases of PST treated at a tertiary referral centre between May 1997 and May 2012.

Results

Eighteen patients were reviewed with a mean age of 5.4 years at presentation (ranged from 0 day to 14 years). Most patients presented as acute inflammation (88.9%) and 16 had a left sided lesion. 72.2% of the PST are identified by contrast swallow study. The diagnostic yield was significantly higher if the study was done after the initial acute inflammation settled. Ultrasonography and computer tomography are less sensitive. The median duration from presentation to diagnosis was 17.6 months (ranged 0–120 months). Ten patients (55.6%) experienced recurrent inflammation before confirming the diagnosis. Fistulectomy alone was performed in 15 patients while an additional en-bloc hemithyroidectomy was done in 2 patients.

Conclusion

PST should be suspected in children presenting with a left deep neck abscess. Contrast swallow study is very effective in making diagnosis but has to be postponed after the acute inflammation settles. The condition can be effectively treated by fistulectomy without hemithyroidectomy in majority of our cases.     

Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module

Our previous study showed that when glutamate receptor （GluR）6 C terminus-containing peptide conjugated with the human immunodeficiency virus Tat protein （GluR6）-9c is delivered into hippocampal neurons in a brain ischemic model, the activation of mixed lineage kinase 3 （MLK3） and c-Jun NH2-terminal kinase （JNK） is inhibited via GluR6-postsynaptic density protein 95 （PSD95）. In the present study, we investigated whether the recombinant adenovirus （Ad） carrying GluR6c could suppress the assembly of the GluR6-PSD95-MLK3 signaling module and decrease neuronal cell death induced by kainate in hippocampal CA1 subregion. A seizure model in Sprague-Dawley rats was induced by intraperitoneal injections of kainate. The effect of Ad- Glur6-9c on the phosphorylation of INK, MLK3 and mitogen-activated ldnase kinase 7 （MKK7） was observed with western immunoblots and immunohistochemistry. Our findings revealed that overexpression of GluR6c inhibited the interaction of GluR6 with PSD95 and prevented the kainate-induced activation of INK, MLK3 and MKK7. Furthermore, kainate-mediated neuronal cell death was significantly suppressed by GluR6c. Taken together, GluR6 may play a pivotal role in neuronal cell death.     

Electronic evidence of an insulator–superconductor crossover in single-layer FeSe/SrTiO3 films

In high-temperature cuprate superconductors, it is now generally agreed that superconductivity is realized by doping an antiferromagnetic Mott (charge transfer) insulator. The doping-induced insulator-to-superconductor transition has been widely observed in cuprates, which provides important information for understanding the superconductivity mechanism. In the iron-based superconductors, however, the parent compound is mostly antiferromagnetic bad metal, raising a debate on whether an appropriate starting point should go with an itinerant picture or a localized picture. No evidence of doping-induced insulator–superconductor transition (or crossover) has been reported in the iron-based compounds so far. Here, we report an electronic evidence of an insulator–superconductor crossover observed in the single-layer FeSe film grown on a SrTiO₃ substrate. By taking angle-resolved photoemission measurements on the electronic structure and energy gap, we have identified a clear evolution of an insulator to a superconductor with increasing carrier concentration. In particular, the insulator–superconductor crossover in FeSe/SrTiO₃ film exhibits similar behaviors to that observed in the cuprate superconductors. Our results suggest that the observed insulator–superconductor crossover may be associated with the two-dimensionality that enhances electron localization or correlation. The reduced dimensionality and the interfacial effect provide a new pathway in searching for new phenomena and novel superconductors with a high transition temperature.The iron-based superconductors (1–4) represent the second class of high-temperature superconductors after the discovery of the first class of high-temperature cuprate superconductors. It is now generally agreed that the superconductivity in cuprates is realized by doping a Mott (charge transfer) insulator (5). In the iron-based superconductors, however, the parent compounds mostly exhibit a poor metallic behavior with an antiferromagnetic order, thus raising a debate on whether an appropriate starting point should go with an itinerant picture or a localized picture (6–18), particularly whether the picture of doping a Mott insulator is relevant to the iron-based superconductors (1, 3, 11, 16, 17). Some theoretical calculations indicate that the iron-based superconductors may be in proximity to a Mott insulator (11, 16, 17), and attempts have also been made to unify cuprates and iron-based superconductors in theory (18). However, so far no clear experimental evidence of doping (or carrier concentration)-induced insulator–superconductor transition (or crossover) has been reported in the iron-based superconductors.The latest discovery of possible high-temperature superconductivity in the single-layer FeSe films grown on a SrTiO₃ substrate has attracted much attention both experimentally (19–27) and theoretically (28–32). The reduced dimensionality with enhanced interfacial effect makes this system distinct from its bulk counterpart. First, it has a simple crystal structure that consists of a single-layer Se-Fe-Se unit, which is an essential building block of the iron-based superconductors (19). Second, the superconducting single-layer FeSe/SrTiO₃ film possesses a distinct electronic structure that exhibits only electron pockets near the Brillouin zone corner without any Fermi crossing near the zone center (20–22). In particular, it was found that annealing in vacuum can tune the carrier concentration of the FeSe/SrTiO₃ films (21, 33), thus providing a good opportunity to investigate its carrier-dependent behaviors.In this paper, to our knowledge, we report the first observation of an insulator–superconductor crossover in the iron-based superconductors by performing systematic angle-resolved photoemission (ARPES) measurements on the single-layer FeSe/SrTiO₃ films at various carrier concentrations. At a very low carrier concentration, the spectral weight near the Fermi level is suppressed, accompanied with the opening of an insulating energy gap. When the carrier concentration increases, the spectral weight begins to fill in the insulating gap, resulting in a decrease in gap size with the formation and sharpening of the peak at the Fermi level. Eventually, when the carrier concentration increases to a critical value, the insulating gap closes and superconductivity starts to emerge. The overall evolution in the single-layer FeSe/SrTiO₃ film is quite similar to the insulator–superconductor transition observed in the cuprate superconductors (34–38). Our observations have established a clear case that an insulator–superconductor crossover takes place with increasing carrier concentration in a 2D iron-based superconductor. The similarities between the current observations and those in cuprates provide new insights in understanding the superconductivity mechanism in these systems. The observed insulator–superconductor crossover in the single-layer FeSe/SrTiO₃ film points to the significant role of the reduced dimensionality in dictating the physical properties and superconductivity.     

Trans-Caryophyllene Suppresses Hypoxia-Induced Neuroinflammatory Responses by Inhibiting NF-κB Activation in Microglia

Microglia cells have been reported to mediate hypoxia-induced inflammation through the production of proinflammatory cytokines, including interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6. Given the fact that the activation of the type 2 cannabinoid receptor (CB2R) provides antioxidative and anti-inflammatory results, it is suspected that its selective agonist, trans-caryophyllene (TC), may have protective effects against hypoxia-induced neuroinflammatory responses. In this study, TC was found to significantly inhibit hypoxia-induced cytotoxicity as well as the release of proinflammatory cytokines, including IL-1β, TNF-α, and IL-6, through activation of BV2 microglia following hypoxic exposure (1 % O₂, 24 h). Furthermore, TC significantly inhibited hypoxia-induced generation of reactive oxygen species (ROS) in mitochondria as well as the activation of nuclear factor kappa B (NF-κB) in microglia. Importantly, TC’s effects on inhibiting the activation of NF-κB and the secretion of inflammatory cytokines can be abolished by muting the CB2R using small RNA interference. These observations indicate that TC suppresses the hypoxia-induced neuroinflammatory response through inhibition of NF-κB activation in microglia. Therefore, TC may be beneficial in preventing hypoxia-induced neuroinflammation.     

Astragaloside IV attenuates renal tubulointerstitial fibrosis by inhibiting p38 MAPK signaling

Objective To investigate the effect of astragaloside IV (AS-IV) on renal tubulointerstitial fibrosis and its regulation on p38 MAPK signaling. Methods In vivo, UUO model with renal tubulointerstitial injury was constructed. Mice in AS-IV group were orally administrated AS-IV 20 mg•kg-1•d-1 for 7 days after operation, and mice in other groups were administrated the equal volume vehicle. Bilateral kidneys were collected in 7 and 14 days after operation. Transverse kidney slices were stained with Masson trichrome to evaluate the severity of renal tubule injury. In vitro, normal human renal tubular epithelial cells (HK-2) were stimulated with recombinant TGF-β1 (10 ng/ml) and simultaneously treated with different concentrations of AS-IV (0, 50, 100, 200 μg/ml) for 24 h. SB203580 (10 μmol/L) was also ultilized to pre-treat HK-2 cells for 1 h to inhibit phosphorylation of p38 MAPK signaling. The expression of FN, Col IV, and α-SMA were investigated by western blotting and real-time PCR. The expression of p-p38 MAPKs were also observed by Western Blotting. Results Astragaloside IV morphologically ameliorated renal tubulointerstitial fibrosis. The proteins and mRNA expression of FN, Col IV, α-SMA, and TGF-β1 were also increased significantly in UUO kidney tissues (all P＜0.05), which could be reversed by AS-IV administration (all P＜0.05). In vitro, the expression of FN, Col IV, and α-SMA were up-regulated by TGF-β1 after stimulating for 24 h (all P＜0.05), which were decreased by AS-IV. The inhibition effect on FN and α-SMA were similar between AS-IV and MAPK inhibitor SB203580. AS-IV inhibited p-p38 MAPK signals both in vivo and in vitro. Conclusions AS-IV could attenuate renal tubulointerstitial fibrosis induced by UUO and TGF-β1 through reducing FN、Col IV、α-SMA expression in renal tubular cells. The mechanism of AS-IV protective effect might be associated with inhibition of p38 MAPK phosphorylation.