抗PD-1/PD-L1免疫检查点抑制剂的皮肤免疫相关不良反应的研究进展

随着免疫检查点抑制剂（immune checkpoint inhibitors，ICPI）在国内外临床试验和应用中的逐步推广，越来越多的患者从免疫治疗中获得显著的疗效。其中抗程序细胞死亡蛋白1（programmed death-1，PD-1）及其配体（PD-1 ligand，PD-L1）免疫检查点抑制剂已被美国食品药品管理局（FDA）批准用于恶性黑色素瘤、转移性鳞状非小细胞肺癌、晚期肾癌、头颈鳞状细胞癌、尿路上皮癌等肿瘤的治疗。但PD-1/PD-L1单抗也会引起免疫相关性皮肤、消化道、肝脏、内分泌、肺部等器官的不良反应，皮肤毒性如皮疹、白癜风、皮肤干燥症等是最常见也是最早发生的不良反应。     

腭部恶性肿瘤的CT诊断

探讨腭部恶性肿瘤的CT表现及其诊断价值。回顾性分析32例经病理证实的腭部恶性肿瘤的CT表现,其中男27例,女5例。所有病例均行横断增强扫描,其中8例同时行平扫,2例加冠状位扫描。腭部恶性肿瘤的CT表现为:(1)腭部肿块(26例)、腭部软组织增厚(6例)和腭骨质破坏(6例),其中病变位于软腭(22例)、硬腭(4例)、软硬腭交界处(3例);(2)邻近结构受累及(27例);(3)颈部淋巴结转移(17例)。CT是一种优良的检查技术,能显示腭部恶性肿瘤的大体病理改变以及侵犯途径,为临床治疗和预后提供重要信息。     

化湿润燥方对干燥综合征模型小鼠颌下腺结构和功能的影响

目的：探索化湿润燥方对干燥综合征(SS)模型NOD/Ltj小鼠颌下腺组织病理损伤和功能的影响,以及对颌下腺细胞水通道蛋白5(AQP5)表达的调节作用。方法：以NOD/Ltj小鼠构建SS动物模型,选取9周龄雌性NOD/Ltj小鼠随机分为模型组、化湿润燥方组(7.15 g·kg^-1·d^-1)、硫酸羟氯喹(HCQ)组(1.30 g·kg^-1·d^-1),选取9周龄雌性BALB/c小鼠为正常组,每组6只。给药8周,记录各组小鼠饮水量、唾液流率,观察各组小鼠颌下腺病理染色结果并进行评分,采用免疫组化法(IHC)和蛋白免疫印迹法(Western blot)检测AQP5蛋白的表达水平。结果：与正常组比较,模型组小鼠饮水量明显增加(P<0.05)、唾液流率明显减低(P<0.05)。与模型组比较,化湿润燥方组小鼠饮水量明显降低(P<0.05)、唾液流率明显增加(P<0.05);HCQ组小鼠唾液流率明显增加(P<0.05)。颌下腺组织病理结果显示,与正常组比较,模型组小鼠病理评分、淋巴细胞浸...     

耳鸣相关脑区的正电子发射断层成像

目的　探讨与耳鸣相关的脑区并观察听力损失、耳鸣侧别、优势半球等因素的影响。方法　用正电子发射断层成像 (positronemissiontomograph ,PET)研究 17例耳鸣患者的脑葡萄糖代谢活动 ,并与 15例无耳鸣者作对照。示踪剂为18F标记的去葡萄糖。按有无听力损失将所有受试者分为 4组 ,第 1组耳鸣伴听力损失 ,13例 ;第 2组耳呜但听力正常 ,4例 ;第 3组无耳呜有听力损失 ,2例 ;第 4组无耳呜且听力正常 ,13例。用专门统计分析软件Statisticalparametersmapping(SPM)进行统计分析 ,按照Talairach坐标确定与耳呜相关脑区的解剖部位 (brodmannarea ,BA)。结果　耳呜相关脑区位于左侧颞横回 (BA41)、左侧颞上回 (BA42、2 2 )、左侧颞中回前部 (BA38)和左侧海马 ,这一结果不依赖于耳呜的侧别 ,而且与优势关球无关。听力损失相关的脑区主要是双侧颞上回后部 (BA42、2 2 )、颞中回中部 (BA2 1)、联合听区 (BA39)、左侧额中回 (BA8、9)、左侧额下回 (BA45 )等。结论　PET为主观耳呜提供了客观证据 ,有望成为耳呜的客观检测方法。     

大肠癌及癌旁粘膜p21~(ras)表达及意义

应用免疫组织化学方法对 12 8例人大肠癌及 32例不同距离癌旁粘膜进行研究。探讨 p2 1ras检测的临床病理学意义。结果 ,正常大肠粘膜、大肠癌、近癌旁粘膜、癌旁 1cm、2 cm、3cm及 5 cm粘膜 p2 1ras阳性率分别为 5 .0 % (1/ 2 0 )、5 2 .3% (6 7/ 12 8)、2 4.7% (18/ 73)、18.8% (6 / 32 )、15 .6 (5 / 32 )、9.4% (3/ 32 )及 9.4% (3/ 32 )。癌旁 3cm、5 cm粘膜的p2 1ras阳性率、阳性强度及分布均与正常粘膜相似 ,但癌旁 1cm、2 cm粘膜 p2 1ras阳性率较高且其中 5 0 %表达强度为(+ + )、(+ + + ) ,提示有 p2 1ras过表达现象。 p2 1ras表达与大肠癌临床病理因素无关。结论 :大肠癌中存在 p2 1ras过表达 ,且在癌旁 1cm、2 cm以内粘膜也存在 p2 1ras过表达可能 ,因此建议 ,在临床行大肠癌切除时 ,安全切缘至少在 3cm以上。     

Giant magneto-optical Raman effect in a layered transition metal compound

We report a dramatic change in the intensity of a Raman mode with applied magnetic field, displaying a gigantic magneto-optical effect. Using the nonmagnetic layered material MoS₂ as a prototype system, we demonstrate that the application of a magnetic field perpendicular to the layers produces a dramatic change in intensity for the out-of-plane vibrations of S atoms, but no change for the in-plane breathing mode. The distinct intensity variation between these two modes results from the effect of field-induced broken symmetry on Raman scattering cross-section. A quantitative analysis on the field-dependent integrated Raman intensity provides a unique method to precisely determine optical mobility. Our analysis is symmetry-based and material-independent, and thus the observations should be general and inspire a new branch of inelastic light scattering and magneto-optical applications.Raman scattering is an inelastic light scattering technique that has generated an enormous impact on the study of the functionality of crystalline solids for the last quarter of a century (1). In solids, Raman scattering can be used to observe the Raman active phonons as well as optical quasiparticles (plasmons and magnons). The intensity of any Raman active mode depends upon the symmetry of the crystal, the symmetry of the mode, the intermediate excited states, and the polarization of the incident and detected light (2). This has made Raman spectroscopy an extremely powerful technique for probing nascent symmetry and symmetry changes induced by internal or external perturbations. For example, Raman spectroscopy has been used to explore the effects of external pressure, temperature, field, defects, and doping (1, 3). From a phenomenological perspective, the application of a magnetic field is an effective way to manipulate electrons through Lorentz force in the intermediate state of the Raman process, thus modulating the electronic susceptibility that determines the Raman phonon intensity. In this study, we demonstrate a very large magneto-optical Raman effect in a classic layered, nonmagnetic material, MoS₂, driven by the broken symmetry induced by a magnetic field.Layered MoS₂ is an obvious prototype material because it has demonstrated promising optoelectronic applications at nanometer scale (4–10), is a quasi-2D material, and has two well-defined and clearly distinct Raman active phonon modes (11). The layered semiconductor MoS₂, which exhibits weak van der Waals coupling between neighboring layers, is structurally similar to graphite, and atomically thin flakes can be obtained from bulk crystals through mechanical exfoliation. Monolayer MoS₂ has an direct band gap of ∼1.9 eV, whereas the thicker members of the family of transition-metal dichalcogenides are indirect-gap (∼1.2 eV) semiconductors (12, 13). This material allows us to investigate the significance on the Raman intensity due to symmetry changes going from a single layer of MoS₂ to a bulk sample.Demonstrating a large magneto-optical Raman effect in a prototype compound is a fundamental breakthrough in the field of inelastic light scattering, allowing in principle the development of a new type of magneto-optical sensor. Magneto-optical applications are particularly important because these devices allow light intensity or polarization to be controlled using magnetic rather than electric or radiation fields. This control can greatly extend the optoelectronic application range and device-design degrees of freedom. The signal from conventional magneto-optical effects, such as the Kerr and Faraday effects, is generally weak, and an appreciable rotation of the light polarization requires sufficiently thick bulk materials. A magneto-optical coupling based on a different mechanism, such as the one demonstrated in this paper, would open new avenues for applications in atomically thin films or heterostructures.Monolayer and bilayer MoS₂ flakes were obtained through mechanical exfoliation from a natural MoS₂ single crystal (SPI Supplies) and transferred onto silicon wafers capped with 300-nm-thick SiO₂ by a method that is analogous to that used for production of graphene (Fig. S1). The bulk samples were obtained by cleaving single crystals. Atomically thin MoS₂ flakes were first visually identified by observing their interference color through an optical microscope. The thickness was further confirmed by measuring the frequency difference between the E_2g/E′ and A_1g/A′₁ Raman modes (Fig. S1) (11).Open in a separate windowFig. S1.(Upper) Optical images of MoS₂ samples in the form of (A) monolayer in the dashed region, (B) bilayer in the dashed region, and (C) bulk in the bright region. (Lower) Raman spectra from the corresponding three samples.Confocal micro-Raman measurements were performed in a backscattering configuration using a Jobin Yvon {"type":"entrez-nucleotide","attrs":{"text":"T64000","term_id":"667865","term_text":"T64000"}}T64000 system equipped with a back-illuminated (deep-depletion) CCD. A 532-nm diode-pumped solid-state laser (Torus 532; Laser Quantum) was used for the measurements. The laser was focused onto the samples with a spot size of 5–10 μm². The laser power was maintained at a level of 300 μW and monitored with a power meter (Coherent Inc.). Magnetic fields were generated up to 9 T using a superconducting magnet (Cryomagnetics) that has a room-temperature bore that is suitable for a microscope lens. The magnetic field direction was perpendicular to the sample surface. The 521-cm⁻¹ Raman mode of the Si substrate for supporting the mono- and bilayer of MoS₂ was also carefully monitored in the presence of magnetic fields; the intensities of the Si mode remained almost unchanged as the field was varied from 0 to 9 T in both the parallel and cross configurations (Fig. S2). Thus, the mode can be used to normalize the observed phonon intensities.Open in a separate windowFig. S2.(Left) Raman spectra of monolayer and (Right) bilayer MoS₂ under magnetic fields. The 521-cm⁻¹ mode from substrate silicon is also shown here for intensity comparison.A Stokes Raman process involving phonons is illustrated in Fig. 1A (1). Microscopically, Raman scattering is a three-step process: absorption of incoming photon for exciting the system to an intermediate excited state, phonon excitation by decaying to a lower-energy intermediate state, and emission of scattered photon by returning back to the ground state. Phonons are excited through electron–phonon interaction in the intermediate step. Naturally, the intensity of excited phonons reflected in Raman scattering spectra should be changed if the intermediate states of electrons are perturbed by magnetic field. The experimental schematic to realize such an idea is shown in Fig. 1B. A standard backscattering configuration is adopted in our experiments, that is, a linearly polarized incident light is normal to the surface of prototype material MoS₂ and the scattered light is also normal to the surface. A magnetic field is applied perpendicular to the sample surface (i.e., parallel to the incident and scattering light beam) to perturb the symmetry of electronic states.Open in a separate windowFig. 1.(A) A schematic of a three-step Raman excitation process where phonons are excited through the intermediate electronic states. (B) Schematic of experimental configuration. The incident light polarization (e_i) is along the x direction whereas the scattered light polarization (e_s) can be along either the x (parallel) or y (perpendicular) direction, and magnetic fields are perpendicular to the sample plane (i.e., along the z direction). A field-driven transverse component of electron motions under radiation field is illustrated, which effectively gives rise to a rotation of the polarization plane of the scattered light. Raman spectra of monolayer MoS₂ of (C) parallel and (D) perpendicular polarization configurations with and without the magnetic field. The vibrational patterns of the corresponding E and A Raman modes are illustrated in the insets.MoS₂ has a honeycomb-lattice structure similar to that of graphite. Mo atoms are sandwiched by neighboring S planes in a separate MoS₂ layer (Fig. 1B), with the point-group symmetry of D_6h in the bulk, which becomes D_3d in the bilayer case. In monolayer form, the symmetry is further reduced to D_3h due to the disappearance of the inversion center (Fig. 1C, Inset (11). The symmetries of the two modes are changed from bulk to bi- and monolayer because of the reduction of point-group symmetry mentioned above (11).

Table 1.

A- and E-mode symmetries with and without magnetic field in MoS₂

Bistable electrical switching and nonvolatile memory effects by doping different amounts of GO in poly(9,9-dioctylfluorene-2,7-diyl)

Poly(9,9-dioctylfluorene-2,7-diyl) (PFO) was synthesized under a Suzuki coupling reaction, and its structure was proved by Fourier transform infrared (FT-IR) spectroscopy, and hydrogen and carbon nuclear magnetic resonance (¹H-NMR and ¹³C-NMR). A nonvolatile organic memristor, based on active layers of PFO and PFO:GO composite, was prepared by spin-coating and the influence of GO concentration on the electrical characteristics of the memristor was investigated. The results showed that the device had two kinds of conductance behavior: electric bistable nonvolatile flash memory behavior and conductor behavior. With an increase in GO concentration, the device has an increased ON/OFF current ratio, increasing from 2.1 × 10¹ to 1.9 × 10³, a lower threshold voltage (V_SET), decreasing from −1.1 V to −0.7 V, and better stability. The current remained stable for 3 hours in both the ON state and OFF state, and the ON and OFF state current of the device did not change substantially after 9000 read cycles.

The device shows different conductive behavior: electric bistable nonvolatile flash memory behavior and conductor behavior.     

罗氏标本前处理系统离心参数的优化

目的 优化标本前处理系统离心参数,降低标本凝集率,提高标本前处理系统的标本处理效率.方法 对比低温离心和常温离心的标本凝集率;对比低离心力长时间离心和高离心力短时间离心标本凝集率.结果 设置为离心力1822×g、离心时间5 min时,20℃离心标本凝集率低于10℃离心标本凝集率[(3.44±0.24)％vs.(4.70±0.44)％,P<0.05];设置为离心力4100×g、离心时间5 min的标本凝集率低于设置离心力1822×g、时间10 min的标本凝集率[(0.30±0.03)％vs.(2.88±0.27)％,P<0.05].电化学发光检测项目癌胚抗原(CEA)、神经元特异烯醇化酶(NSE)、乙型肝炎表面抗原(HBsAg)的标本分别经1822×g和4100×g离心前处理后进行检测,对检测结果进行比较,差异均无统计学意义(P>0.05).结论 对电化学发光检测而言,常温的离心效果优于低温离心,高离心力短时间离心比低离心力长时间离心的标本凝集率低.标本前处理系统设置合理的离心参数能够节省标本预处理时间,提高检测效率.     

CTGF和ELMO1多态性与2型糖尿病性肾病易感性的关联研究

目的探讨结缔组织生长因子(CTGF) rs2648875及吞噬和细胞运动蛋白１(ELMO1) rs10951509多态性与2型糖尿病性肾病(DKD)的相关性。方法收集195例汉族DKD患者（DKD组）,同时选取134例健康人群作为对照组。收集两组患者的体质量、身高、血压、血生化等临床资料。采用imLDRTM多重SNP分型试剂盒检测基因多态性。结果两组患者的CTGF rs2648875基因型AA,GA和GG分布比较,差别具有统计学意义(P＜0.05);DKD组风险等位基因A频率较对照组升高(P=0.007);GG基因型患者的甘油三酯水平较AA和GA基因型患者显著降低(P<0.05)。两组患者的ELMO1 rs10951509基因型AA,AG和GG分布比较,差别具有统计学意义(P=0.034);DKD组风险等位基因A频率较对照组升高(P=0.009);AG基因型患者低密度脂蛋白胆固醇水平较AA基因型患者显著降低(P<0.05)。Logistic回归分析证实,吸烟史、腹型肥胖、收缩压、空腹血糖、尿素氮、CTGF\|AA基因型为DKD的独立危险因素。结论CTGF rs2648875及ELMO1 rs10951509与DKD的遗传易感性相关,携带CTGF rs2648875等位基因A及ELMO1 rs10951509等位基因A可增加DKD的风险