赛沃替尼治疗MET基因突变非小细胞肺癌的药物浓度与疗效和不良反应的关系

目的:探讨药物浓度与疗效和不良反应之间的关系,了解赛沃替尼治疗MET14外显子跳跃突变晚期非小细胞肺癌患者的疗效和安全性。方法:回顾性分析2018年4月至2019年9月北京大学肿瘤医院收治的携带MET14外显子跳跃突变,并且接受赛沃替尼治疗的16例局部晚期或转移性非小细胞肺癌患者的临床资料及其血浆药物浓度,评估赛沃替尼治疗的疗效和安全性,分析药物浓度与疗效及不良反应的相关性。随访患者的无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS),采用Kaplan-Meier法计算中位PFS和OS。结果:16例患者中男性9例(56.3%),年龄范围51~84岁。肺癌病理类型包括:腺癌11例,肉瘤样癌5例,鳞癌1例。赛沃替尼的客观缓解率为50.0%(8/16),疾病控制率达到87.5%(14/16)。评效达到部分缓解患者和未达到者相比,赛沃替尼的药物谷浓度分别为77.2 ng/mL和146.7 ng/mL(P=0.06)。治疗中出现过2级以上不良反应的患者和仅出现过1级不良反应者,其药物谷浓度分别为116.5 ng/mL和93.2 ng/mL(P=0.59)。所有患者的中位PFS为8.5个月,中位OS为14.1个月。结论:赛沃替尼治疗MET基因突变非小细胞肺癌的效果较好,不良反应可耐受。常规用药剂量下,赛沃替尼的血浆药物谷浓度与疗效可能存在一定负相关,但药物浓度与不良反应的程度无明显相关性。

影响恶性肿瘤诊治的非肿瘤性疾病分析

目的:了解恶性肿瘤患者合并的非肿瘤性疾病情况,探讨非肿瘤性疾病对肿瘤患者诊疗方案的影响。方法:收集2013年1月1日至2017年12月31日北京大学肿瘤医院住院患者经院际会诊的1 323例病历资料,筛选其中合并非肿瘤性疾病的病例。回顾性分析该组患者的临床病历资料,探讨非肿瘤性疾病在肿瘤诊治过程中的影响。结果:本研究1 323例院际会诊病例中,筛选出非肿瘤性疾病1 153例(87.2%),其中男性773例(67.0%),女性380例(33.0%)。年龄为14~90岁,中位年龄62岁。原发肿瘤类型包括:肺癌、胃癌、淋巴瘤、结直肠癌、食管癌、乳腺癌、恶性黑色素瘤、肝癌、胆管癌/胆囊癌、胰腺癌和其他肿瘤。非肿瘤性疾病情况为心血管疾病356例(30.9%),呼吸系统疾病196例(17.0%),消化系统疾病107例(9.3%),皮肤病及性病81例(7.0%),神经系统病变74例(6.4%),泌尿系统疾病72例(6.2%),血液系统疾病70例(6.1%),内分泌与代谢性疾病47例(4.1%),自身免疫性疾病23例(2.0%),其他疾病127例(11.0%)。直接影响肿瘤诊疗方案的制定为771例(66.9%);不影响方案的制定为313例(27.1%);不确定/无法判断的为69例(6.0%)。结论:心血管疾病是恶性肿瘤患者合并的主要非肿瘤性疾病。非肿瘤性疾病是影响恶性肿瘤诊疗方案制定的重要因素。

可光聚合氟硅聚合物的研究进展

简述了可光聚合含氟聚合物、可光聚合有机硅聚合物和可光聚合氟硅聚合物的结构与性能、种类和发展方向,指出了可光聚合氟硅聚合物在今后发展中的重要性。

Flexible, Porous, and Metal–Heteroatom?Doped Carbon Nanofibers as Efficient ORR Electrocatalysts for Zn–Air Battery

Developing an e cient and durable oxygen reduction electrocatalyst is critical for clean-energy technology, such as fuel cells and metal–air batteries. In this study, we developed a facile strategy for the preparation of flexible, porous, and well-dispersed metal–heteroatom-doped carbon nanofibers by direct carbonization of electrospun Zn/Co-ZIFs/PAN nanofibers(Zn/Co-ZIFs/PAN). The obtained Zn/Co and N co-doped porous carbon nanofibers carbonized at 800 °C(Zn/Co–N@PCNFs-800) presented a good flexibility, a continuous porous structure, and a superior oxygen reduction reaction(ORR) catalytic activity to that of commercial 20 wt% Pt/C, in terms of its onset potential(0.98 V vs. RHE), half-wave potential(0.89 V vs. RHE), and limiting current density(-5.26 mA cm^(-2)). In addition, we tested the suitability and durability of Zn/Co–N@PCNFs-800 as the oxygen cathode for a rechargeable Zn–air battery. The prepared Zn–air batteries exhibited a higher power density(83.5 mW cm^(-2)), a higher specific capacity(640.3 mAh g^(-1)), an excellent reversibility, and a better cycling life than the commercial 20 wt% Pt/C + RuO_2 catalysts. This design strategy of flexible porous non-precious metal-doped ORR electrocatalysts obtained from electrospun ZIFs/polymer nanofibers could be extended to fabricate other novel, stable, and easy-to-use multi-functional electrocatalysts for clean-energy technology.

Fast track clinical pathway implications in esophagogastrectomy

AIM： To investigate the feasibility of fast track clinica pathway for esophageal tumor resections. METHODS： One hundred and fourteen patients with esophageal carcinoma who underwent esophagogastrectomy from January 2006 to October 2007 in our department were studied. Fast track clinical pathway included analgesia control, fluid infusion volume control, early ambulation and enteral nutrition. Nasogastric tube was removed 3 d after operation and chest tube was removed 4 d after operation as a routine, and full liquid diet 5 d after operation. RESULTS： Among 114 patients （84 men and 30 women）, 26 patients underwent fast track surgery, including 17 patients over 65 years old and 9 under 65 （P = 0.014）; 18 patients who had preoperative complications could not bear fast track surgery （P 〈 0.001）. No significant differences in tolerance of fast track surgery were attributed to differences in gender, differentiated degree or stage of tumor, pathological type of tumor, or operative incision. The median length of hospital stay was 7 d （5-28 d）, 4% patients were readmitted to hospital within 30 d of discharge. Three patients died and postoperative mortality was 2.6%. All 3 patients had no determinacy to fast track surgery approach.CONCLUSION： The majority of patients with esophageal carcinoma can tolerate fast track surgery. Patients younger than 65 or who have no preoperative diseases have the best results. Median length of hospital stay has been reduced to 7 d.

Photopolymerization induced by a benzophenone derivative photoinitiator

A benzophenone derivative photoinitiator, HBP-TDI-HQ-TDI-HBP （HTCTH）, was synthesized based on 4-hydroxy benzophenone （HBP）, toluene-2,4-diisocyanate （TDI） and hydroquinone （HQ）. HTCTH was a more effective photoinitiator which had longer wavelength absorption in the UV-vis absorption spectra than the low molecular counterpart benzophenone （BP）. It showed that both rate of polymerization （Rp） and final conversion （P） increased with increase of amine and HTCTH concentration in photopolymerization.

聚乳酸/氧化石墨烯阻隔、阻燃多功能薄膜的制备及其性能研究

本文通过Hummers法制备氧化石墨烯(GO),并通过层层自组装的方法将其与壳聚糖(CS)和聚磷酸铵(APP)组成的阻隔阻燃体系一起应用于聚乳酸(PLA)薄膜表面,制备PLA/GO/CS-APP复合多功能薄膜。通过傅立叶变换红外光谱(FTIR)、3D光学数码显微镜和扫描电子显微镜(SEM)对复合PLA薄膜的表面化学结构及微观形貌进行了表征,并对复合薄膜的阻燃性能,热稳定性和透氧率进行了测试。实验表明,GO,CS和APP可通过静电吸附于PLA表面,同时对PLA薄膜的热稳定性、阻燃性能和阻隔性均有所提高。

Preparation and characterization of crosslinked chitosan-based nanofibers

Crosslinked chitosan-based nanofibers were successfully prepared via clectrospinning technique with heat mediated chemical crosslinldng followed. The structure, morphology and mechanical property of nanofibers were characterized by attenuated total reflection-Fourier transform infrared spectroscopy （ATR-FTIR）, scanning electron microscopy （SEM）, Instron rnachine, respectively. The results showed that, nanofibers exhibited a smooth surface and regular morphology, and tensile strength of nanofibers improved with increasing of triethylene glycol dimethacrylate （TEGDMA） content.

Differences in the primary culture, purification and biological characteristics between endothelial cells and smooth muscle cells from rat aorta

Objective： To investigate the differences of primary culture, purification and biological characteristics between endothelial cells and smooth muscle cells from rat aorta. Methods： Endothelial cells were obtained using the vascular ring adherence, collagenase digestion method and an improved vascular ring adherence method, while smooth muscle cells were separated from tissue sections of rat aorta. Clones of endothelial cells were selected by limiting dilution assay. Both cell types were identified using specific cell immunofluorescent markers, and phase contrast microscopy was used to observe the morphological disparity between endothelial cells and smooth muscle cells at the single cell and colony level. Cell proliferation was determined by the cell counting kit-8. Differences between endothelial cells and smooth muscle cells were evaluated in trypsin digestion time, attachment time and recovery after cryopreservation. Results： Endothelial cells were obtained by all three methods. The improved vascular ring method provided the most reproducible results. Cells were in good condition, and of high purity. Smooth muscle cells were cultured successfully by the tissue fragment culture method. Clonal expansion of single endothelial cells was attained. The two cell types expressed their respective specific markers, and the rate of proliferation of smooth muscle cells exceeded that of endothelial cells. Endothelial cells were more sensitive to trypsin digestion than smooth muscle cells. In addition, they had a shorter adherence time and better recovery following cryopreservation than smooth muscle cells. Conclusion： The improved vascular ring method was optimal for yielding endothelial cells. Limiting dilution is a novel and valid method for purifying primary endothelial cells from rat aorta. Primary rat endothelial cell and vascular smooth muscle cell cultures exhibited different morphological characteristics, proliferation rate, adherence time, susceptibility to trypsin digestion and recovery after cryopreservation. Our research can be a good foundation for further application in the regeneration of blood vessel.

3D Interconnected Honeycomb‑Like Multifunctional Catalyst for Zn-Air Batteries

Developing high-performance and low-cost electrocatalysts is key to achieve the clean-energy target.Herein,a dual regulation method is proposed to prepare a 3D honeycomb-like carbon-based catalyst with stable Fe/Co co-dopants.Fe atoms are highly dispersed and fixed to the polymer microsphere,followed by a high-temperature decomposition,for the generation of carbon-based catalyst with a honeycomb-like structure.The as-prepared catalyst contains a large number of Fe/Co nanoparticles(Fe/Co NPs),providing the excellent catalytic activity and durability in oxygen reduction reaction,oxygen evolution reaction and hydrogen evolution reaction.The Zn-air battery assembled by the as-prepared catalyst as air cathode shows a good charge and discharge capacity,and it exhibits an ultra-long service life by maintaining a stable charge and discharge platform for a 311-h cycle.Further X-ray absorption fine structure characterization and density functional theory calculation confirms that the Fe doping optimizes the intermediate adsorption process and electron transfer of Co.

Three-dimensional,isotropic imaging of mouse brain using multi-view deconvolution light sheet microscopy

We present a threedimensional(3D)isotropic imaging of mouse brain using light-sheet fuo-rescent microscopy(LSFM)in conjumction with a multi-view imaging computation.Unlike common single view LSFM is used for mouse brain imaging,the brain tissue is 3D imaged under eight views in our study,by a home-built selective plane ilumination microscopy(SPIM).An output image containing complete structural infornation as well as significantly improved res olution(~4 times)are then computed based on these eight views of data,using a bead-guided multi-view registration and deconvolution.With superior imaging quality,the astrocyte and pyrarmidal neurons together with their subcellular nerve fbers can be clearly visualized and segmented.With further incuding other computational methods,this study can be potentially scaled up to map the conectome of whole mouse brain with a simple light.sheet microscope.

A natural component as initiator for photopolymerization of 1,6-hexanedioldiacrylate

1,3-Benzodioxole (BDO) as a simple model compound for the BDO derivatives from natural plant was used as coinitiator for p-chlorobenzophenone (CBP) and initiator for UV photopolymerization of 1,6-hexanedioldiacrylate (HDDA), respectively. The results showed that, BDO was an effective coinitiator for CBP. Although BDO as initiator led to very low rate of polymerization, it was still meaningful for the photocuring field.

Photo-curing 3D printing technique and its challenges

In recent ten years,3D printing technology has been developed rapidly.As an advanced technology,3D printing has been used to fabricate complex and high-precision objects in many fields.3D printing has several technologies.Among these technologies,photo-curing 3D printing was the earliest and most mature technology.In 1988,the first 3D printing machine which was based on photo-curing and called Stereo lithography Appearance(SLA)technology was produced by 3D system Corp.After 30 years of development,many new technologies based on photocuring mechanism emerged.Based on the different principle of pattern formation and character of printing technology,numerous photocuring 3D printing techniques,such as SLA,DLP,LCD,CLIP,MJP,twophoton 3D printing,holographic 3D printing and so on,have been developed.Photo-curing 3D printing has many advantages,such as high precision,smooth surface of printing objects,rapid printing speed and so on.Here,we would introduce five industrial photocuring 3D printing technologies,which are SLA,DLP,LCD,CLIP and MJP.The characters of the materials and the progress of the application of the technique in the biomedical field is also overviewed.At last,the difficulties and challenges of photo-curing 3D printing are also discussed.

Electrospun Core-Shell Fibrous 2D Scaffold with Biocompatible Poly(Glycerol Sebacate) and Poly-l-Lactic Acid for Wound Healing

Biomimetic scaffolds made by synthetic materials are usually used to replace the natural tissues aimed at speeding up the skin regeneration.In this study,a flexible and cytocompatible poly(glycerol sebacate)@poly-l-lactic acid(PGS@PLLA)fibrous scaffold with a core-shell structure was fabricated by coaxial electrospinning,where the shell PLLA was used to be a skeleton with pores on the fibrous surface.The fibrous morphology with pores on the surface of the prepared fibers was observed by SEM.The core-shell microstructure of PGS@PLLA fibers was confirmed by TEM and Laser Scanning Confocal Microscopy(LSCM).In addition,the prepared fibers exhibited a strong ability to repair tissues of the skin wound,where the stability of cell security and proliferation,and the lower inflammatory response were all superior to those of pure PLLA scaffold.It’s worth noting that the percentage of skin tissue was regenerated by 95%within 14 days,which suggests the potential application for electrospun-based synthetic fibrous scaffolds on wound healing.

High-refractive index acrylate polymers for applications in nanoimprint lithography

The development of polymeric optical materials with a higher refractive index,transparency in the visible spectrum region and easier processability is increasingly desirable for advanced optical applications such as microlenses,image sensors,and organic light-emitting diodes.Most acrylates have a low refractive index(around 1.50)which does not meet the high perfo rmance requirements of advanced optical materials.In this research,three novel acrylates were synthesized via a facile one-step approach and used to fabricate optical transparent polymers.All of the polymers reveal good optical properties including high transparency(≥90%)in the visible spectrum region and high refractive index values(1.6363)at 550 nm.Moreover,nanostructures of these acrylate polymers with various feature sizes including nanogratings and photonic crystals were successfully fabricated using nanoimprint lithography.These results indicate that these acrylates can be used in a wide range of optical and optoelectronic devices where nanopatterned films with high refractive index and transparency are required.

Subvoxel light-sheet microscopy for high-resolution high-throughput volumetric imaging of large biomedical specimens

A key challenge when imaging whole biomedical specimens is how to quickly obtain massive cellular information over a large field of view(FOV).We report a subvoxel light-sheet microscopy(SLSM)method enabling high-throughput volumetric imaging of mesoscale specimens at cellular resolution.A nonaxial,continuous scanning strategy is developed to rapidly acquire a stack of large-FOV images with three-dimensional(3-D)nanoscale shifts encoded.Then,by adopting a subvoxel-resolving procedure,the SLSM method models these low-resolution,cross-correlated images in the spatial domain and can iteratively recover a 3-D image with improved resolution throughout the sample.This technique can surpass the optical limit of a conventional light-sheet microscope by more than three times,with high acquisition speeds of gigavoxels per minute.By fast reconstruction of 3-D cultured cells,intact organs,and live embryos,SLSM method presents a convenient way to circumvent the trade-off between mapping large-scale tissue(>100 mm3)and observing single cell(∼1-μm resolution).It also eliminates the need of complicated mechanical stitching or modulated illumination,using a simple light-sheet setup and fast graphics processing unit-based computation to achieve high-throughput,high-resolution 3-D microscopy,which could be tailored for a wide range of biomedical applications in pathology,histology,neuroscience,etc.

Soil bacterial communities interact with silicon fraction transformation and promote rice yield after long-term straw return

Returning crop straw into the soil is an important practice to balance biogenic and bioavailable silicon(Si)pool in paddy,which is crucial for the healthy growth of rice.However,owing to little knowledge about soil microbial communities responsible for straw degradation,how straw return affects Si bioavailability,its uptake,and rice yield remains elusive.Herein,we investigate the change of soil Si fractions and microbial community in a 39-year-old paddy field amended by a long-term straw return.Results show that rice straw return significantly increased soil bioavailable Si and rice yield from 29.9%to 61.6%and from 14.5%to 23.6%,respectively,when compared to NPK fertilization alone.Straw return significantly altered soil microbial community abundance.Acidobacteria was positively and significantly related to amorphous Si,while Rokubacteria at phylum level,Deltaproteobacteria,and Holophagae at class level was negatively and significantly related to organic matter adsorbed and Fe/Mn-oxide-combined Si in soils.Redundancy analysis of their correlations further demonstrated that Si status significantly explained 12%of soil bacterial community variation.These findings suggest that soil bacteria community and diversity interact with Si mobility by altering its transformation,thus resulting in the balance of various nutrient sources to drive biological Si cycle in agroecosystem.

Molecular analysis of cell-free DNA identifies distinct molecular features in patients with chemosensitive and chemorefractory small cell lung cancer

Dear Editor,Lung cancer is the predominant cause of cancer-related death worldwide[1].Non-small cell lung cancer accounts for 80%-85%and small cell lung cancer(SCLC)accounts for 15%-20%of all lung cancer cases[2].Patients with SCLC,a highly aggressive and poorly differentiated malignancy,have an alarming average 5-year overall sur-vival rate of less than 10%[3].Most patients with SCLC already show clinically detectable metastases at diag-nosis and have extremely poor prognoses,even when treated with multimodality therapy[4].Before the addi-tion of atezolizumab to chemotherapy became the first-line treatment of extensive-stage SCLC,chemotherapy is the primary treatment of SCLC[5].

Binary phase solid-state photopolymerization of acrylates： design, characterization and biomineralization of 3D scaffolds for tissue engineering

Porous polymer scaffolds designed by the cryogel method are attractive materials for a range of tissue engineering applications. However, the use of toxic cross- linker for retaining the pore structure limits their clinical applications. In this research, acrylates （HEA/PEGDA, HEMA/PEGDA and PEGDA） were used in the low-temperature solid-state photopolymerization to produce porous scaffolds with good structural retention. The morphology, pore diameter, mineral deposition and water absorption of the scaffold were characterized by SEM and water absorption test respectively. Elemental analysis and cytotoxicity of the biomineralized scaffold were revealed by using XRD and MTT assay test. The PEGDA-derived scaffold showed good water absorption ability and a higher degree of porosity with larger pore size compared to others. XRD patterns and IR results confirmed the formation of hydroxyapatite crystals from an alternative socking process. The overall cell proliferation was excellent, where PEGDA-derived scaffold had the highest and the most uniform cell growth, while HEMAJPEGDA scaffold showed the least. These results suggest that the cell proliferation and adhesion are directly proportional to the pore size, the shape and the porosity of scaffolds.

Schwarz lemma from a Kähler manifold into a complex Finsler manifold

Suppose that M is a complete Kähler manifold such that its holomorphic sectional curvature is bounded from below by a constant and its radial sectional curvature is also bounded from below.Suppose that N is a strongly pseudoconvex complex Finsler manifold such that its holomorphic sectional curvature is bounded from above by a negative constant.In this paper,we establish a Schwarz lemma for holomorphic mappings f from M into N.As applications,we obtain a Liouville type rigidity result for holomorphic mappings f from M into N,as well as a rigidity theorem for bimeromorphic mappings from a compact complex manifold into a compact complex Finsler manifold.