Fe_(3)O_(4)纳米粒子的制备及载药释放性能研究

采用改进的Hummers法获得氧化石墨烯(GO),通过共沉淀法制备了GO与磁性Fe_(3)O_(4)纳米粒子结合的GO/Fe_(3)O_(4)复合材料,分析了复合材料的晶体结构、微观形貌、磁化性能和载药性能,研究结果表明:GO/Fe_(3)O_(4)复合材料具有较高的结晶度,GO掺杂改善了Fe_(3)O_(4)颗粒的均匀度,晶粒尺寸为13~15 nm。GO/Fe_(3)O_(4)复合材料表现出超顺磁性,饱和磁化强度有轻微降低。利用GO/Fe_(3)O_(4)负载阿霉素(DOX)研究了载药释放性能,GO/Fe_(3)O_(4)/DOX包合物的DOX包封率均值为62.24%,具有较高的包封率,药物释放具有一定的pH依赖性,在pH=7.4时,GO/Fe_(3)O_(4)的累计释放率在75 h达到73.3%,摄入试验测试表明GO/Fe_(3)O_(4)载体具有一定的靶向性,在生物医学领域有广阔的应用前景。

A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F

As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear.Using the electron microscopy technology,along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays,we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells,accompanied by an increased total level of triglycerides.At the molecular level,the lipogenesis-associated mRNAs and proteins,including acetyl-CoA carboxylase,fatty acid synthase,stearoyl-CoA desaturase-1,peroxisome proliferator-activated receptor gamma,and CCAAT-enhancer-binding proteins,increased significantly via the AMP-activated protein kinase(AMPK)-mammalian target of rapamycin(mTOR)signaling regulation in both in vitro and in vivo studies.Furthermore,the immunofluorescence results also showed the robust lipogenesis induced by BPF,evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei.To investigate the intervention strategies for BPF-induced NAFLD-like changes,we demonstrated that bellidifolin,isolated and purified from Swertia chirayita,significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins.Therefore,the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells,while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.

Expert Recommendation in Community Question Answering via Heterogeneous Content Network Embedding

ExpertRecommendation(ER)aims to identify domain experts with high expertise and willingness to provide answers to questions in Community Question Answering(CQA)web services.How to model questions and users in the heterogeneous content network is critical to this task.Most traditional methods focus on modeling questions and users based on the textual content left in the community while ignoring the structural properties of heterogeneous CQA networks and always suffering from textual data sparsity issues.Recent approaches take advantage of structural proximities between nodes and attempt to fuse the textual content of nodes for modeling.However,they often fail to distinguish the nodes’personalized preferences and only consider the textual content of a part of the nodes in network embedding learning,while ignoring the semantic relevance of nodes.In this paper,we propose a novel framework that jointly considers the structural proximity relations and textual semantic relevance to model users and questions more comprehensively.Specifically,we learn topology-based embeddings through a hierarchical attentive network learning strategy,in which the proximity information and the personalized preference of nodes are encoded and preserved.Meanwhile,we utilize the node’s textual content and the text correlation between adjacent nodes to build the content-based embedding through a meta-context-aware skip-gram model.In addition,the user’s relative answer quality is incorporated to promote the ranking performance.Experimental results show that our proposed framework consistently and significantly outperforms the state-of-the-art baselines on three real-world datasets by taking the deep semantic understanding and structural feature learning together.The performance of the proposed work is analyzed in terms of MRR,P@K,and MAP and is proven to be more advanced than the existing methodologies.

立式驱动浅旋耙设计与参数优化

针对中国黄淮海地区保护性耕作少免耕作业、表土耕作时对地表平整度、表层碎土效果要求较高的特点。研究设计了一种立式驱动浅旋耙,通过对由作业机构参数进行设计优化、刀具的运动学分析与动力学分析,得出了影响土壤受力的因素为机具前进速度与刀具转速,并采用离散元仿真分析对影响因素进行进一步分析。通过田间验证试验,以碎土率、土壤容重、地表平整度为试验指标,对立式驱动浅旋耙进行性能优化试验。结果表明:在前进速度为 1.4 m/s,刀具转速为 350 r/min 时,其碎土率为 95.4%,土壤容重为 0.82 g/cm^3,土壤平整度为 16.3 mm,满足少免耕作业前碎土及秸秆覆盖要求。该研究为少免耕播种前的地表浅旋作业机具提供了参考。

Changes in Mean and Extreme Temperature and Precipitation over the Arid Region of Northwestern China： Observation and Projection

This paper reports a comprehensive study on the observed and projected spatiotemporal changes in mean and extreme climate over the arid region of northwestern China, based on gridded observation data and CMIP5 simulations under the RCP4.5 and RCP8.5 scenarios. The observational results reveal an increase in annual mean temperature since 1961, largely attributable to the increase in minimum temperature. The annual mean precipitation also exhibits a significant increasing tendency. The precipitation amount in the most recent decade was greater than in any preceding decade since 1961. Seasonally, the greatest increase in temperature and precipitation appears in winter and in summer, respectively. Widespread significant changes in temperature-related extremes are consistent with warming, with decreases in cold extremes and increases in warm extremes. The warming of the coldest night is greater than that of the warmest day, and changes in cold and warm nights are more evident than for cold and warm days. Extreme precipitation and wet days exhibit an increasing trend, and the maximum number of consecutive dry days shows a tendency toward shorter duration. Multi-model ensemble mean projections indicate an overall continual increase in temperature and precipitation during the 21 st century. Decreases in cold extremes, increases in warm extremes, intensification of extreme precipitation, increases in wet days, and decreases in consecutive dry days, are expected under both emissions scenarios, with larger changes corresponding to stronger radiative forcing.

中国国家药品监督管理局批准安罗替尼用于经两种系统化疗后疾病进展的晚期非小细胞肺癌的治疗

背景2018年5月8日,中国国家药品监督管理局(National Medical Products Administration,NMPA)批准了小分子多靶点抗血管抑制剂盐酸安罗替尼,用于既往经过至少两种系统化疗后疾病进展的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的治疗。概要中国NMPA审查了一项随机双盲、安慰剂对照的III期临床试验,该临床试验的主要终点为总生存期(overall survival,OS)。试验共纳入437例患者随机分组(2∶1)接受安罗替尼(n=294)或安慰剂(n=143)治疗,每日1次,连服2周,停药1周。表皮生长因子受体(epidermal growth factor receptor,EGFR)基因敏感突变或间变性淋巴瘤激酶(activating anaplasticlymphomakinase,ALK)阳性的患者须经过NMPA已批准的药物治疗后出现疾病进展。安罗替尼为中国NMPA批准的用于治疗既往经过两种及以上系统化疗后疾病进展的晚期NSCLC患者的首个药物。安罗替尼组的中位OS(9.46个月)较安慰剂组[6.37个月;风险比(hazard ratio,HR)=0.70,95%置信区间(confidence Interval,CI):0.55–0.89;双侧log-rank P=0.002]显著延长。安罗替尼组的客观缓解率(objective responserate,ORR)为9.2%,安慰剂组为0.7%。安罗替尼组的中位缓解持续时间(durationofresponse,DoR)为4.83个月,95%CI为3.31–6.97个月。安罗替尼的常见不良反应(adverse drug reactions,ADRs)包括高血压(67.4%)、手足综合征(43.9%)、咳血(14.0%)、促甲状腺激素(thyroid stimulating hormone,TSH)升高(46.6%)、心电图QT间期(corrected QT Interval,QTc)延长(26.2%)。结论安罗替尼显著延长了患者的OS,可作为经二线及以上化疗后晚期或转移性非小细胞肺癌的一种新的治疗方案。

Martentoxin, a large-conductance Ca^(2+)-activated K^+ channel inhibitor, attenuated TNF-α-induced nitric oxide release by human umbilical vein endothelial cells

Martentoxin, a 4,046 Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch, has been demonstrated to block large-conductance Ca2＋-activated K＋ （BKca） channels; however, its biological roles are still largely unknown. In the present study, we investigated the pharmacological effects of martentoxin on regulating the production of nitric oxide induced by TNF-a in human umbilical vein endothelial cells （HU- VECs）. We found that, 1, 10 and 100 ~tmol/L martentoxin decreased nitric oxide production by HUVECs ex- posed to 10 ng/mL TNF for 6, 12 and 24 hours. We further demonstrated that martentoxin inhibited the activity of iNOS and retarded the down-regulation of eNOS mRNA induced by TNF-a. Therefore, martentoxin could be a potential therapeutic agent for vascular diseases.

Exploiting Geo-Social Correlations to Improve Pairwise Ranking for Point-of-Interest Recommendation

Recently, as location-based social network(LBSN) rapidly grow, point-of-interest(POI) recommendation has become an important way to help people locate interesting places. Nowadays, there have been deep studies conducted on the geographical and social influence in the point-of-interest recommendation model based on the rating prediction. The fact is, however, relying solely on the rating fails to reflect the user's preferences very accurately, because the users are most concerned with the list of ranked point-of-interests(POIs) on the actual output of recommender systems. In this paper, we propose a co-pairwise ranking model called Geo-Social Bayesian Personalized Ranking model(GSBPR), which is based on the pairwise ranking with the exploiting geo-social correlations by incorporating the method of ranking learning into the process of POI recommendation. In this model, we develop a novel BPR pairwise ranking assumption by injecting users' geo-social preference. Based on this assumption, the POI recommendation model is reformulated by a three-level joint pairwise ranking model. And the experimental results based on real datasets show that the proposed method in this paper enjoys better recommendation performance compared to other state-of-the-art POI recommendation models.

基于Au/rGO/FeOOH的新型电化学传感器一步检测亚硝酸盐

亚硝酸盐是一种广泛存在的原料,长期食用会对人体健康不利甚至致癌。因此,简单、灵敏的亚硝酸盐检测方法的开发具有非常重要的意义。本文合成了金/还原氧化石墨烯/羟基氧化铁(Au/rGO/FeOOH)复合材料,并通过SEM、XRD和EDX等测试进行了材料表征。将合成的复合材料滴涂在氧化氟锡(FTO)电极表面,利用它们的协同催化氧化性能,成功构建了一步检测亚硝酸盐(NO_(2)^(-))的新型电化学传感器。在最佳优化实验条件下,通过差分脉冲伏安法实现NO_(2)^(-)的定量检测,其线性范围为0.001~5mmol·L^(-1),检出限为0.8μmol·L^(-1)(S/N=3),且响应时间小于2s。同时,所制备的传感器表现出良好的选择性和重现性,也能用于实际样品的测定。

Detachment of esophageal carcinoma cells from extracellular matrix causes relocalization of death receptor 5 and apoptosis

AIM： To investigate the effect of detachment of esophageal cancer cells from extracellular matrix on the localization of death receptor 5 （DR5） and apoptosis. METHODS： Anchorage-dependent EC9706 cells of esophageal squamous cell carcinoma were pretreated or not treated with brefeldin A. Detached cells were harvested by ethylenediaminetetraacetic acid digestion. Expression and localization of DR5 in these cells were determined by immunocytochemical and immunofluorescence assays, as well as flow cytometry analysis. Apoptosis of EC9706 cells was detected by flow cytometry after stained with fluorescein isothiocyanate-labeled annexin V/propidium iodide. Activation of caspase 8 was detected by Western blot analysis. RESULTS： Immunocytochemical assay indicated that DR5 was predominantly perinuclear in adherent cells but was mainly localized in cell membrane in detached cells. In addition, immunofluorescence assay also confirmed the above-mentioned results, and further demonstrated that DR5 was present in the form of coarse granules in detached cells, but in the form of fine granules in adherent cells. Cytometry analysis revealed higher levels of DR5 expression on the surfaces of brefeldin-A-untreated cells than on the surfaces of brefeldin-A-treated cells, but brefeldin A treatment did not affect the total DR5 expression levels. Moreover, nocodazole did not influence the extracelluar DR5 expression levels in EC9706 cells. Apoptosis assay revealed that detached cells were more sensitive to DR5 antibody-induced apoptosis than adherent ceils. Western blotting showed that caspase 8 was activated in temporarily detached cells 4 h earlier than in adherent cells. CONCLUSION： Progress from adhesion to detachment of EC9706 cells causes DR5 relocalization, and promotes cytoplasmic translocation of DR5 to cell surfaces via a Golgi-dependent pathway. Moreover, it might also result in DR5 aggregation to render apoptosis of detached cells.

Characteristics of abrupt changes of snow cover and seasonal freeze-thaw layer in the Tibetan Plateau and their impacts on summer precipitation in China

In this paper, a variation series of snow cover and seasonal freeze-thaw layer from 1965 to 2004 on the Tibetan Plateau has been established by using the observation data from meteorological stations. The sliding T-test, M-K test and B-G algorithm are used to verify abrupt changes of snow cover and seasonal freeze-thaw layer in the Tibetan plateau. The results show that the snow cover has not undergone an abrupt change, but the seasonal freeze-thaw layer obviously witnessed a rapid degradation in 1987, with the frozen soil depth being reduced by about 15 cm. It is also found that when there ~s less snow in the plateau region, precipitation in South China and Southwest China increases. But when the frozen soil is deep, precipitation in most of China apparently decreases. Both snow cover and seasonal freeze-thaw layer on the plateau can be used to predict the summer precipitation in China. However, if the impacts of snow cover and seasonal freeze-thaw layer are used at the same time, the predictability of summer precipitation can be significantly improved. The significant correlation zone of snow is located in middle reaches of the Yangtze River covering the Hexi Corridor and northeastern Inner Mongolia, and the seasonal freeze-thaw layer exists in Mt. Nanling, northern Shannxi and northwestern part of North China. The significant correlation zone of simultaneous impacts of snow cover and seasonal freeze-thaw layer is larger than that of either snow cover or seasonal freeze-thaw layer. There are three significant correlation zones extending from north to south： the north zone spreads from Mr. Daxinganling to the Hexi Corridor, crossing northern Mt. Taihang and northern Shannxi; the central zone covers middle and lower reaches of the Yangtze River; and the south zone extends from Mt. Wuyi to Yunnan and Guizhou Plateau through Mt. Nanling.

Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model

AIM To investigate the effect of a single amino acid mutation in human class B scavenger receptor I(SR-BI) on the infectivity of cell culture-derived hepatitis C virus(HCVcc) in SR-BI knock-down Huh7-si SR-BI cells.METHODS Site-directed mutagenesis was used to construct the SR-BI S112 F mutation,and the mutation was confirmed by nucleotide sequencing. SR-BI knock-down Huh7-si SR-BI cells were transfected with SR-BI S112 F,SR-BI wild type(WT) and control plasmids,and then infected with HCVpp(HCV pseudoparticles) and hepatitis C virus derived from cell culture(HCVcc). A fluorescence assay was performed to analyze the effect of the S112 F mutation on HCV entry; quantitative real-time PCR,immunofluorescence,and Western blot assays were used to analyze the effect of the S112 F mutation on HCV infectivity. CHO cells expressing WT and SRBI S112 F were incubated with the HCV E2 protein expressed in HEK 293 T cells,and flow cytometry was performed to examine the ability of SR-BI S112 F to bind to the HCV E2 protein. Huh7-si SR-BI cells were transfected with SR-BI WT and the S112 F mutant,andthen Di I-HDL was added and images captured under the microscope to assess the ability of SR-BI S112 F to take up HDL.RESULTS The SR-BI S112 F mutation was successfully constructed. The S112 F mutation decreased the expression of the SR-BI m RNA and protein. SR-BI S112 F decreased HCV entry and HCVcc infectivity in Huh7-si SR-BI cells. The S112 F mutation impaired the binding of SR-BI to HCV E2 protein and decreased the HDL uptake of SR-BI.CONCLUSION The S112 F single amino acid mutation in SR-BI decreased the levels of the SR-BI m RNA and protein,as well as the ability of SR-BI to bind to the HCV E2 protein. Amino acid 112 in SR-BI plays important roles in HCV entry and the infectivity of HCVcc in vitro.

Impacts of snow cover and frozen soil in the Tibetan Plateau on summer precipitation in China

This paper presents an analysis of the mechanisms and impacts of snow cover and frozen soil in the Tibetan Plateau on the sum- mer precipitation in China, using RegCM3 version 3.1 model simulations. Comparisons of simulations vs. observations show that RegCM3 well captures these impacts. Results indicate that in a more-snow year with deep frozen soil there will be more precipita- tion in the Yangtze River Basin and central Northwest China, western Inner Mongolia, and Xinjiang, but less precipitation in Northeast China, North China, South China, and most of Southwest China. In a less-snow year with deep frozen soil, however, there will be more precipitation in Northeast China, North China, and southern South China, but less precipitation in the Yangtze River Basin and in northern South China. Such differences may be attributed to different combination patterns of melting snow and thawing frozen soil on the Plateau, which may change soil moisture as well as cause differences in energy absorption in the phase change processes of snow cover and frozen soil. These factors may produce more surface sensible heat in more-snow years when the fi＇ozen soil is deep than when the frozen soil is shallow. The higher surface sensible heat may lead to a stronger updraft over the Plateau, eventually contributing to a stronger South Asia High and West Pacific Subtropical High. Due to different values of the wind fields at 850 hPa, a convergence zone will form over the Yangtze River Basin, which may produce more summer pre- cipitation in the basin area but less precipitation in North China and South China. However, because soil moisture depends on ice content, in less-snow years with deep frozen soil, the soil moisture will be higher. The combination of higher frozen soil moisture with latent heat absorption in the phase change process may generate less surface sensible heat and consequently a weaker updraft motion over the Plateau. As a result, both the South Asia High and the West Pacific Subtropical High will be weaker, hence caus- ing more summer precipitation in northern China but less in southem China.

The pharmacological and toxicological action of strychnine on central nervous system

Strychnine is the main bioactive constituent responsible for the pharmacological and toxic properties of strychnos nux-vomica L.(Loganiaceae),which is known for severe neurotoxicity.Although its toxic threshold is easy to be reached and it is liable to cause poisoning,the effect of strychnine on the central nervous system(CNS)is crucial for its application in clinic.Therefore,the impacts of pharmacology and toxicology of strychnine on CNS have generated increasing interests.In this short review,we summarize the pharmacological activities,neurotoxicology,underlying mechanisms of the strychnine poisoning,and discuss the pharmacokinetics properties of strychnine.These findings could provide beneficial information for facilitating future mechanism research of neurotoxicity of strychnine and developing drugs to remedy neurotoxicity in the clinic.

Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and nephropathy.However,their activity in diabetic retinopathy(DR)remains unclear.Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR treatment.By single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic conditions.Treatment of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic mice.GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs.Additionally,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial DNA.Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes.Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling.This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Extreme characteristics and causes of the drought event in the whole Yangtze River Basin in the midsummer of 2022

Due to their huge socio-economic impacts and complex formation causes,extreme and continuous drought events have become the focus and nodus of research in recent years.In the midsummer(July-August)of 2022,a severe drought event occurred in the whole Yangtze River Basin(YRB),China.During that period,the precipitation in the upper,middle and lower reaches of the YRB dropped over 40%less than the 1961-2021 climatic mean,which had never happened previously.Furthermore,the temperature was the highest during 1961-2022.The record-breaking magnitude of less rainfall and high temperature directly led to the continuous development of this extreme drought event.An atmospheric moisture budget analysis revealed that the YRB midsummer rainfall anomaly was dominated by the anomalous powerful vertical moisture advection,which was derived from the strongest descending motion over the whole YRB in the 2022 midsummer during 1981-2022.The western Pacific subtropical high(WPSH)during the midsummer remained stronger,more westward and lasted longer than the climatic mean.As a result,the whole YRB was controlled by a positive geopotential height centre.Further evidence revealed that the anomalous subtropical zonal flow played a crucial role in inducing the extreme descent over the YRB.Moreover,the anomalous upper-tropospheric easterly flow over the YRB in 2022 is the strongest during 1981-2022,modulating the generation of the unprecedented descent anomaly over the YRB.The likelihood that an integrated connection of severe drought in East Asia and flood in West Asia and northwestern South Asia would increase when the extremely strong easterly anomalies in the upper troposphere emerged and induced descending adiabatic flow on the eastern sides of the Tibetan Plateau.The results of this study can provide scientific insights into the predictability of extreme drought events and provide ways to improve predictions.

俄罗斯税法典对受益所有人概念的引入和司法实践

在双边税收协定中,税收优惠应最大限度给予协定伙伴国存在最密切经济利益联系的居民企业,只有对所得享有独立支配权以及能决定未来经济命运的实际所得人才能够适用受益所有人概念,享受免税或低税率待遇。在国际税收方面,俄罗斯税务机关当前面临的主要问题就是避免双重征税协定的滥用以及不恰当地适用协定优惠,而受益所有人概念已成为俄罗斯打击滥用双重征税协定的主要手段。2015年1月1日,俄罗斯税法典引入受益所有人概念的规定正式生效。俄罗斯税法典的这一修订对我国国际税收领域也有一定的借鉴意义,同时也将促使中国投资者投资俄罗斯时需要慎重考量投资的商业架构。

China National Medical Products Administration approval summary:anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy

Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.

Construction and Application of a Climate Risk Index for China

In the context of global warming,China is facing with increasing climate risks.It is imperative to develop quantitative indices to reflect the climate risks caused by extreme weather/climate events and adverse climatic conditions in association with different industries.Based on the observations at 2288 meteorological stations in China and the meteorological disasters data,a set of indices are developed to measure climate risks due to water-logging,drought,high temperature,cryogenic freezing,and typhoon.A statistical method is then used to construct an overall climate risk index(CRI)for China from these individual indices.There is a good correspondence between these indices and historical climatic conditions.The CRI,the index of water-logging by rain,and the high temperature index increase at a rate of 0.28,0.37,and 0.65 per decade,respectively,from 1961 to 2016.The cryogenic freezing index is closely related to changes in the consumer price index for food.The high temperature index is correlated with the consumption of energy and electricity.The correlation between the yearly growth in claims on household property insurance and the sum of the water-logging index and the typhoon index in the same year is as high as 0.70.Both the growth rate of claims on agricultural insurance and the annual growth rate of hospital inpatients are positively correlated with the CRI.The year-on-year growth in the number of domestic tourists is significantly negatively correlated with the CRI in the same year.More efforts are needed to develop regional CRIs.

新型生物标志物可溶性髓样细胞触发受体-1在重症肺炎早期诊断中的应用价值

目的探究血清可溶性髓样细胞触发受体-1(sTREM-1)在重症肺炎早期诊断中的应用价值。方法2021年6月到2021年12月于吉林大学第二医院就诊的60例肺炎患者纳入研究组,其中重症40例(重症肺炎组)和轻症20例(普通肺炎组)。以及同期门诊体检者15例纳入健康对照组。研究组患者均于入院24 h内使用肺炎严重程度指数(PSI)评分进行评估;分别采用电化学发光法、散射比浊法、酶联免疫吸附实验(ELISA)检测血清降钙素原(PCT)、超敏C-反应蛋白(hs-CRP)和sTREM-1水平。比较重症肺炎组、普通肺炎组及健康对照组研究对象入组24 h内血清sTREM-1水平,并比较重症肺炎组和普通肺炎组研究对象入组24 h内血清PCT、hs-CRP水平及PSI评分。采用Pearson相关性分析探讨血清sTREM-1和hs-CRP水平与PSI评分的相关性;采用Spearson相关性探讨血清PCT水平与PSI评分的相关性。绘制受试者工作特征曲线(ROC)及应用MedCalc软件比较曲线下面积(AUC)比较血清sTREM-1、PCT和hs-CRP对重症肺炎早期诊断的价值。结果重症肺炎组、普通肺炎组以及健康对照组血清sTREM-1表达水平(4864.81±1314.53 pg/ml、1144.58±571.01 pg/ml、509.11±43.70 pg/ml)差异有统计学意义(F=109.292、P<0.001),其中重症肺炎组较普通肺炎组和健康对照组显著升高(t=10.981、P<0.001,t=9.264、P<0.001)。重症肺炎组患者血清PCT、hs-CRP水平以及PSI评分均高于普通肺炎组,差异有统计学意义(Z=-3.360、P=0.001,t=2.047、P=0.048,t=4.878、P<0.001)。血清sTREM-1、PCT和hs-CRP诊断重症肺炎的AUC分别为1.00、0.86和0.68(95%CI:1.00~1.00、0.73~0.98、0.51~0.86);分别以2916.92 pg/ml、0.31 ng/ml和32.14 mg/L为截断值时约登指数最大,对应的敏感性分别为100%、85%和85%,特异性分别为100%、81%和50%。sTREM-1诊断重症肺炎的AUC与hs-CRP、PCT差异均有统计学意义(Z=3.463、P<0.001,Z=2.220、P=0.026);hs-CRP与PCT差异无统计学意义(Z=1.454、P=0.146)。PSI评分与血清sTREM-1(r=0.641、P<0.001)、PCT(r=0.540、P=0.001)呈正相关,与血清hs-CRP无相关性(r=0.269、P=0.124)。结论肺炎患者血清sTREM-1升高,以重症患者升高更为显著,且其与PSI评分呈正相关;检测血清sTREM-1水平有助于早期诊断重症肺炎,且其特异性及敏感性高,均优于PCT和hs-CRP,有望成为新的早期诊断重症肺炎的生物标志物。