帕博利珠单抗治疗晚期非小细胞肺癌安全性和有效性的真实世界研究

背景与目的帕博利珠单抗(Pembrolizumab,PEM)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)在临床试验中被证实有效,但这些试验是基于按照特定标准筛选的患者群体,因此这些结果是否能够代表真实世界中患者的普遍情况,仍然值得讨论。本研究旨在基于真实世界数据评估PEM治疗晚期NSCLC的有效性和安全性。方法回顾性收集接受PEM治疗的晚期NSCLC患者的真实世界数据,使用倾向性评分匹配消除组间差异,评估PEM与化疗的有效性和安全性。结果在倾向性评分匹配后的450例患者中PEM组和化疗组任何等级不良事件发生率分别为79.87%和86.71%,≥3级不良事件发生率分别为4.03%和7.31%。PEM组和化疗组的客观缓解率分别为48.63%和36.00%(P=0.011),中位无进展生存期分别为15.5和8.8个月(P<0.001),中位总生存期分别为未达到和26.2个月(P<0.001)。结论PEM治疗晚期NSCLC在实际临床应用中显示出较好的生存率和可接受的安全性。

基于癸二酸二异辛酯的环保型复合缓蚀剂对钢筋的缓蚀效应

应用缓蚀剂控制混凝土中钢筋的腐蚀具有高效、廉价和易操作等优点,越来越受腐蚀研究者的关注。近年来,对环保型缓蚀剂的需求日益增加。因此,本工作发展了由癸二酸二异辛酯、D-葡萄糖酸钠和硫酸锌组成的环保型复合缓蚀剂并应用电化学测试技术和表面分析方法研究其对钢筋的缓蚀作用。结果表明,Q235钢筋在pH为11.00,含0.5 mol·L^(−1) NaCl的模拟污染的混凝土孔隙液中处于活化状态并发生局部腐蚀。含有59 mmol·L^(−1)癸二酸二异辛酯,0.5 mmol·L^(−1) D葡萄糖酸钠和1.5 mmol·L^(−1)硫酸锌组成的复合缓蚀剂对钢筋具有良好的协同缓蚀效应,在模拟污染混凝土孔隙液中和水泥砂浆试样中对钢筋的缓蚀效率分别达到96.8%和90.0%。该复合缓蚀剂是一种混合型缓蚀剂,对钢筋腐蚀的阴极反应和阳极反应均有抑制作用。

Optimal central venous pressure during partial hepatectomy for hepatocellular carcinoma

BACKGROUND:Low central venous pressure(CVP) affects hemodynamic stability and tissue perfusion.This prospective study aimed to evaluate the optimal CVP during partial hepatectomy for hepatocellular carcinoma(HCC).METHODS:Ninety-seven patients who underwent partial hepatectomy for HCC had their CVP controlled at a level of 0 to 5 mmHg during hepatic parenchymal transection.The systolic blood pressure(SBP) was maintained,if possible,at 90 mmHg or higher.Hepatitis B surface antigen was positive in 90 patients(92.8%) and cirrhosis in 84 patients(86.6%).Pringle maneuver was used routinely in these patients with clamp/unclamp cycles of 15/5 minutes.The average clamp time was 21.4±8.0 minutes.These patients were divided into 5 groups based on the CVP:group A:0-1 mmHg;B:1.1-2 mmHg;C:2.1-3 mmHg;D:3.1-4 mmHg and E:4.1-5 mmHg.The blood loss per transection area during hepatic parenchymal transection and the arterial blood gas before and after liver transection were analyzed.RESULTS:With active fluid load,a constant SBP ≥90 mmHg which was considered as optimal was maintained in 18.6% in group A(95% CI:10.8%-26.3%);39.2% in group B(95% CI:29.5%-48.9%);72.2% in group C(95% CI:63.2%-81.1%);89.7% in group D(95% CI:83.6%-95.7%);and 100% in group E(95% CI:100%-100%).The blood loss per transection area during hepatic parenchymal transection decreased with a decrease in CVP.Compared to groups D and E,blood loss in groups A,B and C was significantly less(analysis of variance test,P【0.05).Compared with the baseline,the blood oxygenation decreased significantly when the CVP was reduced.Base excess and HCO 3-in groups A and B were significantly decreased compared with those in groups C,D and E(P【0.05).CONCLUSION:In consideration of blood loss,SBP,base excess and HCO 3-,a CVP of 2.1-3 mmHg was optimal in patients undergoing partial hepatectomy for HCC.

Polymorphism of OAS2 rs739901 C/A Involves the Susceptibility to EV71 Infection in Chinese Children

This study aimed to assess the relationship of OAS2 rs739901 5＇-flanking C/A polymorphisms with the susceptibility to Enterovirus-71 （EV71） infection. We investigated 294 hand-foot-mouth disease （HFMD） Chinese children with EV71 infection （165 mild cases and 129 encephalitis cases）. The improved multiplex ligation detection reaction （iMLDR） technique was used to test the genotypes. In EV71-infected patients, the CA genotype distribution （P=0.007）, A allele frequency （OR 1.32, 95% CI 1.0-1.7, P=0.034） and CA＋AA carriage frequency （P=0.003） of OAS2 rs739901 5＇-flanking were obviously elevated as compared with controls, but there were no statistically significant differences between mild cases and encephalitis cases. In EV71-infected patients, the counts of white blood cells （P=0.034） and blood glucose concentrations （P=0.042） were raised in A carriers （CA＋AA）. Among different genotypes of encephalitis cases, the contents of cerebrospinal fluid （CSF） showed no significant differences. IFN-7 levels in EV71-infected patients were higher than those in controls （mild group vs. control group, P〈0.01; encephalitis group vs. control group, P〈0.001）. In encephalitis cases, IFN-7 levels were reduced （P〈0.05） in A carriers compared to CC genotype, however, there were no significant differences between genotypes CA and AA （ P=0.226）. These findings suggest that OAS2 rs739901 5＇-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection, and A allele might be a risk factor of the susceptibility to EV-71 infection.

Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma

BACKGROUND The role of tumor-infiltrating lymphocytes(TILs)in the growth and progression of hepatocellular carcinoma(HCC)has attracted widespread attention.AIM To evaluate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for massive HCC by exploring the role of TIL in the tumor microenvironment.METHODS Fifteen massive HCC patients who underwent ALPPS treatment and 46 who underwent hemi-hepatectomy were selected for this study.Propensity score matching was utilized to match patients in ALPPS and hemi-hepatectomy groups(1:1).Quantitative analysis of TILs in tumor and adjacent tissues between the two groups was performed by immunofluorescence staining and further analyses with oncological characteristics.In the meantime,trends of TILs in peripheral blood RESULTS Continuous measurement of tumor volume and necrosis volume showed that the proportion of tumor necrosis volume on the seventh day after stage-I ALPPS was significantly higher than the pre-operative value(P=0.024).In the preoperative period of stage-I ALPPS,the proportion of tumor necrosis volume in the high CD8+T cell infiltration group was significantly higher than that in the low group(P=0.048).CONCLUSION TIL infiltration level maintained a dynamic balance during the preoperative period of ALPPS.Compared with right hemi-hepatectomy,the ALPPS procedure does not cause severe immunosuppression with the decrease in TIL infiltration and pathological changes in immune components of peripheral blood.Our results suggested that ALPPS is safe and feasible for treating massive HCC from the perspective of immunology.In addition,high CD8+T cell infiltration is associated with increasing tumor necrosis in the perioperative period of ALPPS.

CD4^(+)CD25^(+) regulatory T cells decreased future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy

BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned stage 2 ALPPS is future liver remnant(FLR)volume growth,but the exact mechanism has not been elucidated.The correlation between regulatory T cells(Tregs)and postoperative FLR regeneration has not been reported.AIM To investigate the effect of CD4^(+)CD25^(+)Tregs on FLR regeneration after ALPPS.METHODS Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS.Flow cytometry was performed to detect changes in the proportion of CD4^(+)CD25^(+)Tregs to CD4^(+)T cells in peripheral blood before and after ALPPS.To analyze the relationship between peripheral blood CD4^(+)CD25^(+)Treg proportion and clinicopathological information and liver volume.RESULTS The postoperative CD4^(+)CD25^(+)Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume,proliferation rate,and kinetic growth rate(KGR)of the FLR after stage 1 ALPPS.Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion(P=0.006);patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion(P=0.043).The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume,proliferation rate,and KGR were all greater than 0.70.CONCLUSION CD4^(+)CD25^(+)Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients’livers.Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.

Determination of Harmful Elements and Analysis of Pollution Level in Lysimachia christinae

[Objectives]To detect content of Pb,Cd,Hg,As,Cu,Zn,and Cr in Lysimachia christinae,and to analyze the pollution level.[Methods]Seven kinds of elements in L.christinae were determined by Inductively coupled plasma mass spectrometry and analyzed by single index and comprehensive index.[Results]The seven heavy metal elements showed good linearity in their respective concentration ranges.The recoveries of the samples were 84.5%-109.5%,and the RSD values were 2.30%-5.10%.Comparing the measured results of heavy metal elements with the limit values stipulated in the 2020 edition of the Chinese Pharmacopoeia and other standards,the Cr element in 19 batches of samples exceeded the standard,and the Zn element in 7 batches of samples exceeded the standard.The exceeding rates were 100.0%and 36.8%,respectively;the content of other heavy metal elements did not exceed the standard.The order of individual index from large to small was Cr,Zn,Cd,Hg,Cu,As,and Pb,and the average comprehensive pollution level was mild pollution and above.[Conclusions]L.christinae was mainly polluted by Cr,followed by Zn;this study can provide basic data for drafting of the limit standard for heavy metal elements in L.christinae.

Determining the efficacy of vitamin B12 mixed oral liquid in the treatment of radiation-induced esophagitis

Objective This study aimed to investigate the effects of vitamin B12 mixed oral liquid in the treatment of radiation-induced esophagitis in patients with esophageal cancer.Methods Seventy-five patients with esophageal cancer who met the enrollment criteria were randomly divided into the vitamin B12 mixed oral liquid group(39 patients in the study group)and the gentamicin mixed oral liquid group(36 patients in the control group).The effects of the two treatment methods on esophagitis grading,pain degree,body weight loss,and Karnofsky performance status(KPS)score in patients with radiation esophagitis were observed.Results In the control group,grade 1 radiation esophagitis accounted for 27.8%of the total patients,grade 2 accounted for 41.7%,and grades 3 and 4 accounted for 30.6%.In the vitamin B12 treatment group,grade 1 radiation esophagitis accounted for 66.7%of the total patients,grade 2 accounted for 25.6%,and grades 3 and 4 accounted for 7.7%;there was a significant difference between the vitamin B12 treatment group and control group(P<0.01).Similarly,pain caused by radiation esophagitis was significantly improved in the vitamin B12 group compared with the control group(P<0.05).After treatment,the average weight loss of the control group was(2.18±0.36)kg,while that of the vitamin B12 treatment group was(0.90±0.43)kg(P<0.05).The KPS scores of the vitamin B12 group were higher than those of the control group,which were 86.2±1.2 and 85.6±1.5,respectively,but there was no statistical difference(P>0.05).Conclusion Vitamin B12 mixed oral liquid can effectively reduce the severity of radiation esophagitis,relieve pain,improve patients’quality of life,and increase treatment compliance.

Plants affect the horizontal transmission of a new densovirus infecting the green peach aphid Myzus persicae by modulating honeydew production

In a tritrophic context of plant-insect-entomopathogen,plants play important roles in modulating the interaction of insects and their pathogenic viruses.Currently,the influence of plants on the transmission of insect viruses has been mainly studied on baculoviruses and some RNA viruses,whereas the impact of plants on other insect viruses is largely unknown.Here,we identified a new densovirus infecting the green peach aphid Myzus persicae and tested whether and how host plants influence the transmission of the aphid densovirus.The complete single-stranded DNA genome of the virus,M.persicae densovirus 2,is 5727 nt and contains inverted terminal repeats.Transcription and phylogenetic analysis indicated that the virus was distinct from other a few identified aphid densoviruses.The virus abundance was detected highly in the intestinal tract of aphids,compared with the lower level of it in other tissues including head,embryo,and epidermis.Cabbage and pepper plants had no obvious effect on the vertical transmission and saliva-mediated horizontal transmission of the virus.However,the honeydew-mediated horizontal transmission among aphids highly depended on host plants(65%on cabbages versus 17%on peppers).Although the virus concentration in the honeydew produced by aphids between 2 plants was similar,the honeydew production of the infected aphids reared on peppers was dramatically reduced.Taken together,our results provide evidence that plants influence the horizontal transmission of a new densovirus in an aphid population by modulating honeydew secretion of aphids,suggesting plants may manipulate the spread of an aphid-pathogenic densovirus in nature.

Teukolsky-like equations with various spins in spherically symmetric spacetime

We study wave equations with various spins on the background of a general spherically symmetric spacetime.We obtain the unified expression of the Teukolsky-like master equations and the corresponding radial equations with the general spins.We also discuss the gauge dependence in the gravitational-wave equations,which have appeared in previous studies.

130~170 GHz平坦毫米波噪声信号产生技术

本文提出了一种基于三束非相干光混频产生D波段平坦毫米波噪声信号的方法.通过设置与调节三束光的中心波长与滤波光谱宽度,利用高速光电探测器同时实现光生毫米波噪声信号的频率范围与功率谱平坦度有效可控.理论分析了三束高斯型非相干光的中心波长差、滤波光谱宽度与预设频段噪声功率谱平坦度的关系.实验中,以单行载流子光电探测器(UTC-PD)为光混频器,在130~170 GHz产生了超噪比(ENR)>35 dB、平坦度低至±2.5 dB的D波段毫米波噪声信号.

Deep learning for smart agriculture:Concepts,tools,applications,and opportunities

In recent years,Deep Learning(DL),such as the algorithms of Convolutional Neural Networks(CNN),Recurrent Neural Networks(RNN)and Generative Adversarial Networks(GAN),has been widely studied and applied in various fields including agriculture.Researchers in the fields of agriculture often use software frameworks without sufficiently examining the ideas and mechanisms of a technique.This article provides a concise summary of major DL algorithms,including concepts,limitations,implementation,training processes,and example codes,to help researchers in agriculture to gain a holistic picture of major DL techniques quickly.Research on DL applications in agriculture is summarized and analyzed,and future opportunities are discussed in this paper,which is expected to help researchers in agriculture to better understand DL algorithms and learn major DL techniques quickly,and further to facilitate data analysis,enhance related research in agriculture,and thus promote DL applications effectively.

Genetic evidence for asymmetric blocking of higher-order chromatin structure by CTCF/cohesin

Dear Editor,Similar to higher-order folding of polypeptide chains into functional proteins,linear DNA molecules are spatially folded in a hierarchical and dynamic manner into three-dimensional(3D)functional chromatin structures in eukaryotic nuclei(Huang and Wu,2016;Rowley and Corces,2018).This dynamic folding is closely related to many nuclear processes such as DNA replication and repair,chromosomal translo­cation,recombination,and segregation,as well as RNA transcription,splicing,and transport.In particular,dynamic long-distance chromatin looping interactions,which result in close spatial contacts between distal enhancers and target promoters,are thought to play a role in controlling precise spatiotemporal as well as cell-type specific gene expression during animal development(Rowley and Corces,2018).Mammalian genomes contain numerous noncoding regula­tory elements that regulate these dynamic long-distance chromatin looping interactions.

Automatic determination of optimal spectral peaks for classification of Chinese tea varieties using laser-induced breakdown spectroscopy

The accurate identification of tea varieties is of great significance to ensure the interests of tea producers and consumers.As a non-destructive or micro damage detection method,laser-induced breakdown spectroscopy(LIBS)has been widely used in the quality detection or classification of agricultural products and food.The objective of this research was to automatically select optimal spectral peaks from the full LIBS spectra,and develop effective classification model for identifying tea varieties.The LIBS spectra covering the region 200-500 nm were measured for 600 Chinese tea leaves including six varieties(i.e.Longjing green tea,Jinhao black tea,Tie Guanyin,Huang Jinya,White peony tea,and Anhua dark tea).A total of 50 optimal spectral peaks were automatically selected from full LIBS spectra(6102)by using the uninformative variable elimination(UVE)and partial least squares projection analysis,and the selected spectral peaks mainly represent the elemental difference in C,Fe,Mg,Mn,Al and Ca.Partial Least Squares Discriminant Analysis(PLS-DA)was used for developing classification model using selected optimal spectral peaks,and yielded the 99.77%classification accuracy for 300 test samples was reached.The results indicate that the proposed method can be used to identify leaf varieties in various tea products.

Ultrafast and real-time physical random bit extraction with all-optical quantization

Optical chaos generated by perturbing semiconductor lasers has been viewed,over recent decades,as an excellent entropy source for fast physical random bit generation(RBG)owing to its high bandwidth and large random fluctuations.However,most optical-chaos-based random bit generators perform their quantization process in the electrical domain using electrical analog-to-digital converters,so their real-time rates in a single channel are severely limited at the level of Gb/s due to the electronic bottleneck.Here,we propose and experimentally demonstrate an all-optical method for RBG where chaotic pulses are quantized into a physical random bit stream in the all-optical domain by means of a length of highly nonlinear fiber.In our proof-of-concept experiment,a 10-Gb/s random bit stream is successfully generated on-line using our method.Note that the single-channel real-time rate is limited only by the chaos bandwidth.Considering that the Kerr nonlinearity of silica fiber with an ultrafast response of few femtoseconds is exploited for composing the key part of quantizing laser chaos,this scheme thus may operate potentially at much higher real-time rates than 100 Gb/s provided that a chaotic entropy source of sufficient bandwidth is available.

Modulation format identification in fiber communications using single dynamical node-based photonic reservoir computing

We present a simple approach based on photonic reservoir computing(P-RC)for modulation format identification(MFI)in optical fiber communications.Here an optically injected semiconductor laser with self-delay feedback is trained with the representative features from the asynchronous amplitude histograms of modulation signals.Numerical simulations are conducted for three widely used modulation formats(on–off keying,differential phase-shift keying,and quadrature amplitude modulation)for various transmission situations where the optical signal-to-noise ratio varies from 12 to 26 d B,the chromatic dispersion varies from-500 to 500 ps/nm,and the differential group delay varies from 0 to 20 ps.Under these situations,final simulation results demonstrate that this technique can efficiently identify all those modulation formats with an accuracy of>95%after optimizing the control parameters of the P-RC layer such as the injection strength,feedback strength,bias current,and frequency detuning.The proposed technique utilizes very simple devices and thus offers a resource-efficient alternative approach to MFI.

Prediction of dissolved oxygen in a fishery pond based on gated recurrent unit (GRU)

Dissolved oxygen(DO),an important water quality indicator in aquaculture,affects the survival rate of aquatic creatures and the yield of aquatic production.Therefore,it is important to predict DO in fishery ponds for applying artificial aeration with low energy and cost.Recently,deep learning models,such as recurrent neural network(RNN),long short-term memory(LSTM),and gated recurrent unit(GRU),are often used to predict the trend of time series,but it is unclear which one of them is more suitable for prediction of DO in fishery ponds.In this work,the RNN model,LSTM model,and GRU model were used to build three DO predicting models.The performance of the three models were compared by mean absolute error(MAE),mean square error(MSE),mean absolute percentage error(MAPE),and the coefficient of determination(R2).The performance of RNN is worse result than LSTM and GRU.The four evaluation indicators of GRU are 0.450 mg/L,0.411,0.054,and 0.994,and the four indicators of LSTM are 0.407 mg/L,0.294,0.059,and 0.970,which shows that the performance of GRU is similar to LSTM,but the time cost and number of parameters used for GRU is much lower than LSTM.It is concluded that the GRU has overall better performance and can be applied to practical applications.

Automatic sweet pepper detection based on point cloud images using subtractive clustering

Automatic identification and detection of fruit on trees by machine vision is the basis of developing automatic harvesting robots in agriculture.The occlusion of branches,leaves and other fruits in canopy images will affect the accuracy of fruit detection.To provide a scientific and reliable technical guidance for fruit harvesting robots,a method using point cloud images was proposed in this study to detect red fruits to overcome the impact of occlusion on detection.Firstly,the fruit regions were segmented from a tree’s point cloud by applying the color threshold of red and green.Then,the noise in fruit point clouds was removed with sparse outlier removal.Finally,the point cloud of each fruit was detected and counted based on the subtractive clustering algorithm.For the sweet pepper dataset,the true positive rate(TPR)is 90.69%and the false positive rate(FPR)is 6.97%for all fruits that are at least partially visible in the scene.

A statistical analysis of the freshness of postharvest leafy vegetables with application of water based on chlorophyll fluorescence measurement

Vegetable freshness is very important for both restaurant and home consumers.In market,sellers frequently apply water to leafy vegetables to make them not lose weight and look fresh;however,these vegetables may not be stored for a long time as they appear.After a time limit,they may be quickly rotten.It is thus meaningful to investigate early and simple detection tools to measure leafy vegetable freshness while they are frequently applied water in selling.In this work,three types of newly harvested leafy vegetables were bought from a local farmer market and stored in the air with room temperature and roots submerging in water.Chlorophyll a fluorescence(ChlF)from the vegetables was measured each half a day for three days.The obtained ChlF data were analyzed statistically and the correlation of ChlF parameters and vegetable freshness/storage time was obtained.The k-mean classification was also performed.It is found that Fo,Fj,Fm/Fo,and Fv/Fm can be used as an early detection tool to differentiate the freshness of leafy vegetables on which water is constantly applied in storage without visible difference.

In-field automatic detection of maize tassels using computer vision

The heading stage of maize is an important period during its growth and development and indicates the beginning of its pollination.In this regard,an automated method for maize tassel detection is highly important to monitor maize growth.However,the recognition of maize heading stage mainly relies on visual evaluation.This method presents some limitations,such as expensive and subjective.This work proposed a novel method for automatic tassel detection.In the proposed algorithm,a color attenuation prior model was used to model the scene depth of saturation graph to remove image saturation.An Itti visual attention detection algorithm was used to detect the area of interest.Texture features and vegetation indices were used to develop a classification model to eliminate false positives.Pictures were captured using a commercial camera for two years to verify the stability of the proposed algorithm.Three indices were calculated to quantitatively assess and rate the algorithms.Experimental results show that the proposed method outperforms other existing methods,and its recall,precision,and F1 measure values are 86.30%,91.44%,and 88.36%,respectively.Results indicate that the proposed method can effectively detect maize tassels in field images and remain stable with time.