Efficacy comparison of fruquintinib,regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer

BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)CRC.Due to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than monotherapy.AIM To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical practice.METHODS A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally included.RESULTS A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)groups.The key clinical characteristics were well balanced among the groups.The median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,respectively.The median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 months.The FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with RP.No significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than R.FP has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical efficacy.Therefore,FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.

Contrast-induced ischemic colitis following coronary angiography:A case report

BACKGROUND Ischemic colitis(IC)is common,rising in incidence and associated with high mortality.Its presentation,disease behavior and severity vary widely,and there is significant heterogeneity in therapeutic strategies and prognosis.The common causes of IC include thromboembolism,hemodynamic insufficiency,iatrogenic factors and drug-induced.However,contrast-induced IC,especially isolated right colon ischemia is rarely reported.CASE SUMMARY A 52-year-old man was admitted to the hospital due to intermittent chest distress accompanied by palpitation.Coronary angiography was performed using 60 mL of the iodinated contrast agent iohexol(Omnipaque 300),and revealed moderate stenosis of the left anterior descending artery and right coronary artery.At 3 h post-procedure,he complained of epigastric pain without fever,diarrhea and vomiting.Vital signs remained normal.An iodixanol-enhanced abdominal computed tomography(CT)scan revealed thickening,edema of the ascending and right transverse colonic wall and inflammatory exudate,without thrombus in mesenteric arteries and veins.Following 4 days of treatment with antibiotic and supportive management,the patient had a quick and excellent recovery with disappearance of abdominal pain,normalization of leucocyte count and a significant decrease in C reactive protein.There was no recurrence of abdominal pain during the patient's two-year follow-up.CONCLUSION This case emphasizes that contrast-induced IC should be considered in the differential diagnosis of unexplained abdominal pain after a cardiovascular interventional procedure with the administration of contrast media.Timely imaging evaluation by CT and early diagnosis help to improve the prognosis of IC.

Review of Large Spacecraft Deployable Membrane Antenna Structures

The demand for large antennas in future space missions has increasingly stimulated the development of deployable membrane antenna structures owing to their light weight and small stowage volume. However, there is little literature providing a comprehensive review and comparison of different membrane antenna structures. Space-borne membrane antenna structures are mainly classified as either parabolic or planar membrane antenna structures. For parabolic membrane antenna structures, there are five deploying and forming methods, including inflation, inflation-rigidization, elastic ribs driven, Shape Memory Polymer （SMP）-inflation, and electrostatic form- ing. The development and detailed comparison of these five methods are presented. Then, properties of membrane materials （including polyester film and polyimide film） for parabolic membrane antennas are compared. Additionally, for planar membrane antenna structures, frame shapes have changed from circular to rectangular, and different ten- sioning systems have emerged successively, including single Miura-Natori, double, and multi-layer tensioning systems. Recent advances in structural configurations, tensioning system design, and dynamic analysis for planar membrane antenna structures are investigated. Finally, future trends for large space membrane antenna structures are pointed out and technical problems are proposed, including design and analysis of membrane structures,materials and processes, membrane packing, surface accuracy stability, and test and verification technology. Through a review of large deployable membrane antenna structures, guidance for space membrane-antenna research and applications is provided.

TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

Tripartite motif containing 22 (TRIM22), a member of the TRIM/RBCC family, has been reported to activate the nuclear factor-kappa B (NF-κB) pathway in unstimulated macrophage cell lines, but the detailed mechanisms governing this activation remains unclear. We investigated this mechanism in HEK293T cells. We found that overexpression of TRIM22 could activate the NF-κB pathway and conversely, could inhibit the tumor necrosis factor receptor-associated factor 6 (TRAF6)-stimulated NF-κB pathway in HEK293T cells. Further experiments showed that TRIM22 could decrease the self-ubiquitination of TRAF6, and interact with and degrade transforming growth factor-β activated kinase 1 binding protein 2 (TAB2), and that these effects could be partially rescued by a TRIM22 RING domain deletion mutant. Collectively, our data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-κB pathway by interacting with and degrading TAB2.

No expenditure difference among patients with liver cancer at stageⅠ-ⅣV:Findings from a multicenter cross-sectional study in China

Objective:The number of liver cancer patients in China accounts for more than half of the world.However,China currently lacks national,multicenter economic burden data,and meanwhile,measuring the differences among different subgroups will be informative to formulate corresponding policies in liver cancer control.Thus,the aim of the study was to measure the economic burden of liver cancer by various subgroups.Methods:A hospital-based,multicenter and cross-sectional survey was conducted during 2012・2014,covering 39 hospitals and 21 project sites in 13 provinces across China.The questionnaire covers clinical information,sociology,expenditure,and related variables.All expenditure data were reported in Chinese Yuan(CNY)using 2014 values.Results:A total of 2,223 liver cancer patients were enrolled,of whom 59.61%were late-stage cases(III-IV),and 53.8%were hepatocellular carcinoma.The average total expenditure per liver cancer patient was estimated as 53,220 CNY,including 48,612 CNY of medical expenditures(91.3%)and 4,608 CNY of non-medical expenditures(8.7%).The average total expenditures in stage I,H,m and stage IV were 52,817 CNY,50,877 CNY,50,678 CNY and 54,089 CNY(P>0.05),respectively.Non-medical expenditures including additional meals,additional nutrition care,transportation,accommodation and hired informal nursing were 1,453 CNY,839 CNY,946 CNY,679 CNY and 200 CNY,respectively.The one-year out-of-pocket expenditure of a newly diagnosed patient was 24,953 CNY,and 77.2%of the patients suffered an unmanageable financial burden.Multivariate analysis showed that overall expenditure differed in almost all subgroups(P<0.05),except for sex,clinical stage,and pathologic type.Conclusions:There was no difference in treatment expenditure for liver cancer patients at different clinical stages,which suggests that maintaining efforts on treatment efficacy improvement is important but not enough.To fiirtherly reduce the overall economic burden from liver cancer,more effort should be given to primary and secondary prevention strategies.

2021:A Year of Unprecedented Climate Extremes in Eastern Asia,North America,and Europe

The year 2021 was recorded as the 6th warmest since 1880.In addition to large-scale warming,2021 will be remembered for its unprecedented climate extremes.Here,a review of selected high-impact climate extremes in 2021,with a focus on China,along with an extension to extreme events in North America and Europe is presented.Nine extreme events that occurred in 2021 in China are highlighted,including a rapid transition from cold to warm extremes and sandstorms in spring,consecutive drought in South China and severe thunderstorms in eastern China in the first half of the year,extremely heavy rainfall over Henan Province and Hubei Province during summer,as well as heatwaves,persistent heavy rainfall,and a cold surge during fall.Potential links of extremes in China to four global-scale climate extremes and the underlying physical mechanisms are discussed here,providing insights to understand climate extremes from a global perspective.This serves as a reference for climate event attribution,process understanding,and high-resolution modeling of extreme events.

Down-regulation of HIV-1 Infection by Inhibition of the MAPK Signaling Pathway

The human immunodeficiency virus type 1(HIV-1) can interact with and exploit the host cellular machinery to replicate and propagate itself.Numerous studies have shown that the Mitogen-activated protein kinase(MAPK) signal pathway can positively regulate the replication of HIV-1,but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood.In this study,we used the Extracellular signal-regulated kinase(ERK) pathway inhibitor,PD98059,the Jun N-terminal kinase(JNK) pathway inhibitor,SP600125,and the p38 pathway inhibitor,SB203580,to investigate the roles of these pathways in HIV-1 replication.We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity.In addition,SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1 NL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity.We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059 when cells were treated with all three MAPK pathway inhibitors in combination.Finally,we show that HIV-1 virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.

Column adsorption of Cu(Ⅱ) by polymer-supported nano-iron oxides in the presence of sulfate: Experimental and mathematical modeling

Polymer-supported hydrous iron oxides(HFOs) are promising for heavy metals removal from aqueous systems.The ubiquitous inorganic ligands, e.g., sulfate, are expected to exert considerable impacts on pollutants removal by these hybrid sorbents. Herein, we obtained a hybrid sorbent HFO-PS by encapsulating nanosized HFO into macroporous polystyrene(PS) resin. Both batch and column sorption experiments of Cu(Ⅱ) by HFO-PS were carried out in the presence of sulfate. Obviously, the presence of sulfate is favorable for Cu(Ⅱ) sorption onto HFO-PS.The performances of column Cu(Ⅱ) removal were fitted and predicted with Adams–Bohart, Clark, Thomas and BDST models. Thomas model is suggested best-fit to predict the breakthrough curves. Besides, a linear correlation is observed between breakthrough time and column length based on BDST model, which might be useful for predicting the breakthrough time for Cu(Ⅱ) removal by HFO-PS.

Dual-Use Signal Design for Radar and Communication via Joint Orthogonal Signal and Phase Modulation

This paper proposes a new information modulation resorting to orthogonal signal and its phase for dual-function radar communication(DFRC)systems.Focusing on the standardized linear frequency modulation(LFM)signal by additional phase,a bank of signals enjoying satisfactory autocorrelation and cross-correlation characteristics,are generated.Then,these signals map the different information as well as their phases are also modulated to increase the communication bit rate,thus yielding a series of dual-use signals.Finally,the radar detection and communication performance of dual-use signals are also provided through numerical simulation and half-physical platform verification,confirming the effectiveness of the designed signals compared with the existing design strategy.

Effect of sulfate on Cu(Ⅱ)sorption to polymer-supported nano-hydrated ferric oxides:Experimental and modeling studies

Incorporating of hydrous ferric oxide(HFO)inside porous supports with large sizes has become an effective way to decontaminate the water from heavy metals.Ubiquitous anions like sulfate are usually present in high concentrations in water,and might greatly affect adsorption behavior of hybrid HFO.Here,a polymer-based HFO-CPS was fabricated by encapsulating nano-HFO inside a chloromethylated polystyrene polymer(CPS)and the reactivity of HFO-CPS with Cu(Ⅱ)was evaluated in the presence of sulfate ions.Surface complexation theory was firstly employed to describe the effect of sulfate on Cu(Ⅱ)adsorption edges of hybrid HFO-CPS,where constant capacitance model(CCM)was adopted.The available weak adsorption site Fe_((2))OH of hybrid HFO-CPS was found to decrease from 20% Fe to 5% Fe,which might be caused by the pore plugging effect after HFO encapsulation.With the assumption that a ternary complex was formed,the effect of sulfate on Cu(Ⅱ)adsorption by HFO-CPS were successfully described by CCM using the optimized Fe_((2))OH site under different sulfate concentrations(1 or 10 mmol·L^(-1))and Cu/Fe ratios(0.0042 or 0.0252).It is confirmed that the formation of FeOHCuSO4 ternary surface complexes played an important role in enhancing Cu(Ⅱ)adsorption on HFO-CPS in the presence of sulfate.

Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report

BACKGROUND QT interval prolongation can induce torsades de pointes(TdP),a potentially fatal ventricular arrhythmia.Recently,an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset.Moreover,recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome(LQTS)and TdP development.CASE SUMMARY A 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks.The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein.Once after a high fever,the patient suddenly lost consciousness,and electrocardiogram(ECG)showed transient TdP onset after frequent premature ventricular contraction.The patient recovered sinus rhythm and consciousness spontaneously,and post-TdP ECG revealed a prolonged QTc interval of 560 ms.The patient’s clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still’s disease(AOSD).There was no evidence of cardiac involvement.After the AOSD diagnosis,discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval.The genetic analysis identified that the patient and her father had heterozygous mutations in KCNH2(c.1370C>T)and AKAP9(c.7725A>C).During the 2-year follow-up period,the patient had no recurrence of any arrhythmia and maintained normal QTc interval.CONCLUSION This case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset.Genetic analysis should be considered to identify individuals at high risk of developing TdP.

农民选择养老保险行为的影响因素分析--基于CGSS调查数据

近年来,中国已步入老龄化社会,并且老龄化的情势逐年加剧。研究农户选择养老保险的意愿对于解决农村人口老龄化问题、建立全民社会保障体系有着重要意义。本文基于2017年中国人民大学中国调查与数据中心《中国综合社会调查》数据,运用二元Logistic模型对农民参与养老保险行为及影响因素进行了分析。实证分析结果表明,年龄、受教育程度、养儿防老观念和医疗保险参与情况对是否参与养老保险产生显著的正向影响关系;而地区会产生显著负向影响。

Preparation of(Lu,Y)_(3)(Al,Sc,Cr)_(2)Al_(3)O_(12)phosphor ceramics with high thermal stability for near-infrared LED/LD

Near-infrared(NIR)phosphor-converted light-emitting diodes/laser diodes(LEDs/LDs)are prospective lighting sources for NIR spectroscopy.However,developing NIR phosphor materials with desired thermal robustness and high photoelectric efficiency is a crucial challenge for their applications.In this work,based on the cationic radius matching effect,a series of(Lu,Y)_(3)(Al,Sc,Cr)_(2)Al_(3)O_(12)NIR phosphor ceramics(LuYScCr NIR-PCs)were fabricated by vacuum sintering.Excellent thermal stability(95%@150℃)was obtained in the prepared NIR-PCs,owing to their weak electron-phonon coupling effect(small Huang-Rhys factor).Being excited at 460 nm,NIR-PCs realized a broadband emission(650-850 nm)with internal quantum efficiency(IQE)of 60.68%.Combining NIR-PCs with LED/LD chips,the maximum output power of the encapsulated LED prototype was 447 mW@300 mA with photoelectric efficiency of as high as 18.6%@180 mA,and the maximum output power of the LD prototype was 814 mW@2.5 A.The working temperatures of NIR-PCs were 70.8℃@300 mA(LED)and 102.8℃@3 A(LD).Finally,the prepared NIR-PCs applied in food detection were verified in this study,demonstrating their anticipated application prospects in the future.

High Spicy Food Intake and Risk of Cancer： A Meta-analysis of Case-control Studies

Background：Studies on the association between spicy food intake and cancer risk have reported inconsistent results.We quantitatively assessed this association by conducting a meta-analysis based on evidence from case-control studies.Methods：PubMed,EMBASE,and the Cochrane Library were searched for eligible publications.Combined odds ratios （ORs） with their 95% confidence interval （CI） were calculated using a random-or fixed-effects model.The methodological quality of the included articles was assessed using the Newcastle-Ottawa scale （NOS）.All data were analyzed using STATA 1 1.0 software （version 11.0;StataCorp.,College Station,TX,USA）.Subgroup analyses were also performed with stratification by region,sex,number of cases,cancer subtype,source of the control group,and NOS score.Results：A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis （7884 patients with cancer and 10,142 controls）.Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 （95% CI =1.35-2.29） in spite of significant heterogeneity （P 〈 0.00l）.In the subgroup analyses,this positive correlation was still found for gastric cancer,different regions,different numbers of cases,different sources of the control group,and high-quality articles （NOS score of≥ 7）.However,no statistically significant association was observed for women,esophageal cancer,gallbladder cancer,or low-quality articles （NOS score of〈7）.No evidence of publication bias was found.Conclusions：Evidence from case-control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity.More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer.

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies

Until now,there has been a lack of standard and effective treatments for patients with recurrent malignant tumors or abdominal and pelvic malignancies with extensive invasion(Morris,2000).Generally,these patients face problems such as inability to undergo surgery or chemotherapy resistance(Combs et al.,2016).Re-radiotherapy has achieved a prominent place in the treatment of patients who have received radiotherapy previously and developed in-field recurrences(Straube et al.,2018).However,re-radiotherapy is very complicated,requiring comprehensive consideration of appropriate radiation dose,interval from first radiotherapy,boundary of the radiotherapy target area,and damage to surrounding normal tissues(Straube et al.,2019).In other words,it is necessary to focus on the protection of surrounding normal tissues while maximizing the eflFicacy of re-radiotherapy in such patients.

Dgcr8 deletion in the primitive heart uncovered novel microRNA regulating the balance of cardiac-vascular gene program

Primitive mammalian heart transforms from a single tube to a four-chambered muscular organ during a short developmental window.We found that knocking out global microRNA by deleting Dgcr8 microprocessor in Mespl cardiovascular progenitor cells lead to the formation of extremely dilated and enlarged heart due to defective cardiomyocyte(CM)differentiation.Transcriptome analysis revealed unusual upregulation of vascular gene expression in Dgcr8 cKO hearts.Single cell RNA sequencing study further confirmed the increase of angiogenesis genes in single Dgcr8 cKO CM.We also performed global microRNA profiling of E9.5 heart for the first time,and identified that miR-541 was transiently highly expressed in E9.5 hearts.Interestingly,introducing miR-541 back into microRNA-free CMs partially rescued their defects,downregulated angiogenesis genes and significantly upregulated cardiac genes.Moreover,miR-541 can target Ctgf and inhibit endothelial function.Our results suggest that micro-RNAs are required to suppress abnormal angiogenesis gene program to maintain CM differentiation.

Ion therapy of pulmonary fibrosis by inhalation of ionic solution derived from silicate bioceramics

Pulmonary fibrosis(PF)is a chronic and progressively fatal disease,but clinically available therapeutic drugs are limited due to efficacy and side effects.The possible mechanism of pulmonary fibrosis includes the damage of alveolar epithelial cells II(AEC2),and activation of immune cells such as macrophages.The ions released from bioceramics have shown the activity in stimulating soft tissue derived cells such as fibroblasts,endothelia cells and epithelia cells,and regulating macrophage polarization.Therefore,this study proposes an“ion therapy”approach based on the active ions of bioceramic materials,and investigates the therapeutic effect of bioactive ions derived from calcium silicate(CS)bioceramics on mouse models of pulmonary fibrosis.We demonstrate that silicate ions significantly reduce pulmonary fibrosis by simultaneously regulating the functions of AEC2 and macrophages.This result suggests potential clinical applications of ion therapy for lung fibrosis.

Design and analysis of a novel hinged boom based on cable drive

Hinged booms are widely used in astrophysics missions;however,the trajectory and deployment velocity are difficult to control because they are usually driven by springs,which limits their application in narrow spaces.Thus,a novel hinged boom is highly required to achieve motion controllability.Through an equivalent substitution between the cable drive loop and the binary link in topology,a type synthesis method for the cable-driven single-degree-of-freedom chain is proposed based on the single-open-chain(SOC)adding method.According to the configuration design,a novel cable-driven hinged boom is proposed,aiming to achieve boom synchronism.Then,to preload easily,a method that preload is applied and measured at the cable ends is adopted and the relationship between the initial preload and the target preload is deduced.By analyzing the distribution of cable tension,a new stiffness model is proposed thus a stiffness equation is obtained.Finally,the dynamic simulation analysis and zero-gravity deployment experiment of the hinged boom is carried out to verify its reliability.This research provides a new way for the type synthesis of cable-driven single-degree-of-freedom chain and a new model for analyzing cable-driven stiffness.Moreover,the novel cable-driven hinged boom obtained in this study can be well-applied in the field of aerospace.

Structural covariance network of the hippocampus–amygdala complex in medication-nale patients with first-episode major depressive disorder

Background The hippocampus and amygdala are densely interconnected structures that work together in multiple affective and cognitive processes that are important to the etiology of major depressive disorder(MDD).Each of these structures consists of several heterogeneous subfields.We aim to explore the topologic properties of the volume-based intrinsic network within the hippocampus–amygdala complex in medication-nale patients with first-episode MDD.Methods High-resolution T1-weighted magnetic resonance imaging scans were acquired from 123 first-episode,medication-nale,and noncomorbid MDD patients and 81 age-,sex-,and education level-matched healthy control participants(HCs).The structural covariance network(SCN)was constructed for each group using the volumes of the hippocampal subfields and amygdala subregions;the weights of the edges were defined by the partial correlation coefficients between each pair of subfields/subregions,controlled for age,sex,education level,and intracranial volume.The global and nodal graphmetrics were calculated and compared between groups.Results Compared with HCs,the SCN within the hippocampus–amygdala complex in patients with MDD showed a shortened mean characteristic path length,reduced modularity,and reduced small-worldness index.At the nodal level,the left hippocampal tail showed increased measures of centrality,segregation,and integration,while nodes in the left amygdala showed decreased measures of centrality,segregation,and integration in patients with MDD compared with HCs.Conclusion Our results provide the first evidence of atypical topologic characteristics within the hippocampus–amygdala complex in patients with MDD using structure network analysis.It provides more delineate mechanism of those two structures that underlying neuropathologic process in MDD.