Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

Matrix-Mediated Color-Tunable Ultralong Organic Room Temperature Phosphorescence of 7H-Benzo[c]carbazole Derivatives

Building on the recent systematic research on 1Hbenzo[f]indole(Bd),an important advancement in constructing ultralong organic room temperature(UORTP)materials with a universal strategy via a readily obtained unit(7H-Benzo[c]carbazole,BCz)is proposed in this work.Pure powders of BCz and its derivatives merely exhibit blue fluorescence at ambient condition.However,when BCz and its derivatives are dispersed into polymer or powder matrixes,strong photo-activated green UORTP can be observed from their doped systems at room temperature.Moreover,the UORTP color can be tuned between green and yellow depending on the matrix.The ultralong phosphorescence originates from the generation of charge-separated states via radicals.The matrixes play a key role in both stabilizing charge-separated states and controlling UORTP color.More interestingly,when using polymethyl methacrylate as matrix,the doped films achieve stronger photo-activated ultralong phosphorescence underwater than in air at room temperature.Comparedwith Bd,BCz achieves better performance not only in ultralong phosphorescence properties but also in practical applications.This work gains a deeper insight into the mechanism of UORTP and paves a new approach to applying organic phosphorescent materials to underwater coating and imaging.

Fabrication and characterization of 3D printed biocomposite scaffolds based on PCL and zirconia nanoparticles

The application of three-dimensional printed polymer scaffolds in repairing bone defects is a promising strategy.Among them,polycaprolactone(PCL)scaffolds are widely studied due to their good processability and controlled degradation rate.However,as an alternative graft for repairing bone defects,PCL materials have poor hydrophilicity,which is not conducive to cell adhesion and growth.In addition,the poor mechanical properties of PCL materials cannot meet the strength required to repair bone defects.In this paper,nano-zirconium dioxide(ZrO2)powder is embedded in PCL material through a meltmixing process,and a regular grid scaffold is constructed by 3D printing.The embedding of nanometer zirconium dioxide powder improves the hydrophilicity and water absorption of the composite scaffold,which is conducive to cell adhesion,proliferation and growth and is beneficial to the exchange of nutrients.Therefore,the PCL/ZrO2 composite scaffold showed better biological activity in vitro.At the same time,the PCL/ZrO2 composite material system significantly improves the mechanical properties of the scaffold.Among them,compared with the pure PCL scaffold,the Young’s modulus is increased by about 0.4 times,and the compressive strength is increased by about 0.5 times.In addition,the osteogenic differentiation results also showed that the PCL/ZrO2 composite scaffold group showed better ALP activity and more effective bone mineralization than the pure PCL group.We believe that the 3D printed PCL/ZrO2 composite scaffold has certain application prospects in repairing bone defects.

Decay Rate for a Viscoelastic Equation with Strong Damping and Acoustic Boundary Conditions

This paper is concerned with a nonlinear viscoelastic equation with strong damping: . The objective of the present paper is to provide some results on the long-time behavior to this equation with acoustic boundary conditions. By using the assumptions on the relaxation function due to Tatar [1], we show an arbitrary rate of decay with not necessary of an exponential or polynomial one and without the assumption condition. The result extends and improves some results given in Cavalcanti [2].

Uniform Attractors for a Non-Autonomous Thermoviscoelastic Equation with Strong Damping

This paper considers the existence of uniform attractors for a non-autonomous thermoviscoelastic equation with strong damping in a bounded domain Ω&#8838;Rn(n≥1) by establishing the uniformly asymptotic compactness of the semi-process generated by the global solutions.

Efficacy,safety and pharmacokinetics of Unecritinib(TQ-B3101)for patients with ROS1 positive advanced non-small cell lung cancer:a Phase I/II Trial

This phase I/II trial characterized the tolerability,safety,and antitumor activities of unecritinib,a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1,ALK,and c-MET,in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer(NSCLC)harboring ROS1 rearrangements.Eligible patients received unecritinib 100,200.

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

适应免疫在肝炎 B 的控制起一个关键作用，这很好被接受病毒(HBV ) 感染。相反，天生的免疫的贡献仅仅在最近的年里收到了注意。像使用费的受体(TLR ) 察觉到联系病原体的分子模式并且激活抗病毒的机制，包括细胞内部的抗病毒的小径和抗病毒的受动器干扰素(IFN ) 和支持 inflammatory cytokines 的生产。从在 vitro 并且在 vivo 模型的试验性的结果证明了 TLR 调停细胞的发信号的小径和抗病毒的 cytokines 的生产的激活，导致 HBV 复制的抑制。然而， HBV 感染在主人房间和下游地表明小径的激活的封锁上与 TLR 表示的 downregulation 被联系。在主要 HBV 感染， TLR 可以减慢 HBV 感染，但是仅仅间接地作出贡献到病毒的清理。重要地， TLR 可以在 vivo 调制 HBV 特定的 T 房间和 B 房间回答，它为 HBV 感染的结束是必要的。因此， TLR 收缩筋正在答应候选人为长期的 HBV 感染的处理充当 immunomodulators。抗病毒的处理可以在长期的 HBV 感染恢复 TLR 表示和功能并且可以基于 TLR 激活增加治疗学的途径的功效。有抗病毒的治疗和 TLR 激活的联合治疗学的策略能便于 HBV 特定的有免疫力的回答的恢复并且从而，在长期地感染的 HBV 病人完成病毒的清理。

The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model

The outcome of hepatitis B viral(HBV)infection is determined by the complex interactions between replicating HBV and the immune system.While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively,the contribution of innate immune mechanisms remains to be defined.Here we examined the role of the interleukin-1 receptor/Toll-like receptor(IL-1R/TLR)signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model.Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice(WT)and a panel of mouse strains lacking specific innate immunity component expression.We found higher levels of HBV protein production and replication in Tlr2^(−/−),Tlr23479^(−/−),3d/Tlr24^(−/−),Myd88/Trif^(−/−)and Irak4^(−/−)mice,which was associated with reduced HBV-specific CD8+T-cell responses in these mice.Importantly,HBV clearance was delayed for more than 2 weeks in 3d/Tlr24^(−/−),Myd88/Trif^(−/−)and Irak4^(−/−)mice compared to WT mice.HBV-specific CD8+T-cell responses were functionally impaired for producing the cytokines IFN-γ,TNF-αand IL-2 in TLR signaling-deficient mice compared to WT mice.In conclusion,the IL-1R/TLR signaling pathway might contribute to controlling HBV infection by augmenting HBV-specific CD8+T-cell responses.

Clinical Characteristics of Hospitalized Patients with SARS-CoV-2 and Hepatitis B Virus Co-infection

Dear Editor,Coronavirus disease 2019(COVID-19)is a global pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2).SARS-Co V-2 infection was first detected in Wuhan,China in late December 2019.The virus was spreading rapidly to other cities of China and accumulating cases had been reported(Li et al.2020).

Tumor suppressor p53 functions as an essential antiviral molecule against Japanese encephalitis virus

Japanese encephalitis virus(JEV)is a mosquito-borne virus of the family Flaviviridae.It is the causative agent of Japanese encephalitis with approximately 50,000 infection cases and 10,000 fatal cases annually in Asia(Erlanger et al.,2009).Although liveattenuated JEV vaccine has been developed and used for human and pig vaccination,JE occurs epidemically or sporadically

Impact of Polymer Matrix on Polymer Mechanochromism from Excited State Intramolecular Proton Transfer

Mechanochromic polymers based on non-covalent changes have attracted much attention recently.Herein,we report the impact of inter/intramolecular hydrogen bonds on polymer mechanochromism from the excited state intramolecular proton transfer (ESIPT) process.PhMz-NH2-OH and PhMz=2A are designed and obtained by simple and high-yield synthesis,and are connected into polyurethane and poly(methyl acrylate-co-2-ethylhexyl acrylate),respectively.In the initial state,the PhMz-NH2-OH@PU sample shows blue fluorescence from the excited enol form (E*) excitons,owing to intermolecular hydrogen bonds that interrupt the ESIPT reactions but the PhMz=2A@PMA-2-EA sample expresses cyan fluorescence belonging to the excited keto form (K*) emission,implying that the intramolecular hydrogen bonds matter.Furthermore,under stretching,external force can tune the emission of the PhMz=2A@PMA-2-EA sample from K* to E* state.Though external force can putatively still promote a bond rotation,ESIPT reactions remain equivalently interrupted in both the relaxed and stressed states in a hydrogen-bond donating environment.DFT calculation confirms the force-induced increase in dihedral angle for the transition of ESIPT-on/off.Thus,PhMz-NH2-OH@PU and PhMz=2A@PMA-2-EA showed disparate initial ESIPT states and further different responses/sensitivity to force.This study reports a novel and efficient strategy for enriching mechanochromic investigation and extending the applications of ESIPT reactions.