Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

三维能量多普勒超声及血清FGFR4、Spondin-2对宫颈癌化疗疗效的评估价值

目的探讨三维能量多普勒超声(3D-PDU)及血清成纤维细胞生长因子受体4(FGFR4)、Spondin-2对顺铂联合氟尿嘧啶(PF)治疗宫颈癌的疗效评估价值。方法回顾性分析2017年7月—2019年7月攀枝花市妇幼保健院收治的98例宫颈癌患者临床资料,均采取PF治疗,根据化疗疗效分为有效组60例和无效组38例。比较有效组和无效组化疗前后3D-PDU参数[血管形成指数(VI)、血管形成-血流指数(VFI)、血流指数(FI)]、血清FGFR4、Spondin-2水平。Pearson法分析化疗前3D-PDU参数与血清FGFR4、Spondin-2水平的相关性。绘制受试者工作特征(ROC)曲线,分析化疗前3D-PDU参数及血清指标对化疗有效性的预测效能。结果①3D-PDU参数:化疗前两组FI、VFI、VI差异无统计学意义(P>0.05),化疗后两组FI、VFI、VI均较化疗前降低(P<0.05),化疗后有效组FI、VFI、VI低于无效组(P<0.05);②血清FGFR4、Spondin-2水平:化疗前两组血清FGFR4、Spondin-2水平差异无统计学意义(P>0.05),化疗后两组血清FGFR4、Spondin-2水平均较化疗前降低(P<0.05),化疗后有效组血清FGFR4、Spondin-2水平低于无效组(P<0.05);③相关性分析:化疗前PF治疗宫颈癌有效患者的VI、VFI、FI与血清FGFR4、Spondin-2水平呈正相关;④预测效能:ROC曲线显示化疗前联合预测宫颈癌化疗疗效的AUC最大,为0.854(95%CI:0.769,0.918),诊断敏感性和特异性分别为86.67%(95%CI:0.7486,0.9366)、76.32%(95%CI:0.5939,0.8797),其次为FGFR40.811(95%CI:0.719,0.883)、VFI 0.783(95%CI:0.688,0.860)、Spondin-20.782(95%CI:0.687,0.859)、FI 0.773(95%CI:0.677,0.851)、VI 0.758(95%CI:0.661,0.839)。结论化疗前宫颈癌3D-PDU参数与血清FGFR4、Spondin-2水平呈正相关,联合检测有助于预测化疗效果,为临床优化宫颈癌个体化治疗提供理论依据。

Increased interleukin-26 expression in proliferative diabetic retinopathy

AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPDR) group(n=20), proliferative diabetic retinopathy(PDR) group(n=20) and normal control group(n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay(ELISA). The m RNA change of IL-26 in peripheral blood mononuclear cells(PBMCs) was assessed by real-time polymerase chain reaction.RESULTS: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients(without antiVEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the m RNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the PBMCs.CONCLUSION: Protein and m RNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.

TiN/γ-Fe interface orientation relationship and formation mechanism of TiN precipitates in Mn18Cr2 steel

A Mn18Cr2 steel containing TiN precipitates was fabricated by vacuum induction melting.The morphology of TiN precipitates and the interface orientation relationship between TiN and γ-Fe were characterized by means of SEM,TEM and SAED,and the formation mechanism of TiN precipitates in Mn18Cr2 steel was clarified.Results show that the TiN precipitates are more likely to exhibit a cubic-shaped morphology and form both within the grain and at the grain boundary of γ-Fe.The interface orientation relationship between TiN and γ-Fe is determined as follows:(100)_(TiN)//■_(γ-Fe),■_(TiN)//■_(γ-Fe).Because of the smallest interfacialmisfit,the secondary close-packed lane {100} of TiN preferentially combines with the close-packed plane {111} of γ-Fe during the precipitation in order to minimize the interface energy.After nucleation,the TiN precipitates exhibit cubic appearance due to the fact that the TiN has a FCC structure with rock salt type structure.This study provides reference for the material design of the austenitic high-manganese steels with excellent yield strength.

Scanning the energy dissipation process of energetic materials based on excited state relaxation and vibration–vibration coupling

The energy dissipation mechanism of energetic materials（EMs） is very important for keeping safety. We choose nitrobenzene as a model of EM and employ transient absorption（TA） spectroscopy and time-resolved coherent anti-stokes Raman scattering（CARS） to clarify its energy dissipation mechanism. The TA data confirms that the excited nitrobenzene spends about 16 ps finishing the twist intramolecular charge transfer from benzene to nitro group, and dissipates its energy through the rapid vibration relaxation in the initial excited state. And then the dynamics of vibrational modes（VMs） in the ground state of nitrobenzene, which are located at 682 cm^-1（v1）, 854 cm^-1（v2）, 1006 cm^-1（v3）, and 1023 cm^-1（v4）,is scanned by CARS. It exhibits that the excess energy of nitrobenzene on the ground state would further dissipate through intramolecular vibrational redistribution based on the vibrational cooling of vi and v2 modes, v1 and v4 modes, and v3 and v4 modes. Moreover, the vibration-vibration coupling depends not only on the energy levels of VMs, but also on the spatial position of chemical bonds relative to the VM.

Regulation of a vacuolar proton-pumping P-ATPase MdPH5 by MdMYB73 and its role in malate accumulation and vacuolar acidification

As the main organic acid in fruits,malate is produced in the cytoplasm and is then transported into the vacuole.It accumulates by vacuolar proton pumps,transporters,and channels,affecting the taste and flavor of fruits.Among the three types of proton pumps(V-ATPases,V-PPases,and P-ATPases),the P-ATPases play an important role in the transport of malate into vacuoles.In this study,the transcriptome data,collected at different stages after blooming and during storage,were analyzed and the results demonstrated that the expression of MdPH5,a vacuolar proton-pumping P-ATPase,was associated with both pre-and post-harvest malate contents.Moreover,MdPH5 is localized at the tonoplast and regulates malate accumulation and vacuolar pH.In addition,MdMYB73,an upstream MYB transcription factor of MdPH5,directly binds to its promoter,thereby transcriptionally activating its expression and enhancing its activity.In this way,MdMYB73 can also affect malate accumulation and vacuolar pH.Overall,this study clarifies how MdMYB73 and MdPH5 act to regulate vacuolar malate transport systems,thereby affecting malate accumulation and vacuolar pH.

Charge transporting materials for perovskite solar cells

Perovskite solar cells(PSCs) have made great progress since 2009 and become the focus of current research. As an important part of PSCs, charge transporting materials play an important role in the performance of the devices. In this review, we introduce the evolution of electron and hole transporting materials in PSCs in recent years and summarize some typical charge transporting materials and their applications in PSCs. For electron transporting materials, metal oxides(TiO_(2), SnO_(2) and ZnO) and organic materials(fullerenes, non-fullerenes and their derivatives)are the most widely used materials in PSCs. For hole transporting materials, small molecule spiro-OMeTAD(2,2’,7,7’-Tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9’-spirobifluorene), polymer PEDOT:PSS(poly(3,4-ethylenedioxythiophene): polystyrene sulfonate), PTAA(poly-[bi(4-phenyl)](2,4,3-trimethylphenyla-mine)), P3 HT(poly(3-hexythiophene)) and inorganic materials(NiOx, CuSCN, CuO) are adopted in PSCs. Finally, different types of charge transporting materials are summarized and their future development is prospected.

Overexpression of GhFIM2 propels cotton fiber development by enhancing actin bundle formation

Cell elongation and secondary wall deposition are two consecutive stages during cotton fiber development. The mechanisms controlling the progression of these two developmental phases remain largely unknown. Here, we report the functional characterization of the actin-bundling protein GhFIM2 in cotton fiber. Overexpression of GhFIM2 increased the abundance of actin bundles, which was accompanied with accelerated fiber growth at the fastelongating stage. Meanwhile, overexpression of GhFIM2 could propel the onset of secondary cell wall biogenesis. These results indicate that the dynamic rearrangement of actin higher structures involving GhFIM2 plays an important role in the development of cotton fiber cells.

MdbHLH3 modulates apple soluble sugar content by activating phosphofructokinase gene expression

Sugars are involved in plant growth,fruit quality,and signaling perception.Therefore,understanding the mechanisms involved in soluble sugar accumulation is essential to understand fruit development.Here,we report that Md PFPβ,a pyrophosphatedependent phosphofructokinase gene,regulates soluble sugar accumulation by enhancing the photosynthetic performance and sugar-metabolizing enzyme activities in apple(Malus domestica Borkh.).Biochemical analysis revealed that a basic helix-loop-helix(b HLH)transcription factor,Mdb HLH3,binds to the Md PFPβpromoter and activates its expression,thus promoting soluble sugar accumulation in apple fruit.In addition,Md PFPβoverexpression in tomato influenced photosynthesis and carbon metabolism in the plant.Furthermore,we determined that Mdb HLH3 increases photosynthetic rates and soluble sugar accumulation in apple by activating Md PFPβexpression.Our results thus shed light on the mechanism of soluble sugar accumulation in apple leaves and fruit:Mdb HLH3 regulates soluble sugar accumulation by activating Md PFPβgene expression and coordinating carbohydrate allocation.