Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway

BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.

Yield Increasing and Quality Improving Effects of Smash-ridging Method("4453" Effects) and Its Potential in Benefiting the Nation and the People

Yuan Longping proposed that smash-ridging technology could be extend-ed widely nationwide. ln the research, smash-ridging technology reconstruct cultiva-tion layers with loose soils in agricultural fields, creating ＂4453＂ effects, as fol ows： ＂Four increases＂ include to increase loosen soil quantity in cultivation layers, soil nutri-ents use, ＂water pool＂ in soils, and ＂oxygen pool＂ in soils. Four reductions are to reduce soil erosion, carbon emission, salt content and heavy metal in soils. Five resistances refer to improve crop resistance capacity in terms of drought, high tem-perature, lower temperature, disease and lodging. Three improvements indicate to enhance photosynthetic efficiency over 10%, yield in 10%-30% and quality over 5%. lt is researched that without additional chemical fertilizer, yield could increase by 10% by labor force, animal, tractor or smash-ridging machine. What’s more, by smash-ridging cultivation, the depth can be 20 times or higher compared with tractor cultivation, with looser soils. lt is estimated that if smash-ridging cultivation is applied once in agricultural lands in China, present soil layers can be twice as deep as present. Specifical y, the thickness of loose soil-layers could be extended from 10-18 cm at present to 25-35 cm, and natural rainfal would increase by 40 bil ion cm3. After vitalization of soil nutrients, chemical fertilizer would decrease by 7 bil ion kg, and the increased c rops would feed more than 300 mil ion population as per yield at 7 50 kg/hm2.

PD-1抗体联合胸腺肽α1、肝动脉灌注化疗治疗原发性肝癌合并门静脉癌栓的疗效观察

目的探究程序性死亡蛋白-1(PD-1)抗体联合胸腺肽α1、肝动脉灌注化疗(HAIC)治疗原发性肝癌合并门静脉癌栓(PVTT)的疗效。方法选择2021年8月—2022年8月石家庄市第五医院介入医学科治疗的原发性肝癌合并PVTT患者50例,以随机数字表法分为PD-1组(n=25)和对照组(n=25)。对照组给予胸腺肽α1与HAIC治疗,PD-1组给予PD-1抗体联合胸腺肽α1、HAIC治疗。比较2组患者客观缓解率、肝功能指标、血清肿瘤标志物、免疫功能指标。结果PD-1组的客观缓解率高于对照组(48.00%vs.20.00%,χ^(2)/P=4.367/0.037)。治疗6周、12周后,2组Alb均升高,TBil、ALT均降低,且治疗12周后PD-1组升高/降低幅度显著大于对照组(t/P=2.897/0.006、3.424/<0.001、2.658/<0.001);2组患者甲胎蛋白(AFP)、胰岛素样生长因子结合蛋白-2(IGFBP-2)均降低,且治疗12周后PD-1组低于对照组(t/P=3.934/<0.001、5.992/<0.001);2组患者CD8^(+)均降低,CD4^(+)/CD8^(+)均升高,且治疗12周后PD-1组降低/升高幅度大于对照组(t/P=3.110/<0.001、2.414/0.020)。结论PD-1抗体联合胸腺肽α1、HAIC治疗能够改善原发性肝癌合并PVTT患者的肝功能和免疫功能,降低血清肿瘤标志物水平,延缓肿瘤进展,疗效显著。

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients

AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.

Flow behavior in microchannel made of different materials with wall slip velocity and electro-viscous effects

In a microfluidic system, flow slip velocity on a solid wall can be the same order of magnitude as the average velocity in a microchannel. The flow-electricity interaction in a complex microfluidic system subjected to joint action of wall slip and electro-viscous effect is an important topic. This paper presents an analytic solution of pressuredriven liquid flow velocity and flow-induced electric field in a two-dimensional microchannel made of different materials with wall slip and electro-viscous effects. The Poisson- Boltzmann equation and the Navier-Stokes equation are solved for the analytic solutions. The analytic solutions agree well with the numerical solutions. It was found that the wall slip amplifies the fow-induced electric field and enhances the electro-viscous effect on flow. Thus the electro-viscous effect can be significant in a relatively wide microchannel with relatively large kh, the ratio of channel width to thickness of electric double layer, in comparison with the channel without wall slip.

Potential Toxicological and Cardiopulmonary Effects of PM2,5 Exposure and Related Mortality:Findings of Recent Studies Published during 2003-2013

Air pollution has environmental issue owing become a serious to its diverse harmful effects on the physical and biological environment. According to the Environmental Protection Agency （EPA） and the World Health Organization （WHO）, air pollution affects millions of people worldwide. Hundreds of thousands of deaths each year and a range of diseases, particularly among vulnerable groups （i.e., children, the elderly, and people with special medical conditions）, are attributed to air pollution. These effects are not always caused by single pollutant in the air; rather, they are considered consequences of the multi-pollutants to which people are simultaneously exposed.

Tumor-feeding artery diameter reduction is associated with improved short-term effect of hepatic arterial infusion chemotherapy plus lenvatinib treatment

BACKGROUND Recently,hepatic arterial infusion chemotherapy(HAIC)plus lenvatinib has been frequently used to treat unresectable hepatocellular carcinoma(uHCC)in China.In the clinic,the hepatic arteries of some patients shrink significantly during this treatment,leading to improved short-term efficacy.AIM To investigate the relationship between the shrinkage of hepatic arteries and the short-term effect of HAIC plus lenvatinib treatment.METHODS Sixty-seven participants with uHCC were enrolled in this retrospective study.The patients received HAIC every 3 wk,followed by oral lenvatinib after the first HAIC course.Hepatic artery diameters were measured on CT before treatment and after 1 and 2 mo of treatment.Meanwhile,the changes in tumor capillaries were also examined on pathological specimens before and after 1 mo of treatment.The antitumor response after 1,3,and 6 mo of treatment was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST).The relationship between the changes in vessel diameters and the short-term effect of the combination treatment was evaluated by receiver-operating characteristic and logistic regression analyses.RESULTS The hepatic artery diameters were all significantly decreased after 1 and 2 mo of treatment(P<0.001),but there was no difference in the vessel diameters between 1 and 2 mo(P>0.05).The microvessel density in the tumor lesions decreased significantly after 1 mo of combination treatment(P<0.001).According to mRECIST,46,41,and 24 patients had complete or partial responses after 1,3,and 6 mo of treatment,respectively,whereas 21,21,and 32 patients had a stable or progressive disease at these times,respectively.Shrinkage of the tumor-feeding artery was significantly associated with the tumor response after 1,3,and 6 mo of treatment(P<0.001,P=0.004,and P=0.023,respectively);however,changes in other hepatic arteries were not significantly associated with the tumor response.Furthermore,shrinkage of the tumor-feeding artery was an independent factor for treatment efficacy(P=0.001,P=0.001,and P=0.002 and 1,3,and 6 mo,respectively).CONCLUSION The hepatic arteries shrank rapidly after treatment with HAIC plus lenvatinib,and shrinkage of the tumor-feeding artery diameter was closely related to improved short-term efficacy.

Cost-effectiveness analysis of colon cancer treatments from MOSIAC and No.16968 trials

AIM: To compare XELOX and FOLFOX4 as colon cancer adjuvant chemotherapy based on MOSAIC and No. 16968 trails from Chinese cost-effectiveness perspective. METHODS: A decision-analytic Markov model was developed to compare the FOLFOX4 and XELOX regimens based MOSAIC and No. 16968 trial. Five states were included in our Markov model: well (state 1), minor toxicity (state 2), major toxicity (state 3), quitting adjuvant chemotherapy (state 4), and death due to adjuvant chemotherapy (state 5). Transitions among the 5 states were assumed to be Markovian. Costs were calculated from the perspective of the Chinese health-care payer. The utility data were taken from published studies. Sensitivity analyses were used to explore the impact of uncertainty factors in this cost-effectiveness analysis. RESULTS: Total direct costs of FOLFOX4 and XELOX per patient were $ 19884.96 +/- 4280.30 and $ 18113.25 +/- 3122.20, respectively. The total fees related to adverse events per patient during the entire treatment were $ 204.75 +/- 16.80 for the XELOX group, and $ 873.72 +/- 27.60 for the FOLFOX4 group, and the costs for travel and absenteeism per patient were $ 18495.00 for the XELOX group and $ 21,352.68 for the FOLFOX4 group. The base-case analysis showed that FOLFOX4 was estimated to produce an additional 0.06 in quality adjusted life years (QALYs) at an additional cost of $ 3950.47 when compared to the XELOX regimen over the model time horizon. The cost per QALY gained was $ 8047.30 in the XELOX group, which was $ 900.98 less than in the FOLFOX4 group ($ 8948.28). The one way sensitivity analysis demonstrated that the utility for the well state and minor toxicity state greatly influenced the incremental cost-effectiveness ratio of FOLFOX4. CONCLUSION: In term of cost-comparison, XELOX is expected to dominate FOLFOX4 regimes; Therefore, XELOX provides a more cost-effective adjuvant chemotherapy for colon cancer patients in China. c 2014 Baishideng Publishing Group Inc. All rights reserved.

Effects of natural-cerebrolysin-containing serum on neurotoxicity and synaptogenesis in amyloid-beta 1-40-induced Alzheimer's disease in vitro models

BACKGROUND： Neuronal loss, synapse mutilation, and increasing malnourished axons are pathologically related to Alzheimer＇s disease. Microtubule-associated protein 2 （MAP2） is of importance for neuronal, axonal, and dendritic generation, extension, and stabilization, as well as for the regulation of synaptic plasticity. OBJECTIVE： To investigate the antagonistic effects of natural-cerebrolysin-containing serum on beta amyloid protein 1-40 （Aβ1-40）-induced neurotoxicity from the standpoints of cell proliferation, synaptogenesis, and cytoskeleton formation （MAP2 expression）. DESIGN, TIME AND SETTING： A paralleled, controlled, neural cell, and molecular biology experiment was performed at the Institute of Integrated Chinese and Western Medicine, Shenzhen Hospital, Southern Medical University between February 2006 and April 2008. MATERIALS： PC12 cells, derived from the rat central nervous system, were purchased from Shanghai Institute of Cell Biology, Chinese Academy of Sciences, China. A β1-40 was provided by Sigma, USA. Natural-cerebrolysin was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. The natural-cerebrolysin was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae）, and Yixingye （Ginkgo Leaf） in a proportion of 1：2：2. Following conventional water extraction technology, an extract （1：20） was prepared. Each gram of extract equaled 20 grams of crude drug. In a total of 12 adult male New Zealand rabbits, six underwent intragastric administration of natural-cerebrolysin extract for 1 month to prepare natural-cerebrolysin-containing serum, and the remaining six rabbits received intragastric administration of physiological saline to prepare normal blank serum. METHODS： An AIzheimer＇s disease in vitro model was induced in PC12 cells using Aβ1-40. The cells were incubated with varying doses of natural-cerebrolysin-containing serum （2.5%, 5%, and 10%）. Normal blank serum-treated PC12 cells served as a blank control group. MAIN OUTCOME MEASURES： Through the use of inverted phase contrast microscope, cell morphology and neurite growth were observed, neurite length was measured, and the percentage of neurite-positive cells was calculated. Cell proliferation rate was determined by MTT assay, and MAP 2 expression was detected by fluorescent immunocytochemistry. RESULTS： Following Aβ1-40 treatments, some PC12 cells were apoptotic/dying, and only a few short neurites were observed. Following interventions with natural-cerebrolysin-containing serum, the PC12 cells proliferated, there was an increased number of neurites, and neurite length was enhanced. After middle- and high-dose natural-cerebrolysin treatments, the percentage of neurite-positive cells, as well as the average length of neurites, was significantly greater than the normal blank serum-treated PC12 cells （P 〈 0.05 or P 〈 0.01）. Compared with the blank control group, MAP2 expression in the Aβ1-40-treated PC12 cells was significantly inhibited, and the cell proliferation rate was significantly decreased （P 〈 0.01）. Following incubations with natural-cerebrolysin-containing serum, MAP2 expression and cell proliferation rate in the PC12 cells were significantly increased in a dose-dependent manner, compared with treatments with blank control serum （P 〈 0.05 or P 〈 0.01 ）. CONCLUSION： Natural-cerebrolysin exhibited antagonistic effects on neurotoxicity in Aβ1-40 induced Alzheimer＇s disease in vitro models. These effects were likely related to cell proliferation and the upregulation of intracellular MAP2 expression.

Effects of natural cerebrolysin on protective proteins and pro-apoptotic molecules in mesenchymal stem cells following beta-amyloid peptide1-40-induced endoplasmic reticulum stress

BACKGROUND： Studies have demonstrated that β-amyloid peptide （Aβ）, a characteristic pathological product of Alzheimer＇s disease （AD）, results in neuronal endoplasmic reticulum stress （ERS）. However, the mechanisms of traditional Chinese medicine against ERS in AD are poorly understood. OBJECTIVE： To measure expression levels of protective proteins （GRP78 and GRP94） of ER molecular partners and pro-apoptotic Caspase-12 ER membrane expression following application of traditional Chinese medicine natural cerebrolysin （NC） to treat Aβ1-40-induced ERS. DESIGN, TIME AND SETTING： A parallel-controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital of Southern Medical University between September 2006 and November 2008. MATERIALS： Sprague Dawley male rats, 6-8 weeks old, were used to harvest tibial and femoral bone marrow. Isolation and purification of mesenchymal stem cells （MSCs） were established from the whole bone marrow by removing non-adherent cells in primary and passage cultures. Aβ1-40 was provided by Sigma, USA. NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. NC was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae）, and Yinxingye （Ginkgo Leaf） in a proportion of 1 ： 2： 2. Following conventional water extraction technology, an extract （1 ： 20） was prepared. Six adult, male, New Zealand rabbits underwent intragastric administration of NC extract （0.976 g/kg per day） for 1 month to prepare NC-positive serum, and the remaining 6 rabbits received intragastric administration of physiological saline to prepare normal blank serum. METHODS： A total of 500 nmol/L Aβ1-40 was used to establish ERS models of primary cultured MSCs. AD cell models were incubated with different doses of NC-positive serum （2.5%, 5%, and 10%）. MSCs treated with normal blank serum served as normal blank controls. MAIN OUTCOME MEASURES： Reverse transcription-polymerase chain reaction and fluorescent immunocytochemistry were respectively used to measure mRNA and protein expression levels of GRP78, GRP94, and Caspase-12 in MSCs. RESULTS： Following Aβ1-40 exposure, mRNA and protein expression levels of GRP78 and GRP94, as well as Caspase-12, significantly increased （P 〈 0.05）, suggesting successful establishment of ERS models. Following NC-positive serum application, mRNA and protein expression levels of GRP78 and GRP94 in MSCs significantly increased （P 〈 0.05 or P 〈 0.01）. However, mRNA and protein expression levels of Caspase-12 significantly decreased （P 〈 0.05, or P 〈 0.01） compared with the ERS model group. These effects were dose-dependent. CONCLUSION： NC downregulated Caspase-12 expression and upregulated GRP78 and GRP94 expression in MSCs in a dose-dependent manner under the state of Aβ1-40-induced ERS.

Synergistic Effect in Mixed Capillary Gas Chromatographic Stationap Phases Containing Heptakis(2,3,6-tri-o-pentyl)-β-cyclodextrin and Dibenzo-18-crown-6

used－silical capillary columns containing heptakis（2、3、6－tri－o－pentyl）-β-cyclodextrinand dibenzo-18-crown-6 were prepared．By studying the selectivity of mixed stationary phases forsome solute pairs.as well as comparing with the heptakis（2．3、6-tri-O-pentyl）-β-cyclodextrin and thedibenzo-18-crown-6 used as individual stationary phase、the synergistic effects were observed.These effects were affected by the column temperature．mixed ratio and linear velocity of carrier gas．

Natural convection flow of a couple stress fluid between two vertical parallel plates with Hall and ion-slip effects

The Hall and ion-slip effects on fully developed electrically conducting couple stress fluid flow between vertical parallel plates in the presence of a temperature dependent heat source are investigated. The governing non-linear partial differential equations are transformed into a system of ordinary differential equations using similarity transformations. The resulting equations are then solved using the homotopy analysis method （HAM）. The effects of the magnetic parameter, Hall parameter, ion-slip parameter and couple stress fluid parameter on velocity and temperature are discussed and shown graphically

替雷利珠单抗联合化疗一线治疗局部晚期不可切除或转移性胃或胃食管结合部腺癌的成本-效果分析

目的评价替雷利珠单抗联合化疗一线治疗局部晚期不可切除或转移性胃或胃食管结合部腺癌的经济性。方法从我国卫生体系角度出发,利用RATIONALE-305试验和相关文献数据建立分区生存模型,循环周期为3周,模拟时限为10年,贴现率为5%。以质量调整生命年(QALYs)为健康产出指标,评价替雷利珠单抗联合化疗对比安慰剂联合化疗一线治疗局部晚期不可切除或转移性胃或胃食管结合部腺癌的经济性,并进行单因素敏感性分析和概率敏感性分析。结果基础分析结果显示,与安慰剂联合化疗相比,替雷利珠单抗联合化疗方案可使患者多获得0.268QALYs,但治疗成本会增加70404.81元,增量成本-效果比(ICER)为262431.62元/QALY,低于3倍2023年我国人均国内生产总值(GDP)的意愿支付阈值(268074元/QALY)。单因素敏感性分析结果显示,无进展生存效用值和替雷利珠单抗药品成本对ICER值的影响较大。概率敏感性分析结果显示,当WTP阈值为3倍2023年我国人均GDP时,替雷利珠单抗具有经济性的概率为53.3%。结论当WTP阈值为3倍2023年我国人均GDP时,与安慰剂联合化疗方案相比,替雷利珠单抗联合化疗一线治疗局部晚期不可切除或转移性胃或胃食管结合部腺癌具有经济性。

Cost-Effectiveness Analysis of Neoadjuvant Chemotherapy with Zoledronic Acid for HER2-Negative Breast Cancer in Japan: The JONIE1 Study

Objective: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption. Adding ZOL to neoadjuvant chemotherapy has been shown to have potential anticancer benefits in women with HER2-negative breast cancer. The objective of the present study was to investigate ZOL’s cost-effectiveness from the perspective of health care payers in Japan. Methods: A Markov model was developed to evaluate the costs and effectiveness associated with ZOL + chemotherapy (CTZ) and chemotherapy (CT) alone over a 10-year time horizon. Monthly transition probabilities were estimated according to JONIE1 (Japan Organization of Neoadjuvant Innovative Expert) Study data and an extrapolated Weibull model. Health outcomes were measured in quality-adjusted life years (QALYs). Costs were calculated using year-2018 Japanese yen (JPY) (1.00 US dollars (USD) = 110.4 JPY). Model robustness was addressed through one-way and probabilistic sensitivity analysis. The costs and QALYs were discounted at a rate of 2% per year. Results: In the base case, the use of CTZ was associated with a gain of 3.94 QALYs. The incremental cost per QALY of the CTZ gain was 681,056.1 JPY (6168.99 USD) per QALY. Conclusion: It is convincing that neoadjuvant CTZ for patients with breast cancer would be expected to have statistically significant clinical efficacy. Addition of ZOL to CT might be a cost-effective option compared with CT alone.

Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic proliferation of vascular smooth muscle cells

Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.

The effect of Supplementing Qi and Nourishing Yin combined with chemotherapy for lung cancer： a meta-analysis

Objective： To evaluate whether herbs of supplementing Qi and nourishing Yin combined with chemotherapy （versus chemotherapy alone） improve survival, increase tumor response, improve performance status or reduce chemotherapy toxicity in patients with lung cancer. Methods： Searching the randomized controlled trials （RCT） studies from the databases （China HowNet database, Wan Fang database, VIP database, Master Thesis and Pubmed） between January 2013 and January 2017. RevMan 5.3 software was used to evaluate the quality of these collected papers. Results： Of 48 potentially relevant publications, 10 randomized studies representing 691 patients met inclusion criteria with 369 cases in the supplementing Qi and nourishing Yin plus Chemotherapy group （Herbs ＋ Chem group） and 322 cases in Chemotherapy group （Chem only group）. There were significant differences between Herbs ＋ Chem group and Chem only group in improving the treatment efficacy and reducing the side effects of chemotherapy （P 〈 0.001 for all）. There were also significant differences between the two groups in tumor response and quality of life （P 〈 0.001 for all）. Conclusion： Herbs of supplementing Qi and nourishing Yin may increase chemotherapy effectiveness, reduce chemotherapy toxicity and improve the quality of life of patients with lung cancer when combined with chemotherapy.

Effect of Astragalus Injection Combined with Chemotherapy on Qual ity of Life in Patients with Advanced Non-small Cell Lung Cancer

Objective: To observe the effect of Astragalus injection (AI) combined with chemotherapy on quality of life (QOF) in patients with advanced non-small cell lung caner (NSCLC). Methods: Sixty NSCLC patients were randomly divided into the treated group (n=30,treated with AI combined with chemotherapy) and the control group (n=30, treated with chemotherapy alone). Chemotherapy of MVP protocol was applied to both groups. AI was supplemented to the treated group by intravenous dripping 60 ml per day. Treatment of 21-28 days consisted one treatment cycle, and 2-3 cycles were applied. WResults: The effective rate in the treated group was 40.0% and in the control group was 36.7%, the mean remission rate in them being 5.4 month s and 3.3 months, the median survival period 11 month and 7 month and the 1-year survival rate 46.75% and 30.0%, respectively, the difference of these indexes between the two groups were all significant (P<0 05). Moreover, the clinical improving rate and QOF elevation rate in the treated group was 80.4% and 43.3%, as compared with those in the control group (50.0% and 23.3% respectively), the different was also significant (P<0 01). Conclusion: AI combined with chemotherapy can significantly improve the QOF in NSCLC patients of advanced stage.

Is CA19-9 effective in predicting chemotherapeutic response in patients with synchronous liver metastases with colorectal cancer?

Evaluation of response to chemotherapy in colorectal cancer patients with synchronous liver metastases is important in terms of treatment management.In this Letter to the Editor,several issues in the article are discussed.For the comparison of carbohydrate antigen 19-9(CA19-9)values referenced in the study,the patient group was not matched for cancer stage.Therefore,it may be more appropriate to select and compare CA19-9 values in patients with same-stage cancer.

Influence of Rashba spin–orbit coupling on Josephson effect in triplet superconductor/two-dimensional semiconductor/triplet superconductor junctions

We study theoretically Josephson effect in a planar ballistic junction between two triplet superconductors with pwave orbital symmetries and separated by a two-dimensional(2D)semiconductor channel with strong Rashba spin–orbit coupling.In triplet superconductors,three types of orbital symmetries are considered.We use Bogoliubov–de Gennes formalism to describe quasiparticle propagations through the junction and the supercurrents are calculated in terms of Andreev reflection coefficients.The features of the variation of the supercurrents with the change of the strength of Rashba spin–orbit coupling are investigated in some detail.It is found that for the three types of orbital symmetries considered,both the magnitudes of supercurrent and the current-phase relations can be manipulated effectively by tuning the strength of Rashba spin–orbit coupling.The interplay of Rashba spin–orbit coupling and Zeeman magnetic field on supercurrent is also investigated in some detail.