Mid-term survival of the Optimys short stem: A prospective case series of 500 patients

BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.

Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients

Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.

PCNA、Bcl-2及EGFR在喉癌组织中的表达及与临床病理特征、生存的关系

目的探讨增殖细胞核抗原(PCNA)、B淋巴细胞瘤-2(Bcl-2)及表皮生长因子受体(EGFR)在喉癌组织中的表达及与临床病理特征、生存的关系。方法选取2017年3月—2020年1月在苏州大学附属第一医院因喉癌行手术治疗的92例患者的喉癌组织及对应癌旁组织标本。检测癌组织与癌旁组织PCNA mRNA、Bcl-2mRNA、EGFR mRNA相对表达量,多元线性回归分析其癌组织表达与临床病理特征的关系。随访3年,采用Kaplain-Maier曲线分析不同PCNA、Bcl-2、EGFR表达水平患者生存情况差异。结果癌组织PCNA mRNA、Bcl-2 mRNA、EGFR mRNA相对表达量高于癌旁组织(P<0.05)。不同年龄、肿瘤部位患者PCNA mRNA、Bcl-2 mRNA、EGFR mRNA相对表达量比较,差异无统计学意义(P>0.05);低分化,临床分期Ⅲ、Ⅳ期及淋巴结转移患者PCNA mRNA、Bcl-2 mRNA、EGFR mRNA相对表达量分别高于中、高分化,临床分期Ⅰ、Ⅱ期,无淋巴结转移患者(P<0.05)。多元线性回归分析结果显示,肿瘤分化程度、临床分期、淋巴结转移是喉癌组织PCNA mRNA、Bcl-2 mRNA、EGFR mRNA表达的影响因素。Kaplain-Maier曲线分析结果显示,PCNA mRNA高表达患者3年无进展生存率、总生存率分别为59.57%和70.21%,低于低表达患者的80.00%和88.89%(P<0.05);Bcl-2 mRNA高表达患者3年无进展生存率、总生存率分别为60.78%和70.59%,低于低表达患者的80.49%和90.24%(P<0.05);EGFR mRNA高表达患者3年无进展生存率、总生存率分别为59.09%和70.45%,低于低表达患者的79.17%、87.50%(P<0.05)。结论喉癌组织PCNA、Bcl-2、EGFR呈高表达,且其高表达状态与肿瘤分期高、分化程度低、淋巴结转移有关,PCNA、Bcl-2、EGFR表达水平可在一定程度上反映患者预后。

乳腺癌组织lncRNA CASC2、miR-532-3p表达水平与患者术后5年内生存的相关性

目的探究乳腺癌(BC)组织长链非编码RNA癌易感性候选基因2(lncRNA CASC2)、微小RNA-532-3p(miR-532-3p)表达与患者术后5年内生存的相关性。方法选择2015年1月—2018年6月大同市第五人民医院普通外科收治BC患者127例,术中收集BC组织及癌旁正常组织,荧光定量PCR法检测BC组织和癌旁正常组织中lncRNA CASC2、miR-532-3p表达;对BC患者术后进行为期5年的随访,记录患者5年内生存和死亡情况。比较癌旁正常组织和BC组织lncRNA CASC2及miR-532-3p表达,BC组织中lncRNA CASC2和miR-532-3p表达在不同临床病理特征中的差异,生存组和死亡组临床病理特征和BC组织中lncRNA CASC2及miR-532-3p表达的差异。分析BC组织lncRNA CASC2、miR-532-3p表达的相关性;BC组织中lncRNA CASC2和miR-532-3p表达与术后5年内生存的关系;影响BC患者术后5年内生存的因素;lncRNA CASC2、miR-532-3p对BC患者术后5年内生存的预测价值。结果BC组织中lncRNA CASC2表达水平低于癌旁正常组织,miR-532-3p表达水平高于癌旁正常组织(t/P=38.239/<0.001,49.406/<0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例lncRNA CASC2低表达组高于高表达组,而miR-532-3p低表达组低于高表达组(lncRNA CASC2:χ^(2)/P=17.361/<0.001、17.052/<0.001、14.694/<0.001、13.173/<0.001;miR-532-3p:χ^(2)/P=10.733/0.001、9.813/0.002、10.134/0.001、7.444/0.006);127例BC患者术后随访5年,生存99例(生存组),死亡28例(死亡组),肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例及miR-532-3p表达水平死亡组高于生存组,而lncRNA CASC2表达水平死亡组低于生存组[χ^(2)(t)/P=5.211/0.022、27.149/<0.001、27.990/<0.001、4.590/0.032、19.155/<0.001、10.818/<0.001];BC组织中lncRNA CASC2与miR-532-3p表达呈负相关(r/P=-0.561/<0.001);lncRNA CASC2高表达组BC患者术后5年内总生存率为89.23%(58/65),高于lncRNA CASC2低表达组66.13%(41/62)(χ^(2)/P=9.854/0.002);miR-532-3p高表达组BC患者术后5年内总生存率为65.57%(40/61),低于miR-532-3p低表达组89.39%(59/66)(χ^(2)/P=10.466/0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、有淋巴结转移、lncRNA CASC2低表达、miR-532-3p高表达均是影响BC患者术后5年内生存的独立危险因素[HR(95%CI)=2.255(1.192~4.263)、2.143(1.252~3.666)、3.089(1.386~6.887)、2.219(1.223~4.026)、2.606(1.174~5.788)、2.855(1.592~5.120)];lncRNA CASC2、miR-532-3p及二者联合预测BC患者术后5年内生存的AUC分别为0.840、0.852、0.908,二者联合预测的AUC大于lncRNA CASC2、miR-532-3p各自单独预测的AUC(Z/P=2.246/0.025、2.033/0.042)。结论BC组织中lncRNA CASC2表达下调,miR-532-3p表达上调,且术后5年内死亡的BC患者较存活患者变化更显著,二者表达与临床病理特征相关,对预测BC患者术后5年内生存情况价值较高。

YTH结构域家族蛋白2和叉头蛋白转录因子3在肺腺癌中的表达关系研究

目的 分析YTH结构域家族蛋白2(YTHDF2)及叉头蛋白转录因子3(FOXO3)在肺腺癌病人中的表达及与预后的关系。方法 收集2020年1月至2021年5月在郑州大学第一附属医院行手术治疗的肺腺癌病人癌组织及对应的癌旁组织(距离癌组织5 cm以上)80对,收集病人临床病理资料;利用癌症基因组图谱(TCGA)数据库查询YTHDF2、FOXO3基因在肺腺癌中的表达水平;采用免疫组织化学法检测YTHDF2、FOXO3蛋白在肺腺癌组织中的表达情况;分析YTHDF2、FOXO3蛋白水平与肺腺癌病人临床病理资料的关系;分析肺腺癌中YTHDF2与FOXO3基因表达水平的相关性;对病人进行为期3年的随访,分析病人3年累积生存率。结果 YTHDF2、FOXO3蛋白在肺腺癌组织中的高表达率分别为34.00%、26.00%,明显低于癌旁正常组织中79.48%、61.54%(P<0.05)。YTHDF2蛋白表达情况与肺腺癌病人年龄、淋巴结转移和分化程度相关(P<0.05);与TNM分期、性别无关(P>0.05);FOXO3蛋白表达情况与肺腺癌病人性别和分化程度相关(P<0.05);肺腺癌组织中YTHDF2蛋白高表达组和低表达组病人3年累积生存率分别为53.30%、14.00%,经log-rank比较,差异有统计学意义(P<0.05);FOXO3蛋白高表达组和低表达组病人3年累积生存率分别为64.50%、12.20%,经Log-Rank比较,差异有统计学意义(P<0.05)。结论 YTHDF2、FOXO3在肺腺癌组织中均低表达,与病人肿瘤分化程度及3年累积生存率有关,有望成为评估肺腺癌病人预后的生物标志物。

5-hydroxymethyl-2-furfural prolongs survival and inhibits oxidative stress in a mouse model of forebrain ischemia

In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.

Impacts of CO_2-driven seawater acidification on survival,egg production rate and hatching success of four marine copepods

Ecological experiments were conducted to examine the effects of seawater containing elevated par- tial pressure of carbon dioxide （p CO2 800 × 10 -6 , 2 000 × 10 -6 , 5 000 × 10 -6 and 10 000 × 10 -6 ） on the survival and reproduction of female Acartia pacifica, Acartia spinicauda, Calanus sinicus and Centropages tenuiremis, which are the dominant copepods in the southern coastal waters of China. The results show that the effects of elevated p CO2 on the survival rates of copepods were species-specific. C. sinicus, which was a macro-copepod, had a higher survival rate （62.01%–71.96%） than the other three species （5.00%–26.67%） during the eight day exposure. The egg production rates of C. sinicus, A. spinicauda and C. tenuiremis were significantly inhibited by the increased p CO2 and the exposure time duration. There were significantly negative impacts on the egg hatching success of A. spinicauda and C. tenuiremis in the p CO2 2 000 × 10 -6 and 10 000 × 10 -6 groups, and, in addition, the exposure time had noticeably impacts on these rates too. This study indicates that the reproductive performances of copepods were sensitive to elevated p CO2 , and that the response of different copepod species to acidified seawater was different. Furthermore, the synergistic effects of seawater acidification and climate change or other pollutant stresses on organisms should be given more attention.

Activation of the ERK 1/2 and STAT3 signaling pathways is required for 661W cell survival following oxidant injury

AIM: To evaluate the influence of hydrogen peroxide (H2O2) on mouse photoreceptor-derived 661W cell survival and to determine the effect of PD98059, an inhibitor for MEK1 (the direct upstream activator of ERK1/2), and S3I201, a STAT3-specific inhibitor on 661W cell survival after H2O2 exposure. METHODS: The mouse photoreceptor-derived 661W cells were cultured. 661W cells were treated for 12 hours with different concentrations (0, 0.25, 0.50, 0.75, 1mmol/L) of H2O2 and cell viability was determined by 3- (4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) (MTT) assay. 661W cells were treated with different concentrations H2O2 (0, 5, 10, 50, 500, 1000 mu mol/L) for 15 minutes or 1mmol/L H2O2 for different time points (0,5,10,15,30 minutes), and p-Tyr705-STAT3, STAT3, Phospho-p44/42 MAPK (Thr202/Tyr204), ERK1/2 were surveyed by immunoblot analysis. After treatment with 50 mu mol/L PD98059, or S3I201 for 1 hour, the inhibition efficiency of cell signal pathways was analyzed by immunoblot analysis and the effects of inhibitors on cell viability were determined by MTT. RESULTS: After treating with different concentrations of H2O2 for 12 hours, the cell viability of 661W cells decreased in concentration-dependent manner (P<0.05). Moreover, H2O2 induced phosphorylation of ERK1/2 and STAT3 in 661W cells (P <0.05). After pretreatment with 50 mu mol/L PD98059 or S3I201 for 1 hour, H2O2-induced phosphorylation of ERK1/2 or STAT3 was suppressed separately (P<0.05). Using PD98059 or S3I201 to inhibit ERK1/2 or STAT3 signal pathway, the cell viability of 661W cells decreased significantly (P<0.05). CONCLUSION: We demonstrated that the exposure of 661W cells to H2O2 increased the activation of ERK1/2 and STAT3 signal pathways. Activation of these pathways is required for 661W cell survival following oxidant injury.

Up-regulation of tumor necrosis factor-a pathway survival genes and of the receptor TNFR2 in gastric cancer

BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene expression.AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its relationship.METHODS Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNF-α signaling pathway(TNF, TNFR1,TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases.RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP,and NFKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNF-α pathway,including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8.CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.

食管腺鳞癌组织p63和人表皮生长因子受体2蛋白表达与临床病理特征的关系及其对患者生存的影响

目的分析p63和人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)蛋白表达在食管腺鳞癌(esophageal adenosquamous carcinoma,EASC)患者中的临床意义和预后价值。方法回顾性分析来自郑州大学第一附属医院省部共建食管癌防治国家重点实验室已建立的80万例食管癌临床诊疗和随访信息数据库和样本库的2005年12月至2021年12月确诊的115例EASC患者的临床资料。采用亲和素-生物素-过氧化物酶复合物(avidin-biotin-peroxidase complex,ABC)技术检测p63和HER2蛋白的表达。采用χ^(2)检验分析p63和HER2蛋白表达与患者临床病理特征间的关系。应用KaplanMeier法分析蛋白表达与患者预后的关系。采用Cox回归分析评估患者预后的影响因素。结果EASC患者男女比例为3.1∶1。男性和女性EASC患者在各临床病理特征方面比较,差异均无统计学意义(均P>0.05)。p63阳性患者的肿瘤家族史和淋巴结转移率均低于p63阴性患者(均P<0.05)。HER2阳性患者男性占比和淋巴结转移率均高于HER2阴性患者(均P<0.05)。p63和HER2阳性患者总生存均优于阴性患者(均P<0.05)。多因素Cox回归分析显示,p63表达、性别、分化程度和TNM分期均是EASC患者预后的独立影响因素(均P<0.05)。结论p63和HER2蛋白表达与EASC患者的预后及淋巴结转移密切相关,有望成为EASC患者的预后标志物及潜在治疗靶点。

Long-term survival and prognostic implications of Chinese type 2 diabetic patients with coronary artery disease after coronary artery bypass grafting

This study was conducted to determine the sur-vival rates of type 2 diabetic patients after coro-nary artery bypass grafting (CABG) surgery, and the prognostic factors related to all-cause mor-tality during a 7-year follow-up. The medical re-cords of 816 type 2 diabetic patients who un-derwent primary, isolated CABG surgery during 1997-2003 were studied. The Kaplan-Meier me- thod and Cox regression were used to estimate survival and the independence of prognostic factors associated with all-cause mortality. One hundred and five out of 816 patients expired during the 7-year period. The overall survival rate was 83.5% (95%CI: 78.7-88.3%). Associated prog- nostic factors varied by gender. For males, but not for females, smoking (RR=3.44, 95%CI: 1.01- 11.70), myocardial infarction (RR=4.77, 95% CI: 1.23-18.86), respiratory failure (RR=4.21, 95% CI: 1.48-7.99), cardiogenic shock (RR=12.58, 95% CI: 3.25-20.77), and congestive heart failure (RR= 3.77, 95%CI: 1.10-13.45) were significantly related to all-cause mortality. Older age at sur-gery (RR= 1.15, 95%CI: 1.04-1.27), emergent op-eration (RR= 21.29, 95%CI: 10.03-39.43), pul-monary ede-ma (RR=7.72, 95%CI: 1.89-15.59), and days of ICU stay (RR=1.05, 95%CI: 1.02-1.09) were significant- ly related to all-cause mortality in females only. In conclusion, several gen-der-related differences were noted pertaining to all-cause mortality and its relationship to smok- ing, myocardial infarction, respiratory failure, cardiogenic shock, congestive heart failure, older age at surgery, emergent operation, pul-monary edema, and days of ICU stay.

BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival

Objective： Bone morphogenetic protein receptor 2（BMPR2） and hypoxia-inducible factor 1-α（HIF1-α） existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown.Methods：To investigate the clinical significance of BMPR2 and HIF1-αin osteosarcoma,we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry.Meanwhile,we conducted a follow-up to examine the metastatic behavior and overall survival（OS）of osteosarcoma patients.Results：Among 103 tissues,61 cases had BMPR2-positive expression and 57 cases had HIF1-αpositive expression.A significant correlation was noticed between BMPR2 and HIF1-αexpression in osteosarcoma specimens（P=0.035）.Receiver-operating characteristic（ROC）curves were calculated to investigate the predictive value of the two markers in tumor metastasis.By means of univariate and multivariate analysis,BMPR2 and HIF1-αexpression,as well as higher tumor grade,were identified as significant risk factors for OS in patients with osteosarcoma.Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-αpositive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining.Conclusions：It can be concluded that BMPR2 and HIF1-αexpression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.

c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2

T 房间从祖先 thymocytes 被导出，哪个仅仅一个少数收到适当 TCR 信号，经历积极选择并且成熟。由于 thymocytes 的短 lifespan，为积极选择的前提是幸存。TCR 导致信号的 Bcl-2 表示被相信在断然选择 thymocytes 的幸存起一个主导的作用，但是 Bcl-2 怎么直接被调整，是未知的。这里，我们报导立即的早基因(IEG ) c-Fos 能刺激 Bcl-2 的表示，取决于在 Bcl-2 倡导者的一个特定的 AP-1-binding 地点。在 c-Fos 转基因(Fos-Tg ) 老鼠， c-Fos 绑在这个地点并且支持 Bcl-2 的表示。作为结果，展出的 Fos-Tg thymocytes 提高了幸存，和更多成熟单人赛积极(SP ) thymocytes 被产生，甚至在一个唯一的 TCR 背景上。TCR 全部剧目在 Fos-Tg 老鼠仍然保持正常。我们的结果作为在 Bcl-2 表示上发信号的 TCR 的 stimulatory 效果的调停人识别了 c-Fos。因此，作为 IEG，因为它的早反应能力， c-Fos 能快速救短命 thymocytes 的幸存在积极选择期间。我们的结果提供新奇卓见进调整断然选择 thymocytes 的幸存的机制。

曲妥珠单抗生物仿制药对比原研药治疗复发或转移性HER-2阳性乳腺癌的药物经济学评价

目的从卫生体系角度评估曲妥珠单抗生物仿制药(汉曲优)与原研药(赫赛汀)治疗复发或转移性人表皮生长因子受体2(HER-2)阳性乳腺癌的经济性。方法根据NCT03084237试验数据构建分区生存模型,模拟周期为3周,模拟时限为10年。以成本和质量调整生命年(QALY)为产出指标,采用成本-效用分析法评价上述2种方案的经济性。采用单因素敏感性分析和概率敏感性分析检验模型的稳健性。结果曲妥珠单抗生物仿制药组与原研药组的成本分别为111516.72、111122.30元,效用分别为1.52、1.36 QALYs,增量成本-效果比(ICER)为2465.12元/QALY,小于以3倍中国2023年人均国内生产总值(GDP)作为的意愿支付(WTP)阈值(268200元/QALY)。单因素敏感性分析结果表明,曲妥珠单抗生物仿制药费用与曲妥珠单抗原研药费用对ICER有较大影响。概率敏感性分析结果显示,当WTP阈值大于14902元/QALY时,曲妥珠单抗生物仿制药组具有经济性的概率为100%。结论当WTP阈值为3倍中国2023年人均GDP(268200元/QALY)时,与曲妥珠单抗原研药相比,曲妥珠单抗生物仿制药治疗复发或转移性HER-2阳性乳腺癌具有较好的经济性。

拉帕替尼联合微波热疗治疗HER2阳性晚期乳腺癌的疗效

目的 研究拉帕替尼联合微波热疗治疗人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阳性晚期乳腺癌患者的疗效。方法 选取2019年1月至2020年1月于湖州市中心医院就诊的HER2阳性晚期乳腺癌患者134例,根据抽签法将其分为对照组和观察组,每组各67例。两组均使用拉帕替尼治疗,观察组患者在此基础上联合微波热疗治疗。比较两组患者治疗前后的肿瘤标志物[糖类抗原153(carbohydrate antigen 153,CA153)、癌胚抗原(carcinoembryonic antigen,CEA)、组织多肽抗原(tissue peptide antigen,TPA)]、循环肿瘤细胞(circulating tumor cell,CTC)数量、波形蛋白表达和生存质量,统计两组患者的临床疗效及生存状态。结果 治疗后,两组患者的CA153、CEA、TPA、CTC数量、波形蛋白表达均显著低于本组治疗前,生存质量评分均显著高于本组治疗前(P<0.05);观察组患者的CA153、CEA、TPA、CTC数量、波形蛋白表达均显著低于对照组,生存质量评分显著高于对照组(P<0.05)。观察组患者的治疗总有效率显著高于对照组(χ^(2)=5.350,P=0.021)。两组患者的不良反应比较差异均无统计学意义(P>0.05)。随访24个月,观察组患者的总生存期、无进展生存期均显著长于对照组,24个月累积生存率显著高于对照组(P<0.05)。结论 拉帕替尼联合微波热疗治疗HER2阳性晚期乳腺癌效果良好,可改变波形蛋白表达抑制疾病进展,延长患者的生存期。

高CO_(2)浓度对草地贪夜蛾和斜纹夜蛾幼虫在小麦和人工饲料上种间竞争的影响

大气中CO_(2)浓度增加直接或间接影响昆虫的发生和为害,可能会影响入侵害虫的危害性及其与本地近缘种的互作关系。然而,CO_(2)浓度升高对入侵害虫草地贪夜蛾Spodoptera frugiperda及其本地近缘种斜纹夜蛾Spodopteralitura种间竞争的影响尚不清楚。本研究模拟环境条件,设置了CO_(2)正常浓度(400μL/L)和倍增浓度(800μL/L),将草地贪夜蛾幼虫与斜纹夜蛾幼虫以25/5、20/10、15/15、10/20和5/25的比例混合,分别在寄主植物小麦和人工饲料上饲养,比较研究了CO_(2)浓度升高对其种间竞争关系的影响。结果表明:(1)在所有试验处理中,斜纹夜蛾幼虫的死亡率均会达100%,而且在高CO_(2)浓度环境下斜纹夜蛾幼虫全部死亡所需时间更短。而高CO_(2)浓度下,又以小麦为食的25/5和20/10混合比例中用时最短,仅需4.00 d;(2)各混合比例中,草地贪夜蛾幼虫的平均存活天数均显著高于斜纹夜蛾幼虫,其中在高CO_(2)浓度下以小麦为食时,各混合比例中草地贪夜蛾幼虫较斜纹夜蛾幼虫平均存活天数的差距最大,分别为5.99 d、6.96 d、6.22 d、6.15 d和5.21 d。而且高CO_(2)浓度下草地贪夜蛾幼虫与斜纹夜蛾幼虫的平均存活天数相对值均高于正常CO_(2)浓度对照组,其中在以小麦为食时,高CO_(2)浓度组的平均存活天数相对值分别达到正常CO_(2)浓度的1.08倍、1.22倍、1.26倍、1.31倍和1.13倍;(3)两种CO_(2)浓度下草地贪夜蛾幼虫的平均相对生长率均高于斜纹夜蛾幼虫,而且高CO_(2)浓度下草地贪夜蛾幼虫与斜纹夜蛾幼虫的平均相对生长率相对值高于对照,其中在以饲料为食时,在比例25/5、20/10、15/15中,分别达到正常CO_(2)浓度的168.03倍、3.38倍和2.91倍。由此说明,在两种CO_(2)浓度下,草地贪夜蛾幼虫与斜纹夜蛾幼虫在小麦和人工饲料上的种间竞争中,草地贪夜蛾幼虫均具有较强的竞争优势,尤其在高CO_(2)浓度下,更有利于其竞争力的发挥。研究结果为揭示未来CO_(2)浓度升高对入侵害虫草地贪夜蛾种群适应性的影响及其科学防控提供了基础数据。

非小细胞肺癌晚期患者白细胞介素-2、白细胞介素-6、肿瘤坏死因子-α和γ干扰素对生存情况的预测价值

目的分析非小细胞肺癌(NSCLC)晚期患者血清中白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和γ干扰素(IFN-γ)变化与生存率的相关性。方法回顾性分析2021年10月至2022年9月在抚州市第一人民医院肿瘤内科确诊的60例NSCLC晚期患者临床资料,作为观察组,根据患者入院6个月后的预后情况将患者分为生存组(n=41)和死亡组(n=19),同期选择入院体检的66例健康人群为健康组。记录患者入院24 h内和治疗2个周期后的IL-2、IL-6、TNF-α、IFN-γ水平,比较治疗2个周期后的生存组和死亡组患者的IL-2、IL-6、TNF-α、IFN-γ水平,以患者的预后情况作为最终变量绘制NSCLC患者预后的ROC曲线图。结果健康组的IL-6水平低于观察组,IL-2、TNF-α和IFN-γ水平均高于观察组,差异均有统计学意义(P<0.05)。患者入院24 h内,死亡组IL-6水平高于生存组,差异有统计学意义(P<0.05)。两组患者入院治疗2个周期后,患者的IL-2水平较入院24 h内低,IL-6、TNF-α和IFN-γ水平较24 h内的指标水平高,差异均有统计学意义(P<0.05)。治疗2个周期后,生存组的IL-6较死亡组低,差异有统计学意义(P<0.05)。ROC结果显示,IL-6水平鉴别诊断NSCLC患者的预后的ROC曲线下面积为0.738,敏感度为89.47%,特异性为65.85%,此时IL-6水平的截断值为60.731 pg/ml(P<0.05)。结论NSCLC晚期患者的IL-6水平对其预后具有一定的预测效能,可以为临床NSCLC患者的治疗方案提供指导作用。

Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery

BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this disease.LATS2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric cancer.AIM To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM staging.METHODS A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted.The patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic model.The performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision curves.RESULTS The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set.Area under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination ability.Calibration plots confirmed the high concordance between the predictions and actual survival outcomes.CONCLUSION We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery.This model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical outcomes.Further validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.

血清CEA、CA19-9、β_(2)-MG表达与膀胱癌患者吡柔比星膀胱灌注化疗疗效和生存期相关分析

目的探讨膀胱癌患者血清癌胚抗原(CEA)、癌抗原199(CA19-9)、β_(2)微球蛋白(β_(2)-MG)水平与膀胱癌患者吡柔比星膀胱灌注化疗疗效和生存期的关系。方法选取2021年3月~2023年4月在南阳市第一人民医院接受吡柔比星膀胱灌注化疗的98例膀胱癌患者作为研究对象,根据化疗结果分为化疗有效组(52例)和化疗无效组(46例)。比较两组患者的临床资料和血清CEA、CA19-9、β_(2)-MG水平,并进行单因素和多因素分析、生存分析及Cox回归分析。结果化疗有效组血清CEA、CA19-9、β_(2)-MG水平均低于化疗无效组(P<0.001)。进一步经多因素Logistic回归分析显示血清CEA水平是影响化疗效果和生存期的独立危险因素,高表达者化疗效果差,预后不良。血清CA19-9、β_(2)-MG水平也与化疗效果相关,但不是独立影响因素。结论血清CEA水平是预测膀胱灌注化疗疗效和生存期的重要指标,建议对膀胱癌患者进行血清CEA、CA19-9、β_(2)-MG检测,以指导个体化治疗方案的制定。