论著

血清乳酸脱氢酶在中晚期肝细胞癌靶向及免疫治疗中的预后预测价值研究

The prognostic value of serum lactate dehydrogenase level as a predictor of prognosis in targeted therapy and immunotherapy for advanced hepatocellular carcinoma

:446-452
 
      目的 探讨血清乳酸脱氢酶(LDH)在中晚期肝癌患者接受靶向联合免疫治疗后的预后预测价值。方法 选取2022年1月—2024年8月在莆田学院附属医院肿瘤内科经病理和影像学检查确诊的中晚期肝癌患者作为研究对象。从医院的电子病历系统中收集患者的基线资料,随访截止2025年8月,并记录随访结果,包括患者的疾病缓解情况和死亡情况,以及无疾病进展生存期(PFS)、总生存期(OS)。采用Kaplan-Meier方法绘制不同基线LDH水平患者的OS生存曲线,并通过Log-rank检验比较生存曲线。同时,运用多因素Cox比例风险回归分析探讨影响中晚期肝癌患者在接受靶向联合免疫治疗后OS的相关因素。结果 结果显示,在50例肝癌患者中,基线LDH低于200 U/L的有15例,而高于200 U/L的有35例。与基线LDH<200 U/L组相比,基线 LDH≥200 U/L患者PFS、OS更短,差异均有统计学意义(χ2分别为5.51、15.6,P值分别为0.019、0.017)。治疗8周后,与LDH降低患者相比,LDH升高患者OS更短,差异有统计学意义(χ2=13.2,P=0.04)。多因素Cox比例风险回归分析结果表明,基线LDH水平超过200 U/L是中晚期肝癌患者接受靶向联合免疫治疗后OS的影响因素[P=0.035,HR(95%CI)=5.03(1.12,22.54)]。结论 基线LDH水平较低的患者表现出更好的OS。基线LDH水平可以作为预测中晚期肝癌患者在接受靶向联合免疫治疗时预后的指标。 
   Objective To evaluate the prognostic significance of serum lactate dehydrogenase(LDH)levels in patients with advanced hepatocellular carcinoma(HCC)undergoing targeted therapy combined immunotherapy.Methods Patients diagnosed with advanced HCC were selected in Putian College Affiliated Hospital from January 2022 to August 2024,diagnosed with pathological and imaging examinations results.Patient baseline data were collected from the hospital’s electronic medical records,with follow-up extending until August 2025.We documented outcomes such as disease response and mortality,along with progression-free survival(PFS)and overall survival(OS).Kaplan-Meier survival curves were constructed based on baseline LDH levels,and the Log-rank test was employed for comparison.Additionally,multivariate Cox proportional hazards regression analysis was conducted to identify factors influencing OS in patients receiving targeted therapy combined immunotherapy.Results Among the 50 patients,15 had baseline LDH levels below 200 U/L,while 35 had levels above.Patients with baseline LDH≥200 U/L had significantly shorter PFS and OS than those with baseline LDH <200 U/L(χ2=5.51 and 15.6 for PFS and OS,respectively;P=0.019 and 0.017,respectively).After 8 weeks of treatment,patients with increased LDH had significantly shorter OS compared with patients with decreased LDH(χ2=13.2,P=0.04).Multivariate Cox proportional hazards regression analysis indicated that a baseline LDH level exceeding 200 U/L is an independent prognostic factor for OS in patients with intermediate to advanced HCC receiving targeted therapy combined with immunotherapy(P=0.035,HR 5.03[1.12,22.54]).Conclusions Patients with lower baseline LDH levels demonstrated better OS,suggesting that baseline LDH can serve as an important prognostic indicator for advanced HCC patients undergoing targeted combined immunotherapy.
论著

GRB14 基因在肺腺癌中的表达及对预后的影响

Expression and clinical significance of GRB14 in lung adenocarcinoma

:1482-1490
 
       目的   初步探讨生长因子受体结合蛋白14(GRB14)在肺腺癌患者预后中的具体作用机制。方法   通过TIMER数据库、UALCAN数据库及GEPIA数据库,探讨GRB14 mRNA在肺腺癌及正常肺组织中的表达。运用免疫组织化学通过组织芯片(75例肺腺癌患者和75例癌旁组织)检测其蛋白表达水平,收集国外肿瘤研究团队上传至TCGA数据库229例肺腺癌患者的临床数据,分析评估GRB14在肺腺癌患者的表达及其临床特征及生存预后之间的关系。应用TIMER数据库对GRB14肺腺癌患者进行免疫浸润分析。String数据库探讨GRB14与其他蛋白之间是否存在相互作用。结果  TIMER数据库分析显示,相比正常组织,GRB14 mRNA在多种实体肿瘤和肺腺癌组织中高表达(P<0.05)。使用UALCAN数据库和GEPIA数据库以正常样本为对照组,肺腺癌患者的GRB14的表达均增加(P<0.01)。免疫组织化学检测组织芯片结果显示,GRB14蛋白在肺腺癌的表达高于正常肺组织(肺腺癌6.07±1.01 vs 癌旁组织4.80±1.22;P<0.01)。TCGA数据库分析显示,肺腺癌患者中GRB14高表达组和低表达组的中位总生存期分别为(41.59±5.20)月和(88.67±16.69)月;结合TCGA数据库绘制ROC曲线,发现GRB14的表达对肺腺癌患者具有一定的诊断价值。单因素回归分析结果显示,肿瘤分期(Ⅲ-Ⅳ)(P<0.01)、肿瘤原发灶的情况(T3-4)(P<0.01)、淋巴结转移(N1-3)(P<0.01)和GRB14表达(P<0.01)是影响肺腺癌中位总生存期的因素;Cox多因素回归分析显示,淋巴结转移(N1-3)(P<0.05)和GRB14表达P<0.01)是影响肺腺癌中位总生存时间的因素。TIMER数据库分析显示,GRB14 mRNA 表达与巨噬细胞(r=-0.164,P<0.01)、中性粒细胞(r=-0.175,P<0.01)和树突状细胞(r=-0.148,P<0.01)具有相关性。通过String数据库分析发现与GRB14相互作用的蛋白质包括EGFR、HRAS、FGFR1、INSR、CNGA1、COBLL1、LYPLAL1、TNKS2、TNKS、PRKCZ。结论  GRB14表达增加与肺腺癌患者预后不良相关。
       Objective  To assess the specific mechanism of growth factor receptor-bound protein 14(GRB14)in the prognosis of lung adenocarcinoma(LUAD)patients.Methods  The expression of GRB14 mRNA in LUAD and normal lung tissue was explored using TIMER database,UALCAN database,and GEPIA database.The expression of GRB14 protein was examined by immunohistochemistry using a tissue microarray.Then,the associations of GRB14 expression with clinicopathological features and clinical outcomes of LUAD were validated by analyzing TCGA database at the mRNA level and statistically evaluating the results.TIMER database was used to analyze immune infiltration of GRB14 in LUAD.Protein-protein interaction of GRB14 were analyzed using the String database.Results  Using the TIMER database,we found that GRB14 mRNA was highly expressed in various solid tumors and LUAD tissues compared to normal tissues(P<0.05).Comparing with the normal group,the expression of GRB14 was increased in LUAD(P<0.01)via using UALCAN database and GEPIA database.The expression level of GRB14 protein in the LUAD tissues was significantly higher than that in the noncancerous LUAD tissues(LUAD[6.07±1.01] vs benign,[4.80±1.22];P<0.01)in tissue microarray .Median overall survival in the high and low GRB14 expression groups in LUAD was(41.59±5.2)and(88.67±16.69)months respectively.We plotted the ROC curves of 3-year survival rate and 5-year survival rate which again suggested that the model had good predictive performance.Univariate analysis revealed that individual cancer stages(Ⅲ-IV)(P<0.01),tumor(T3-4)(P<0.01),lymph node metastasis(N1-3)(P<0.05)and GRB14 expressionP<0.01)were risk factors affecting the median overall survival time of LUAD.According to Cox multiple regression analysis,we found that lymph node metastasis(N1-3)(P<0.05)and GRB14 expression(P<0.01)were  risk factors affecting the median overall survival time of LUAD.Using TIMER database analysis,the mRNA level of GRB14 was significantly correlated with macrophages(r=-0.164,P<0.01),neutrophils(r=-0.175,P<0.01)and dendritic cells(r=-0.148,P<0.01).Through analysis of the String database,it was found that proteins that interacted with GRB14 including EGFR,HRAS,FGFR1,INSR,CNGA1,COBLL1,LYPLAL1,TNKS2,TNKS,PRKCZ.Conclusions  The results of the present study suggest that GRB14 may efficiently predict poor survival in LUAD patients.
论著

化疗联合NKG2A抑制剂抗头颈部鳞状细胞癌作用的研究

Effect of chemotherapy combined with NKG2A inhibitor on head and neck squamous cell carcinoma

:860-868
 
目的 研究靶向NKG2A抑制剂抗头颈部鳞状细胞癌(HNSCC)的作用。方法 应用GEO和TCGA数据库分析NKG2A及其配体HLA-E单细胞表达情况、与患者预后以及免疫微环境的相关性。构建HNSCC皮下抑制瘤模型,流式细胞技术检测化学治疗(化疗)对免疫检测点NKG2A表达的影响。动物实验验证NKG2A抑制剂以及NKG2A抑制剂联合多西他赛化疗的抗肿瘤作用。结果 NKG2A(KLRC1)主要表达在NK细胞,少量表达在T淋巴细胞。HNSCC肿瘤高表达NKG2A/HLA-E(P<0.01),与患者不良预后密切相关;肿瘤微环境中NKG2A/HLA-E与多个免疫细胞浸润以及免疫检测点表达密切相关(P<0.01)。动物实验显示化疗能上调T、B淋巴细胞表达免疫检查点NKG2A的表达水平(P<0.01);化疗的基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用(P=0.013)。结论 化疗基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用,为探索HNSCC临床新策略提供实验和理论基础。
Objective To investigate the anti-tumor effects of NKG2A inhibitor on head and neck squamous cell carcinoma(HNSCC).Methods The single-cell expression of NKG2A ,its ligand HLA-E and their correlations with patient prognosis and immune microenvironment were analyzed in GEO and TCGA databases.The subcutaneous tumor model of HNSCC was constructed,and the effects of chemotherapy on the expression of NKG2A on T and B lymphocytes were detected by flow cytometry.Animal experiments were used to confirmed the anti-tumor effects of NKG2A inhibitor and NKG2A inhibitors combined with docetaxel.Results NKG2A(KLRC1)was mainly expressed in NK cells,and a small amount was expressed in T lymphocytes.The high expression of NKG2A/HLA-E in HNSCC tumors(P<0.01)were closely related to poor prognosis.NKG2A/HLA-E in tumor microenvironment were closely related to the infiltration of multiple immune cells and the expression of immune checkpoints(P<0.01).Animal experiments showed that chemotherapy could up-regulate the expression of NKG2A in T and B lymphocytes(P<0.01).Chemotherapy in combination with NKG2A inhibitor could mediate more effective antitumor effects in HNSCC(P=0.013).Conclusions Combined with NKG2A inhibitor on the basis of chemotherapy can mediate more effective anti-tumor effects,and this study may provide experimental and theoretical basis for exploring new clinical strategies of HNSCC.
论著

CT、MRI影像学表现对原发性肝细胞癌微血管侵犯的诊断价值

Diagnostic value of CT and MRI imaging manifestations for microvascular invasion in primary hepatocellular carcinoma

:681-688
 
目的 探讨CT、MRI影像学表现对原发性肝细胞癌(HCC)微血管侵犯(MVI)的诊断价值。方法 选取2018年1月—2024年7月江门市第二人民医院(江门市中心医院蓬江分院)和江门市中心医院120例(共158个病灶)HCC患者,均行上腹部CT、MRI平扫+增强及弥散加权成像(DWI)检查;以术后病理结果为金标准。比较CT、MRI平扫+增强及DWI对HCC MVI诊断效能;分析HCC MVI诊断中CT、MRI平扫+增强及DWI检查与术后病理确诊结果之间的一致性;比较HCC MVI与无HCC MVI患者影像学表现及表观扩散系数(ADC)值。结果 DWI检查对HCC MVI的诊断效能(灵敏度、特异度、准确度、阳性预测值、阴性预测值)均显著性高于CT、MRI平扫+增强(P<0.05);CT、MRI、DWI对原发性肝细胞癌患者微血管侵犯的诊断效能比较,差异均无统计学意义(P>0.05)。在HCC MVI诊断效能中,CT、MRI影像学表现与术后病理确诊结果之间为中度一致性;DWI与术后病理确诊结果之间为高度一致性。HCC MVI患者的强化方式在非边缘动脉期强化、强化包膜、晕状强化、结中结、门脉分支癌栓占比均显著性高于无HCC MVI患者(P<0.05)。在不同b值(400、800、1 000、1 500 s/mm2)下,HCC MVI患者的ADC值均显著性高于无HCC MVI患者(P<0.05)。结论 CT、MRI平扫+增强及DWI对HCC MVI均具有较好的诊断效能,而MRI诊断结果与病理诊断一致性更佳,尤其DWI图中ADC值可更加精准地判断HCC的患者是否发生微血管侵犯,有助于指导临床医生建立“个体化”精准诊疗策略。
Objective To explore the diagnostic value of CT and MRI imaging manifestations for microvascular invasion(MVI)in primary hepatocellular carcinoma(HCC).Methods A total of 120 patients(158 lesions in total)with HCC in the Second People’s Hospital of Jiangmen(Pengjiang Branch of Jiangmen Central Hospital)and Jiangmen Central Hospital were selected from January 2018 to July 2024,all underwent CT and MRI plain + enhanced and diffusion-weighted imaging(DWI)of the upper abdomen;postoperative pathology Results was used as the diagnostic gold standard.The diagnostic efficacy of CT,MRI plain + enhanced and DWI for HCC MVI was compared.The concordance among CT,MRI plain + enhanced and DWI examinations with postoperative pathological diagnostic findings in the diagnosis of HCC MVI.Imaging manifestations and apparent diffusion coefficient(ADC)values in patients with and without HCC MVI were compared.Results Diagnostic effectiveness of DWI examination for HCC MVI(sensitivity,specificity,accuracy,positive predictive value,negative predictive value)were all significantly higher than those of CT and MRI plain + enhanced(P<0.05);none of the differences were statistically significant(P>0.05)in the comparison of diagnostic effectiveness of CT,MRI,and DWI for the diagnosis of MVI in patients with primary HCC.In HCC MVI diagnostic effectiveness,moderate concordance was found among CT,MRI imaging phenotypes and postoperative pathology Results;high concordance was found between DWI and postoperative pathology Results.In HCC MVI patients,the proportion of non-marginal arterial reinforcement,enhanced envelope,halo reinforcement,nodal in nodal and portal branch cancer thrombi was significantly higher than that in patients without HCC MVI(P<0.05).At different b-values(400,800,1 000,1 500 s/mm2),ADC values were all significantly higher in patients with HCC MVI than in patients without HCC MVI(P<0.05).Conclusions CT,MRI plain + enhanced and DWI have good diagnostic effectiveness for HCC MVI,while MRI diagnostic Results are in better concordance with pathologic diagnosis.In particular,ADC values in DWI maps can more accurately determine whether MVI occurs in patients with HCC,which helps to guide clinicians to establish“individualized”and precise diagnosis and treatment strategies.
论著

LINC02038与子宫内膜癌发生、发展的关联性分析

Association analysis of LINC02038 with endometrial carcinoma progression

:18-24
 
目的 分析长链非编码RNA LINC02038的表达与子宫内膜癌发生、发展的关联性,并探讨其潜在的生物学调控机制,为子宫内膜癌的精准诊治提供科学线索。方法 采用荧光定量PCR技术检测LINC02038 在2019年—2020年期间于我院收集的42例子宫内膜癌标本及相应癌旁正常组织中的表达差异。构建LINC02038过表达载体并转染子宫内膜癌Ishikawa 细胞系,通过CCK-8、Transwell等功能实验验证其对肿瘤细胞增殖、侵袭能力的影响。利用TCGA公共数据库分析LINC02038与子宫内膜癌预后的相关性,并通过基因本体论(GO)、京都基因组百科全书(KEGG)及基因集富集分析(GSEA)等生物信息学方法预测其潜在的下游调控机制。结果 LINC02038在子宫内膜癌组织中的表达高于癌旁正常组织(P<0.001)。过表达LINC02038可促进子宫内膜癌细胞Ishikawa的增殖和迁移。生物信息学分析提示LINC02038可能通过调控细胞分化、激素分泌、细胞外基质重塑等过程,激活NF-κB、细胞外基质受体等信号通路影响子宫内膜癌的发生。结论 LINC02038的异常表达与子宫内膜癌的发生、发展相关联,可作为评估子宫内膜癌发病风险的候选生物标志物。
Objective To analyze the expression of long non-coding RNA LINC02038 and its relationship with the occurrence and development of endometrial carcinoma(EC),explore its potential biological mechanisms,and provide potential biomarkers for targeted therapy of EC.Methods Quantitative real-time PCR was used to detect the expression levels of LINC02038 in 42 EC tissues and their adjacent tissues.The LINC02038 overexpressin vector was constructed and transfected into EC Ishikawa cells.CCK-8,Transwell migration and invasion assays were performed to examine the effects of LINC02038 overexpression on cancer cell proliferation,migration and invasion.Public TCGA data were analyzed to investigate the associations between LINC02038 and EC pathogenesis and prognosis.GO,KEGG and GSEA enrichment analyses were conducted to elucidate the potential biological mechanisms of LINC02038.Results LINC02038 expression was significantly upregulated in EC tissues compared to adjacent non-tumor tissues(P<0.001).Overexpression of LINC02038 markedly promoted the proliferation and migration of Ishikawa cells.Bioinformatics analysis suggested that LINC02038 may participate in regulating cell differentiation,hormone secretion,extracellular matrix remodeling and other processes,as well as activating NF-κB,extracellular matrix receptor and other signaling pathways involved in endometrial carcinogenesis.Conclusions The aberrant expression of LINC02038 is associated with EC occurrence and may serve as a potential biomarker for assessing the risk of this cancer.
综述

食欲症状在肝癌营养不良患者中的研究进展

Progress of appetite symptoms in malnourished patients with hepatocellular carcinoma

:585-590
 
肝癌患者因食欲降低、进食减少导致不同程度的营养不良,引发厌食症,甚至恶病质,严重影响患者生存质量。食欲评估是降低营养风险的基础,医护人员可通过食欲症状的评估调整患者饮食及营养指导措施,以改善患者营养状态,提高生存质量。该文对食欲的评估工具、方法及干预在肝癌营养不良患者中的应用现状进行阐述,为肝癌患者的食欲干预提供科学依据。
Hepatocellular carcinoma patients suffer from different degrees of malnutrition due to decreased appetite and eating,which triggers anorexia and even cachexia,seriously affecting the quality of patient survival.Appetite assessment is the basis for reducing nutritional risk,and healthcare professionals can adjust patients’ diet and nutritional guidance measures through the assessment of appetite symptoms in order to improve patients’ nutritional status and survival quality.In this paper,the current status of the assessment tools,methods and interventions of appetite in malnutrition patients with hepatocellular carcinoma are described to provide a scientific basis for appetite interventions.
论著

SP免疫组化染色检测IGF-1及组织P53蛋白的表达在结直肠腺癌中意义

The significance of SP immunohistochemical staining for detecting the expression of IGF-1 and tissue P53 in colorectal adenocarcinoma

:1269-1274
 
目的 探讨链霉菌抗生物素蛋白-过氧化物酶(SP)免疫组化染色检测胰岛素样生长因子-1(IGF-1)及组织P53蛋白的表达在结直肠腺癌中意义。方法 选取乌鲁木齐市中医医院2020年1月—2023年12月收治的169例结直肠腺癌患者为恶性组,另选取我院同期收治的169例良性结直肠肿瘤患者为良性组。取手术或活检病理组织应用SP免疫组化染色检测2组肿瘤组织IGF-1及P53蛋白表达水平,对比良性组与恶性组间差异,分析不同临床分期、淋巴结转移情况及组织分化程度患者的IGF-1水平、IGF-1mRNA及P53蛋白阳性率。结果 SP免疫组化染色检测IGF-1阳性率、P53蛋白阳性率,恶性组(72.78%、47.93%)均高于良性组(14.79%、6.51%),对比差异有统计学意义(χ2=115.440、χ2=73.180,P<0.05);Ⅳ期患者IGF-1阳性率(96.77%)及P53蛋白阳性率(77.42%)高于Ⅲ期(85.11%、63.83%)、Ⅱ期(62.69%、31.34%)及Ⅰ期患者(45.83%、25.00%),对比差异有统计学意义(χ2=24.860,χ2=28.000,P<0.05),各亚组两两比较差异无统计学意义(IGF-1阳性与阴性,Ⅰ期 vs Ⅲ期,χ2=12.110,P<0.001;Ⅰ期 vs Ⅳ期,χ2=16.060,P<0.001;Ⅱ期 vs Ⅲ期,χ2=6.880,P=0.009;P53蛋白阳性与阴性Ⅰ期 vs Ⅲ期,χ2=9.580,P<0.002;Ⅰ期 vs Ⅳ期,χ2=14.9990,P<0.001;Ⅱ期 vs Ⅲ期,χ2=11.790,P=0.001;);有淋巴结转移患者IGF-1阳性率(85.71%)及P53蛋白阳性率(71.43%)高于无淋巴结转移患者(14.79%、40.94%),对比差异有统计学意义(χ2=4.720、11.740,P<0.05);低分化患者IGF-1阳性率(93.48%)及P53蛋白阳性率(71.74%)高于中分化患者(81.18%、54.12%)、高分化患者(52.63%、31.58%),对比差异有统计学意义(χ2=21.250、13.510,P<0.05)。结论 SP免疫组化染色检测提示结直肠腺癌患者IGF-1、P53蛋白阳性率高于良性肿瘤患者,且临床分期高、淋巴结转移与肿瘤组织低分化者的IGF-1、P53蛋白阳性率高,因此IGF-1、P53有望成为结直肠腺癌诊治的重要检测指标。
Objective Exploring the significance of immunohistochemical staining with streptavidin-perosidase(SP)to detect the expression of insulin-like growth factor-1(IGF-1)and tissue P53 in colorectal adenocarcinoma.Methods A total of 169 patients with colorectal adenocarcinoma admitted to a hospital from January 2020 to December 2023 were selected and divided into the malignant group.Other 169 patients with benign colorectal tumors admitted to a hospital during the same period were selected and divided into the benign group.SP immunohistochemistry staining was used to detect and compare the expression levels of IGF-1 and P53 proteins in two groups of tumor tissues obtained in surgery or biopsy.And the IGF-1 levels,IGF-1 mRNA,and P53 positivity rates in patients with different clinical stages,lymph node metastasis,and tissue differentiation levels were compared.Results There was a significant difference in the positive rates of IGF-1mRNA and P53 detected by SP immunohistochemistry staining,and malignant group(72.78%,47.93%)were higher than the benign group(14.79%,6.51%),which were statistically significant(χ2=115.440,73.180,P<0.05).The positive rates of IGF-1 and P53 were 96.77% and 77.42% in stage IV,which were higher than those in Stage III(85.11%,63.83%),II(62.69%,31.34%)and I(45.83%,25.00%),the differences were statistically significant(χ2=24.860,28.000,P<0.05).The expression levels of IGF-1 and P53 in colorectal adenocarcinoma patients with different lymph node metastases showed significant differences,the positive rates of IGF-1(85.71%)and P53(71.43%)in patients with lymph node metastasis were higher than those without lymph node metastasis(14.79%,40.94%),and the differences were statistically significant(χ2=4.720,11.740,P<0.05).There were significant differences in the expression levels of IGF-1 and P53 among patients with colorectal adenocarcinoma of different degrees of differentiation,the positive rates of IGF-1(93.48%)and P53(71.74%)were significantly higher than those of moderately differentiated(81.18%,54.12%)and well differentiated(52.63%,31.58%),and the differences were statistically significant(χ2=21.250,13.510,P<0.05).Conclusion sThrough SP immunohistochemical staining,it was found that the positivity rates of IGF-1 and P53 in colorectal adenocarcinoma patients were higher than those in benign tumor patients,and those with high the clinical stage,lymph node metastasis,and low differentiation of tumor tissue,had higher the positivity rates of IGF-1 and P53.Therefore,IGF-1 and P53 are expected to become important monitoring indicators for the diagnosis and treatment of colorectal adenocarcinoma.
论著

SNHG12在乙肝病毒X蛋白诱导肝癌发生中的作用研究

Study on the role of SNHG12 in the occurrence of hepatocarcinoma induced by hepatitis B virus X protein

:16-24
 
目的 探究长链非编码RNA SNHG12在乙肝病毒X蛋白(HBx)诱导肝癌发生过程中的作用。方法 把课题组构建的肝前体细胞14-19、EGFP-14-19、HBx-EGFP-14-19通过小鼠肝门静脉注射到体内;采用 qRT-PCR、Western blot 方法检测30 d,90 d,180 d,360 d小鼠肝脏组织及细胞模型中HBx、SNHG12以及下游调节基因的mRNA和蛋白表达情况;使用si-SNHG12干扰其表达,并通过CCK-8、划痕实验、transwell实验、流式细胞术观察其对体外表型影响;检测SNHG12及下游的 mRNA 和蛋白表达;HE染色观察小鼠肝组织切片。结果 qRT-PCR结果表明SNHG12、Notch1、Hes1在HBx-EGFP-14-19细胞及各时间段的小鼠肝组织中均上调(F=48.808,P<0.000 1;F=13.322,P<0.000 1);Western blot结果显示在HBx过表达细胞及动物模型中,受HBx诱导SNHG12表达升高后Notch1信号通路被激活,促凋亡因子Bax下调,抗凋亡因子Bcl-2上调,细胞周期因子CDK2和Cyclin E上调;抑制SNHG12表达后,qRT-PCR、Western blot实验结果显示SNHG12(t=22.746,P<0.000 1)及其上述基因表达均扭转,CCK-8实验显示细胞增殖受到明显抑制,流式细胞术检测显示细胞凋亡增多,划痕及transwell实验表明细胞迁移及侵袭减弱。结论 HBx通过上调SNHG12诱导Notch1表达,导致细胞增殖、周期和凋亡异常,从而促进肝癌的发生。
Objective In order to explore the role of long non-coding RNA SNHG12 in hepatitis B virus X protein (HBx) induced hepatocarcinogenesis. Methods The liver precursor cells 14-19, EGFP-14-19 and HBx-EGFP-14-19 constructed by the research group was injected into the body through the hepatic portal vein of KM mice; qRT-PCR and Western blot were used to detect the mRNA and protein expression of HBx, SNHG12 and downstream regulatory genes in liver tissues of 30 d, 90 d, 180 d and 360 d mice and cell models. Si-SNHG12 was used to interfere with SNHG12 expression in vitro, the mRNA and protein expression of SNHG12 and downstream genes were detected, and its effect on phenotype in vitro was observed by CCK-8, flow cytometry, scratch test and transwell test. HE staining was used to observe the liver sections of mice. Results qRT-PCR showed that SNHG12, Notch1 and Hes1 were up-regulated in HBx overexpression cells and mouse liver tissue at each time point (F=48.808,P<0.000 1;F=13.322,P<0.000 1); the results of Western blot showed that in HBx over-expressing cells and animal models, the expression of SNHG12 was increased induced by HBx, resulting in the activation of Notch1 signal pathway, the down regulation of pro-apoptotic factor Bax, anti-apoptotic factor Bcl-2, and the up-regulation of cell cycle factors CDK2, cyclin E. After inhibiting the expression of SNHG12, the results of qRT-PCR and Western blot showed that SNHG12 (t=22.746,P<0.000 1) and the above genes were inhibited; CCK-8 experiment showed that cell proliferation was significantly inhibited, flow cytometry showed that cell apoptosis increased, scratch experiment and transwell experiment showed that cell migration and invasion decreased. Conclusions HBx induced Notch1 expression by up regulating SNHG12, resulting in abnormal cell proliferation, cycle and apoptosis, so as to promote the occurrence of liver cancer.
论著

化疗联合调强放疗治疗老年(≥65岁)局部晚期鼻咽癌的临床疗效

Clinical efficacy of chemotherapy combined with intensity-modulated radiotherapy in the treatment of elderly(≥65 years old)locally advanced nasopharyngeal carcinoma

:40-44
 
目的 探析化疗联合调强放疗(IMRT)治疗老年(≥65岁)局部晚期鼻咽癌的临床效果。方法 选取2018年1月—2019年1月我院诊治的90例老年局部晚期鼻咽癌患者为研究对象,使用随机数表法将此90例患者分为观察组及对照组,各45例。观察组行IMRT,对照组行化疗联合IMRT,对比2组的效果。结果 2组的治疗总有效率均为100%,组间差异不显著(P<0.05)。观察组的生活质量改善率(93.33%)高于对照组(77.78%)(P<0.05)。对照组出现3~4级白细胞减少、呕吐、黏膜炎人数明显高于观察组(P<0.05),两者其他毒副反应比较无显著差异(P>0.05)。观察组的1年总体生存率(91.11%)及3年总体生存率(75.56%)均高于对照组(86.67%、68.89%)(P<0.05)。结论 对于老年局部晚期鼻咽癌,化疗联合IMRT相比单纯IMRT降低了远期生存率,增加了毒副反应并影响疗后生活质量的改善,不宜常规应用,单纯IMRT可能是更合适的治疗选择。
Objective To explore the clinical effect of chemotherapy combined with intensity modulated radiation therapy(IMRT)in the treatment of elderly(≥65 years old)locally advanced nasopharyngeal carcinoma.Methods The study was carried out from January 2018 to January 2019.During this period,90 elderly patients with locally advanced nasopharyngeal carcinoma who were diagnosed and treated in our hospital were selected as the research objects.The random number table method was used to divide the 90 patients into observation groups,and the control group,each with 45 cases.The observation group was treated with IMRT,and the control group was treated with chemotherapy combined with IMRT.The effects of the two groups were compared.Results The total effective rate of the two groups was 100%,and there was no significant difference between the two groups(P<0.05).The improvement rate of quality of life in the observation group(93.33%)was higher than that in the control group(77.78%,P<0.05).The number of grade 3-4 leukopenia,vomiting and mucositis in the control group was significantly higher than that in the observation group(P<0.05),and there was no significant difference in other side effects between the two groups(P>0.05).The 1-year overall survival rate(91.11%)and 3-year overall survival rate(75.56%)of the observation group were higher than those of the control group(86.67%,68.89%,P<0.05).Conclusions For locally advanced nasopharyngeal carcinoma in the elderly,chemotherapy combined with IMRT reduces the long-term survival rate,increases the toxic and side effects and affects the improvement of the quality of life after treatment.It is not suitable for routine application,and IMRT alone may be a more appropriate treatment choice.
论著

MSCT增强扫描期相及VOI的选择在基于影像组学方法预测原发性肝细胞癌微血管侵犯中的价值

The value of contrast-enhanced MSCT with phases and VOI strategies in the prediction of microvascular invasion in primary hepatocellular carcinoma based on radiomics

:36-43
 
目的 基于影像组学方法,探讨多层螺旋CT(MSCT)四期增强扫描单一/不同期相及不同容积感兴趣区(VOI)的选择,在术前预测原发性肝细胞癌(HCC)微血管侵犯(MVI)中的价值。方法 回顾性收集88例经手术病理证实为HCC并行术前MSCT四期增强扫描的患者,其中包括47例MVI阳性患者和41例MVI阴性患者。在MSCT增强扫描的动脉早期、动脉晚期、门静脉期及延迟期图像中手动逐层勾画肿瘤ROI,获得瘤体容积感兴趣区VOI(Vt),然后基于计算机自动膨胀算法将Vt外扩10 mm获得瘤体及瘤周VOI(Vt+Vp)。使用Pyradiomics软件分别从Vt和Vt+Vp中提取影像组学特征,随后采用15种特征选择方法和10种分类器构建150个预测模型,并通过十折交叉检验以验证模型的效能。使用准确度、敏感度、特异度、受试者工作特性曲线下面积(AUC)评估模型的效能,并比较性能最优的前三个预测模型。结果 MSCT四期增强扫描图像中预测HCC MVI状态的影像组学模型在门静脉期的表现优于其它期相及各期相的不同组合,其中最大的AUC值在Vt和Vt+Vp两种ROI中分别为0.768和0.782。此外,基于Vt+Vp的影像组学模型对MVI的预测效能优于基于Vt的影像组学模型,基于Vt+Vp性能最优的预测模型的AUC值、准确度、敏感度和特异度分别0.782、0.728、0.745和0.705。结论 采用影像组学方法术前无创性预测HCC MVI状态首选增强扫描的门静脉期,ROI首选瘤体联合瘤周10 mm区域。
Objective To investigate the value of single or different phases of contrast-enhanced multi-slice spiral CT(MSCT)in different volumetric regions of interest(ROI)to preoperatively predict the state of microvascular invasion in primary hepatocellular carcinoma(HCC)based on radiomics methods.Methods A total of 88 patients with HCC confirmed by surgical pathology who underwent preoperative MSCT quadruple-enhanced scan were retrospectively recruited,including 47 MVI-positive patients and 41 MVI-negative patients.The ROI was manually delineated slice-by-slice in the early arterial phase,late arterial phase,portal venous phase,and equilibrium phase of enhanced MSCT images to obtain the volume of tumor VOI(Vt),and then Vt was expanded by 10 mm through the computer expansion algorithm automatically to obtain the volume of tumor and peritumor(Vt+Vp).Pyradiomics software was used to extract radiomic features from Vt and Vt+Vp,followed by 150 discriminant models constructed with 150 feature selection methods and 10 classifiers,and then 10-fold cross-validation was used to evaluate the performance of these models.Using accuracy,sensitivity,specificity,area under the receiver operating characteristic curve(AUC)to assess model performance.The top three predictive models with the best performance were also compared.Results The radiomics model for predicting HCC MVI status in portal venous phase among quadruple-enhanced MSCT images outperformed other phases and different combinations of phases,achieving the highest AUC values of 0.768 and 0.782 in Vt and Vt+Vp respectively.In addition,the prediction performance of the radiomics model based on Vt+Vp was superior to models based on Vt.AUC value,accuracy,sensitivity,and specificity of the model with the best performance based on Vt+Vp were 0.782,0.728,0.745 and 0.705 respectively.Conclusions Radiomics models based on the portal venous phase of contrast-enhanced MSCT and tumor combined with the 10mm peritumoral area were more recommended to be employed to preoperative non-invasively predict the state of HCC MVI.
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