NSUN5, also known as NOP2/Sun domain 5, is a pivotal RNA methyltransferase that catalyzes the formation of 5-methylcytosine (m5C). Cuproptosis, induced by elevated copper concentrations, is under investigation as a potential therapeutic strategy for cancer treatment. Despite this, the specific roles and the molecular mechanisms underlying Cuproptosis and NSUN5-mediated m5C modification in cholangiocarcinoma (CCA) remain to be fully elucidated. Human tissue samples were collected to assess the expression levels of NSUN5 in CCA. In vitro functional assays were conducted to evaluate the biological function of NSUN5. The functional mechanism of NSUN5 on glutaminase (GLS) was investigated using RNA pull-down, RNA immunoprecipitation, molecular docking, and RNA stability assays. This study identified an upregulation of NSUN5 in CCA tissues. The knockdown of NSUN5 diminished the proliferation, migration, and invasion capabilities of CCA cells in vitro. In contrast, the overexpression of NSUN5 enhanced the growth and metastasis of CCA cells. Additionally, an increased copper content was detected in CCA tissues, which correlated with aggressive clinical features. CCA cells exhibited resistance to cuproptosis by upregulating GLS expression. Functionally, NSUN5 was found to positively modulate GLS expression. The NSUN5-mediated m5C modification at site 137 C on the GLS mRNA sequence stabilizes the GLS mRNA, leading to an accumulation of GLS within cells. Our findings highlight the critical role of NSUN5 in CCA progression through m5C-dependent stabilization of the GLS transcript, suggesting a potential targeted therapeutic strategy for CCA.
Background:Despite the high incidence of lateral neck lymph node (LN) metastasis in papillary thyroid cancer (PTC), the management of the lateral neck remains controversial. We aimed to map the draining LNs in the lateral neck using carbon nanoparticles and explore its potential in neck evaluation.Methods:We conducted a multicenter, prospective study in PTC patients who had non-palpable yet suspicious metastatic lateral LNs on ultrasound and/or computed tomography (CT) but could not be confirmed by fine needle aspiration. Carbon nanoparticle suspension was injected peritumorally into the thyroid and modified lateral neck dissection was subsequently performed.Results:A total of 154 patients were enrolled for analysis. And 5,070 lateral LNs were removed, of which 1,079 (21.3%) were dyed. The median of dyed LNs was 6 per case (range, 1-33). The distribution of dyed LNs in neck compartments was IV > III > IIA > IIB/V, independent of tumor size, location, multifocality or microscopic extra-thyroidal extension (ETE). Compared with undyed LNs, the probabilities of metastasis in dyed LNs were significantly increased in compartment III, IV, V, and II-V (III: 29.3% vs. 15.4%, P<0.001; IV: 26.3% vs. 14.5%, P<0.001; V: 16.7% vs. 3.3%, P=0.005; II-V: 26.3% vs. 10.0%, P<0.001). The relative risks of metastasis in dyed LNs compared with undyed LNs were 1.90, 1.82, 5.04 and 2.62 in compartment III, IV, V, and II-V, respectively.Conclusions:It was the first prospective multicenter study to map the lateral neck LNs with carbon nanoparticles, which could help surgeons visualize the suspicious LNs during surgery. Instead of unguided LN biopsy, this method has a potential role in lateral neck assessment for indeterminate lateral LNs in PTC.
Objective:To analyze the relationship between the expression of long noncoding RNA LINC00673 and clinicopathological features of patients with colon cancer and its molecular mechanism.Methods:The expression of LINC00673 in 70 cases of colon cancer and adjacent normal intestinal mucosa was detected by real-time quantitative polymerase chain reaction (Real-time PCR). and all data was collected in Second Hospital of Hebei Medical University from April, 2017 to June, 2019. There were 45 males and 25 females were enrolled in this study, and age was (56.4±11.8) years, median age 56 year. The relationship between LINC00673 expression and clinicopathological features of patients was analyzed. RNA interference technique was used to silence the expression of LINC00673 in colon cancer cells, and the effect of the LINC00673 down-expression on cell epithelial-mesenchymal transition (EMT) and its molecular mechanism were studied.SPSS22.0 statistical software was used to analyze the data, and t-test and ANOVA were used to investigate the data. Results:The expression of LINC00673 in colon cancer tissues (1.393±0.345) was significantly higher than that in adjacent normal intestinal mucosa tissues (0.703±0.223) ( t=14.053, P<0.01). The expression of LINC00673 was correlated with the degree of differentiation (well differentiated 1.004±0.273, poorly differentiated 1.491±0.245), clinical stage (Ⅰ-Ⅱ: 1.009±0.274, Ⅲ-Ⅳ: 1.608±0.226) and lymph node metastasis (positive 1.523±0.265, negative 0.988±0.290) ( t=-6.084, P<0.01; t=-9.730, P<0.01; t=6.060, P<0.01). The level of LINC00673 in colon cancer cell lines was significantly higher than that in normal intestinal mucosa cell line HIEC ( F=21.364, P<0.01). The ability of cell migration and invasion was significantly decreased after silencing the expression of LINC00673 in LOVO ( F=1 211.220, 72.672, P<0.01). The expression of E-Cadherin in cells was increased, and the expression of N-Cadherin, Vimentin and matrix metalloproteinase (MMP)-9 was significantly decreased ( F=196.401, 147.029, 47.231, 137.190, 551.551, 35.646, 24.948, 17.593; all P<0.01), and the difference was statistically significant. Conclusion:The expression of LINC00673 was increased in colon cancer tissues. Inhibition of LINC00673 expression could suppress the EMT by regulating EMT associated genes.
Objective: To investigate the expression and clinical significance of LRFN4 in colorectal cancer. Methods: A total of 210 cases of colorectal cancer tissues and 228 cases of corresponding surgical margin tissues were collected. Immunohistochemistry was employed to evaluate the expression of LRFN4 in colorectal cancer.The correlation between LRFN4 expression and clinicopathological features of colorectal cancer as well as patient outcome were analyzed. Results: The positive rate of LRFN4 in colorectal cancer and in non-cancer was 55.24%(116/210), and 37.28% (85/228) , respectively.The expression of LRFN4 in colorectal cancer tissues was higher than that in non-cancer tissues(χ(2)=14.196, P<0.001). High expression of LRFN4 was significantly correlated with tumor location(χ(2)=4.133,P=0.042), T staging(χ(2)=6.494,P=0.039), N staging(χ(2)=11.715,P=0.008), TNM staging(χ(2)=13.398,P=0.004), CEA (χ(2)=6.017, P=0.049), but without gender, age, degree of differentiation, M staging(P>0.05).The Kaplan-Meier survival curves indicated that high LRFN4 expression was associated with good survival (P<0.05). In addition, Cox proportional hazards model showed that the high expression of LRFN4(HR=0.585, P=0.018)was an independent risk factor for prognosis in patients with colorectal cancer. Conclusions: The expression of LRFN4 is up-regulated in colorectal cancer, which is significantly correlated with the clinicopathological features and prognosis. High expression of LRFN4 reduced the risk of death in patients with colorectal cancer.
目的 对比乳晕皮下与肿瘤周围注射造影剂定位乳腺癌前哨淋巴结(SLN)的效果.方法 回顾性选择2015年6月至2017年6月上海市电力医院普外科收治的乳腺癌患者共98例,分别采用乳晕皮下与肿瘤周围注射造影剂定位乳腺癌SLN,比较两种方法定位SLN的敏感度、特异性和准确度.结果 在98例患者中,亚甲蓝染色共检出SLN 181个,乳晕皮下注射法共检出SLN 162个,检出率为89.50%;肿瘤周围注射法共检出SLN 158个,检出率为87.29%.两者检出率比较差异无统计学意义(χ2=0.572,P=0.833).经乳晕皮下注射超声造影剂检测SLN的准确度为95.68%(155/162),敏感度为96.67%(145/150),特异性为83.33%(10/12).经肿瘤周围注射超声造影剂检测SLN的准确度为79.75%(126/158),敏感度为82.52%(118/143),特异性为53.33%(8/15).结论 经乳晕皮下注射超声造影剂检测SLN,其准确度、敏感度、特异性均高于经肿瘤周围注射的方式,且其检出率高,值得在临床推广应用.
随着医学技术的发展和生活水平的提高 ,保乳手术在确保患者的病灶被全部切除的同时 ,注意乳房的美观 ,被越来越多的女性乳腺癌患者选择并接受.本研究对我院普外科收治的乳腺癌患者的相关病例资料进行回顾性分析 ,并进行患者信任度的随访调查 ,比较改良根治术与保乳术对乳腺癌患者预后、生活质量、心理状态及信任度影响的差异,为保乳术在我院的推广提供理论基础.
Objective To investigate the related factors that affect the short outcome of abdominal surgery among elderly patients with acute abdomen.Methods Clinical data of 378 patients aged >60 years with acute abdo-men were retrospectively analyzed.The key factors under analysis in this study were the occurrence of major complica-tions,death from any cause within 30 days and related factors after the operation.Results The most common diagno-ses were acute appendicitis (134 cases,35.4%),biliary tract disease (96 cases,25.4%),intestinal obstruction (68 cases,20.0%)and inguinal hernia(42 cases,11.1%).The majority of patients(327cases,86.5%)underwent open surgery.12cases(23.5%)of all 51 cases underwent laparoscopic surgery were converted to open surgery.The 30 day mortality rate and rate of operation -related complications were 9.5% and 22.0%,respectively.Analysis showed that patients'age,low body mass index,open surgery and ASA grade Ⅲ or above may increase mortality(all P <0.05).Conclusion The acute abdomen in elderly patients was with much complications,operation treatment is still the first choice.The patient's older age,low body mass index,open surgery may increase the mortality rate.ASA grade higher may predict a bad prognosis.The operation of elderly patiens had a high morbidity and mortality,as general surgeon,we should pay more attention to acute abdomen in elderly patients.