A study of gene variation in All-RAS wild-type metastatic colorectal cancer and its correlation with cetuximab

BackgroundThis study sought to explore the biological significance of genetic variation in RAS wild-type metastatic colorectal cancer (mCRC) in the real world, the difference in the efficacy of cetuximab in the treatment of mCRC with different genetic variants and identify clinical features and new predictors of efficacy.MethodsA retrospective analysis of the data of 60 patients with stage IV mCRC who received cetuximab at The First and Second Affiliated Hospital of Soochow University from 2016 to 2020 was conducted. The patients were divided into the following 3 groups according to the genetic test results: (I) group A (the all-RAS wild-type group); (II) group B (the all-RAS wild-type group with the tumor suppressor gene mutation); and (III) group C (the all-RAS wild-type group with the oncogenic driver gene mutation). A subgroup analysis was conducted to examine left CRC and local intervention, and the progression-free survival (PFS) and overall survival (OS) of the patients were observed.ResultsThe all-RAS wild-type mCRC patients were divided into group A (n=10), group B (including the TP53, APC, PTEN, BRCA2, and SMAD4 variants) (n=42), and group C (including the ERBB2, BRAF, PIK3CA, and RET variants) (n=8). The median PFS of groups A, B, and C were 15.0, 12.0, and 3.0 months, respectively (P=0.007). Fitting sex as a stratified variable to the Cox survival analysis model showed that only the PFS of groups B and C differed significantly (P=0.011). In the left-sided mCRC patients, the median PFS of groups A, B, C were 3.0, 13.0, and 3.0 months, respectively (P=0.009). Among the patients in group B, the median PFS of the metastatic local intervention subgroup was 14.0 months, and the non-local intervention subgroup was 12.0 months (P=0.55). Only the type of combined gene mutation was an independent factor affecting PFS.ConclusionsThe PFS and OS of mCRC patients with all-RAS wild-type and no combined mutations treated with cetuximab were not better than those of patients with combined mutations. Compared to mCRC patients with all-RAS wild-type and oncogenic driver gene mutations, cetuximab significantly prolonged the PFS of all-RAS wild-type patients with the tumor suppressor gene mutations.     

Racial disparities and standard treatment in locally advanced rectal cancer: a National Cancer Database study

BackgroundMortality rates in colorectal cancer (CRC) continue to be higher in Black compared to White patients. While standard treatment modalities for locally advanced rectal cancer have been shown to improve outcomes, there are limited studies assessing the receipt of standard treatment in rectal cancer based on race. Therefore, we sought to evaluate the use of standard treatment across racial groups in locally advanced rectal cancer and its effect on survival.MethodsThe National Cancer Database (NCDB) was queried for patients ≥18 years old with clinical and pathologic stage II–III rectal adenocarcinoma who received treatment from 2004 to 2014. Standard treatment was defined as complete surgical excision with either neoadjuvant or adjuvant concurrent chemoradiation. Multivariable logistic regressions were used to identify racial differences in receiving standard treatment. Cox proportional hazards were used to estimate the effects of standard vs. nonstandard treatment on survival differences based on race.ResultsA total of 70,677 patients with stage II (n=35,079) or stage III (n=35,598) rectal adenocarcinoma met the inclusion criteria. On multivariate analysis, Black [odds ratio (OR): 0.75; 95% confidence interval (CI): 0.71–0.79; P<0.001] and Hispanic White (OR: 0.86; 95% CI: 0.80–0.92; P>0.001) patients were less likely to receive standard treatment compared to non-Hispanic White patients. On multivariable Cox regression, nonstandard treatment was significantly associated with worse survival [hazard ratio (HR): 1.69; 95% CI: 1.65–1.73; P<0.001] compared to standard treatment. Even after adjusting for patient, demographic, and facility characteristics, Black patients had higher mortality rates compared to White patients in the whole population (HR: 1.15; 95% CI: 1.09–1.20; P<0.0001). This survival difference between Black and non-Hispanic White patients persisted in both the standard (HR: 1.10; 95% CI: 1.03–1.19; P=0.008) and nonstandard (HR: 1.17; 95% CI: 1.10–1.25; P<0.0001) treatment subgroups. Decreased survival outcomes in Black patients were more pronounced for those who underwent nonstandard treatment, particularly when treating stage III disease (HR: 1.30; 95% CI: 1.19–1.42; P<0.0001).ConclusionsNonstandard treatment in stage II and III rectal cancer is associated with worse survival compared to standard treatment regimens. Black patients are more likely to receive nonstandard treatment and have worse survival outcomes compared to White patients.     

The recent development of nanozymes for targeting antibacterial,anticancer and antioxidant applications

Nowadays, nanozymes have not only been used as biosensors in the detection field, but also their application prospects in disease treatment have been explored. Numerous nanomaterials have similar catalytic activities such as peroxidase, oxidase, catalase and superoxide dismutase, and they can be used for antibacterial, anticancer and antioxidant therapy. Although there have been many studies on the application of nanozymes in the therapeutic field, the current nanozyme-based systems often lack targeting and ignore the harm to the surrounding normal tissues. Although promising, the biosafety of nanomaterials has always been the concern of researchers. To improve the treatment effect and reduce toxic and side effects, precision treatment has become the key. At present, a few studies have modified targeted molecules on nanozymes to achieve precise targeting through specific interaction with surface overexpression factors of bacteria or cells. Combined with the catalysis of nanozymes, the targeted treatment of diseases can be achieved. This review summarizes the current research of nanozyme systems in targeted antibacterial, anticancer and antioxidant applications. At the same time, the challenges and development prospects of nanozyme-based targeted therapy system are summarized. It is expected that this work will provide new ideas and new directions for the precise treatment of nanozymes.

The recent development of nanozymes for targeting antibacterial, anticancer and antioxidant applications are summarized.     

NLRP3基因多态性与中国北方东部汉族人群帕金森病相关性研究

目的探讨Nod样受体家族蛋白3 (Nod-like receptor protein 3,NLRP3)rs4612666及rs7525979位点多态性与中国北方东部汉族人群帕金森病(Parkinson disease,PD)发病风险的相关性。方法采用病例对照研究,共招募400例PD患者(PD组)及400例健康对照者(对照组),应用聚合酶链反应-限制性片段长度多态性方法鉴定NLRP3基因SNPs位点rs4612666和rs7525979。结果 PD组rs4612666等位基因与对照组具有统计学差异,C等位基因频率低于对照组,降低发病风险(OR=0.794,95%CI:0.653～0.967,P=0.021),隐性遗传模型CC/TT+CT分布在PD组与对照组之间差异具有统计学意义(OR=0.667,95%CI:0.481～0.925,P=0.015)。亚组分析中,与对照组比较,女性PD组与早发型PD组等位基因分布差异具有统计学意义(P=0.003,P=0.018)。rs7525979位点的基因型分布和等位基因频率在PD组与对照组比较均无统计学差异(P>0.05)。结论在中国北方东部汉...     

产前超声在胎儿先天性膈疝诊断中的应用

目的探讨产前超声检查在胎儿先天性膈疝诊断中的应用价值。方法回顾性分析20例CDH胎儿的超声资料,并与引产后尸体解剖结果及手术结果进行对照分析。结果20例CDH中,产前超声检出19例,平均检出时间26.1周。左侧膈疝15例,右侧膈疝4例。8例合并其他畸形。其中合并消化系统畸形3例,生殖泌尿系统畸形2例,心血管系统畸形2例,骨骼系统畸形1例。漏诊1例。结论产前超声检查对CDH的筛查有重要的临床价值。     

口服Cocktail A乳酸菌制剂对人肠道乳酸菌群影响的研究

目的评价口服Cocktail A乳酸菌制剂后人肠道乳酸菌群的变化。方法用需氧和厌氧定量培养方法分离并鉴定烧伤病房中30例腹泻患者给予Cocktail A乳酸菌制剂治疗前后肠道中的细菌,并以正常健康体检者的粪便培养鉴定结果作为对照。同时对未鉴定出的细菌用16S rRNA基因进行鉴定。结果腹泻患者肠道中的菌群与健康体检者肠道中的菌群相比,乳酸菌的数量和种类少,而口服乳酸菌制剂治疗后肠道中的植物乳杆菌、明串珠球菌、戊糖片球菌、副酪蛋白乳杆菌大量增加。结论口服Cocktail A乳酸菌制剂能调节肠道的菌群失调。     

骨髓间充质干细胞不同移植方法治疗脊髓损伤的实验研究

为探讨骨髓基质干细胞(MSCs)不同的移植方法对脊髓损伤修复的影响,我们采用静脉移植、蛛网膜下腔移植或腹腔移植荧光标记MSCs的方法检测MSCs在损伤处的分布迁移情况及运动功能恢复情况。结果显示:各种移植方法在损伤脊髓节段上、下均可检测到荧光标记的MSCs,不同移植方法在损伤脊髓内荧光标记的MSCs数量有所不同。损伤脊髓节段和非损伤脊髓节段内的细胞数量和密度也有明显差异(P<0.05)。BBB评分显示:术后第2d各组平均未超过1分者,移植后的1周内无明显差异(P>0.05);3周后,各组间差异也不大(P>0.05),但各移植组同对照组相比有明显差异(P<0.05)。以上结果提示:通过各种移植方法MSCs均可迁移到损伤脊髓节段,并在该部位存活、聚集和向损伤部位迁移,说明MSCs不同的移植方法对于治疗脊髓损伤均有一定的作用。     

青少年鼻咽癌治疗现状

鼻咽癌(NPC)是一种起源于鼻咽部上皮细胞的恶性肿瘤,是青少年人群头颈部最常见的恶性肿瘤之一。青少年鼻咽癌的治疗通常参照成人治疗指南,但是青少年鼻咽癌有其自身的临床特点。对于处于发育阶段的青少年患者来说,治疗的晚期不良反应也不可忽视。寻找适合青少年的治疗方案具有重要意义。本文对青少年鼻咽癌的流行病学、临床特点、治疗现状...     

The Potential Roles of Dietary Anthocyanins in Inhibiting Vascular Endothelial Cell Senescence and Preventing Cardiovascular Diseases

Cardiovascular disease (CVD) is a group of diseases affecting the heart and blood vessels and is the leading cause of morbidity and mortality worldwide. Increasingly more evidence has shown that the senescence of vascular endothelial cells is the key to endothelial dysfunction and cardiovascular diseases. Anthocyanin is a type of water-soluble polyphenol pigment and secondary metabolite of plant-based food widely existing in fruits and vegetables. The gut microbiome is involved in the metabolism of anthocyanins and mediates the biological activities of anthocyanins and their metabolites, while anthocyanins also regulate the growth of specific bacteria in the microbiota and promote the proliferation of healthy anaerobic flora. Accumulating studies have shown that anthocyanins have antioxidant, anti-inflammatory, and anti-aging effects. Many animal and in vitro experiments have also proven that anthocyanins have protective effects on cardiovascular-disease-related dysfunction. However, the molecular mechanism of anthocyanin in eliminating aging endothelial cells and preventing cardiovascular diseases is very complex and is not fully understood. In this systematic review, we summarize the metabolism and activities of anthocyanins, as well as their effects on scavenging senescent cells and cardioprotection.