整形保乳术与常规保乳术治疗早期乳腺癌的效果比较

目的:比较整形保乳术与常规保乳术在早期乳腺癌治疗中的应用效果。方法:将新疆医科大学附属肿瘤医院乳腺外科2016年1月至2017年9月收治的66例早期乳腺癌患者纳入本次研究，按照随机双盲法将其分为两组，将采取整形保乳术治疗的33例患者设为研究组，将常规保乳术治疗的33例患者设为对照组，对比两组患者的乳房美容效果、手术情况、住院时间、肿瘤转移复发情况和并发症的发生率。结果:研究组患者乳房美容优良率（97.0%）明显高于对照组（78.8%），手术时间明显长于对照组，术中出血量明显少于对照组，住院时间明显短于对照组，组间比较P＜0.05；两组患者肿瘤转移和复发比率、并发症发生率均无明显差异，组间比较P＞0.05。结论:整形保乳术与常规保乳术在治疗早期乳腺癌中均具有较好的疗效，且并发症发生率均较低，但整形保乳术的乳房美容效果更好，手术创伤更小，术后恢复更快，更值得在临床中推广应用。     

Overexpression of CD44 is associated with a poor prognosis in grade II/III gliomas

Journal of Neuro-Oncology - Overexpression of CD44 has been detected in many types of tumor tissues. Moreover, CD44 is recognized as a cancer stem cell marker for many cancers. However, the...     

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.     

Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAF^V600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAF^V600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAF^V600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.     

Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects

Cancer Chemotherapy and Pharmacology - Zanubrutinib (BGB-3111) is a potent Bruton’s tyrosine kinase inhibitor with promising clinical activity in B-cell malignancies. Zanubrutinib was shown...     

CDC42 promotes vascular calcification in chronic kidney disease

Vascular calcification is prevalent in patients with chronic kidney disease (CKD) and a major risk factor of cardiovascular disease. Vascular calcification is now recognised as a biological process similar to bone formation involving osteogenic differentiation of vascular smooth muscle cells (VSMCs). Cell division cycle 42 (CDC42), a Rac1 family member GTPase, is essential for cartilage development during endochondral bone formation. However, whether CDC42 affects osteogenic differentiation of VSMCs and vascular calcification remains unknown. In the present study, we observed a significant increase in the expression of CDC42 both in rat VSMCs and in calcified arteries during vascular calcification. Alizarin red staining and calcium content assay revealed that adenovirus-mediated CDC42 overexpression led to an apparent VSMC calcification in the presence of calcifying medium, accompanied with up-regulation of bone-related molecules including RUNX2 and BMP2. By contrast, inhibition of CDC42 by ML141 significantly blocked calcification of VSMCs in vitro and aortic rings ex vivo. Moreover, ML141 markedly attenuated vascular calcification in rats with CKD. Furthermore, pharmacological inhibition of AKT signal was shown to block CDC42-induced VSMC calcification. These findings demonstrate for the first time that CDC42 contributes to vascular calcification through a mechanism involving AKT signalling; this uncovered a new function of CDC42 in regulating vascular calcification. This may provide a potential therapeutic target for the treatment of vascular calcification in the context of CKD. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

腹腔镜胆囊切除术后右美托咪定滴鼻镇痛的效果观察

目的观察右美托咪定滴鼻用于腹腔镜胆囊切除术后镇痛的有效性和安全性。 方法选择2021年10月至2022年1月于邛崃市医疗中心医院收治并择期行全身麻醉下腹腔镜胆囊切除术的患者64例，其中男性17例，女性47例；年龄18~65岁，平均(44.03±10.97)岁；体重指数(BMI)<35kg/m²；美国麻醉医师协会(ASA)分级Ⅰ或Ⅱ级。采用随机数字表法将患者分为两组，试验组(D组，31例)于术毕清醒拔除喉罩后给予右美托咪定2 μg/kg滴鼻，对照组(C组，33例)于术毕清醒拔除喉罩后给予等容量0.9%等渗盐水滴鼻。记录两组患者一般情况及术中情况；记录术后2、8、12、24 h静息和运动时视觉模拟评分(visual analogue scale，VAS)；记录术后24 h内补救镇痛的例数以及初次补救镇痛的间隔时间；记录术后24 h内恶心、呕吐的发生例数及严重程度；记录24 h内最满意镇痛且最轻呕吐(satisfactory analgesia with minimal emesis，SAME)的达标比例；记录术后24 h内严重心动过缓、呼吸抑制、循环不稳、镇静过度等不良反应的发生情况。 结果与C组比较，D组2、8 h静息和运动VAS评分及12 h运动VAS评分明显降低(P<0.05)，两组术后补救镇痛的次数差异无统计学意义(P>0.05)，但D组初次补救镇痛的间隔时间明显延长(P<0.05)。与C组比较，D组术后恶心呕吐的发生率及严重程度明显降低(P<0.05)。D组SAME达标率明显高于C组(P<0.05)。两组患者术后均未出现严重心动过缓、呼吸抑制(SPO₂低于95%)、循环不稳(需要药物干预)、镇静过度等不良反应。 结论腹腔镜胆囊切除术后右美托咪定2 μg/kg滴鼻能在不辅助其他术后镇痛药的情况下，改善患者术后疼痛及恶心呕吐，延长初次补救镇痛的间隔时间，且无明显不良反应。     

香萱益神方对血管性痴呆模型大鼠神经元凋亡机制研究

目的:探讨香萱益神方治疗血管性痴呆(VD)模型大鼠认知功能作用及其对神经元凋亡机制的研究。方法:两血管阻断法建立VD大鼠模型,给予中药方香萱益神方灌胃治疗6周,分别于造模后、中药喂养6周后进行Morris水迷宫行为学检测,测试大鼠认知行为能力改变,行为学测试结束后,检测VD模型大鼠海马中海马组织脑源性神经营养因子(BDNF)表达水平的变化。结果:香萱益神方治疗6周后,血管性痴呆大鼠模型学习记忆能力得到改善,上调脑内海马组织神经营养因子水平,海马神经元凋亡率下降。结论:香萱益神方是治疗血管性痴呆的有效方剂,可以有效改善VD大鼠模型认知行为功能的障碍情况,起到减少海马神经元细胞凋亡,诱导海马神经元细胞修复的作用。香萱益神方可能是通过激活BDNF相关通路,起到保护海马神经元的作用。