Comparison of the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma: a retrospective cohort study

BackgroundThere is lack of studies on sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma (HCC). This study was to explore the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib failure in HCC patients.MethodsThis study was a retrospective, real-world study that included 50 HCC patients who received sequential regrafinib after sorafenib and lenvatinib failure. The safety and prognosis of two groups were compared.ResultsThe incidence of all grade and III/IV adverse events were 68% and 24%. According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and modified (m) RECIST standards, the objective response rates (ORRs) after receiving regorafenib were 14.0% and 22.0%, respectively. The disease control rates (DCRs) were 62.0% and 60.0%, respectively. Based on different first-line targeted drugs, 50 patients were divided into sorafenib (n=22) and lenvatinib group (n=28). There was no differences between two groups except age and bilirubin. And there was no differences in other treatments before or after regorafenib. The baseline between two groups was basically same and had good comparability. There was no difference in incidence of all grade and III/IV adverse events, ORR and DCR between two groups (P>0.05). On long-term prognosis, total overall survival (TOS) in sorafenib and lenvatinib group were 23.0 (95% CI: 15.1–30.9) vs. 29.7 (95% CI: 21.4–38.1) months. The difference was statistically significant (P=0.041). Besides, regorafenib overall survival (ROS) in sorafenib and lenvatinib group were 11.7 (95% CI: 7.1–16.3) vs. 15.9 (95% CI: 8.3–23.5) months. The difference was statistically significant ( P=0.045). The regorafenib progression-free survival (RPFS) was 5.6 (95% CI: 1.9–9.2) vs. 8.0 (95% CI: 5.1–10.9) months in sorafenib and lenvatinib group, respectively, and difference was not statistically significant (P=0.380).ConclusionsRegorafenib is an effective drug for second-line treatment of HCC, with fewer severe adverse events, ORR and DCR was 14–22% and 62–60%, respectively. Both TOS and ROS in lenvatinib group were better than those in sorafenib group. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after disease progresses.     

Corosolic acid analogue,a natural triterpenoid saponin,induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro

Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine.

Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines.

Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40?μg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4′-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays.

Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24?h, the IC₅₀ values were 34.6, 30.8 and 30.5?μg/mL, respectively. TEO (40?μg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio.

Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway.     

上海市社区中医药健康教育达标建设现状分析

为全面反映上海市社区中医药健康教育的开展情况,了解存在问题,给中医药健康教育的进一步研究提供借鉴。2009年9月,在原上海市卫生局的支持下,在上海市中医药社区卫生服务研究中心的协助下,上海杏灵科技药业股份有限公司申报＂上海市社区中医药健康教育现状与对策研究＂课题,并获得＂上海市卫生局中医药科研基金＂正式批准立项,承担调查研究工作。     

辽宁阜新农村地区蒙汉两族高血压发病率及其预测因素的比较

目的比较分析阜新农村地区蒙汉两族高血压发病率及其预测因素。方法前瞻性人群随访研究。结果随访期间24.6%的汉族和34.5%的蒙族人群发展为临床高血压,但是高血压的控制率非常低(汉族1.34%,蒙族1.54%)。蒙族人群高血压年发病率为14.16/100人年[95%CI:(13.52～14.82)/100人年],汉族人群高血压年发病率为10.74/100人年[95%CI:(10.45～11.03)/100人年](P<0.05)。与汉族相比,蒙古族发展为高血压的危险比(HR)为1.131(95%CI:1.068～1.198)。女性、基线年龄、高血压前期、超重和肥胖及高血压家族史与蒙汉两族高血压发病均相关,然而饮酒只和蒙族高血压发病相关(HR:1.128;95%CI:1.045～1.219)。与有高血压家族史的汉族人群(增加12%)相比,有高血压家族史的蒙族人群发展为高血压的风险大幅提高(增加60%)。结论蒙族人群高血压发病率高于汉族人群;饮酒和高血压家族史可能是导致差异的主要原因。     

Neural representation of phonological information during Chinese character reading

Previous studies have revealed that phonological processing of Chinese characters elicited activation in the left prefrontal cortex, bilateral parietal cortex, and occipitotemporal regions. However, it is controversial what role the left middle frontal gyrus plays in Chinese character reading, and whether the core regions (e.g., the left superior temporal gyrus and supramarginal gyrus) for phonological processing of alphabetic languages are also involved in Chinese character reading. To address these questions, the present study used both univariate and multivariate analysis (i.e., representational similarity analysis, RSA) to explore neural representations of phonological information during Chinese character reading. Participants were scanned while performing a reading aloud task. Univariate activation analysis revealed a widely distributed network for word reading, including the bilateral inferior frontal gyrus, middle frontal gyrus, lateral temporal cortex, and occipitotemporal cortex. More importantly, RSA showed that the left prefrontal (i.e., the left middle frontal gyrus and left inferior frontal gyrus) and bilateral occipitotemporal areas (i.e., the left inferior and middle temporal gyrus and bilateral fusiform gyrus) represented phonological information of Chinese characters. These results confirmed the importance of the left middle frontal gyrus and regions in ventral pathway in representing phonological information of Chinese characters.     

慢性鼻-鼻窦炎筛窦骨质病理形态学改变及其相关因素分析

目的:研究慢性鼻-鼻窦炎(CRS)筛窦骨质病理形态学改变的相关因素。方法:CRS患者180例,其中Ⅰ、Ⅱ和Ⅲ型各60例,鼻内镜手术中取带有筛窦黏膜的筛骨标本送病理苏木精-伊红染色,对其病理形态学改变严重程度进行分级。统计不同临床分型其病理分级的例数及所占比率。分析筛窦骨质病理改变严重程度与筛窦黏膜病理改变程度、筛窦CT分型、病程长短及是否有手术史的关系。结果:所有患者筛窦骨质发生不同程度的病理形态学改变。病理分级:Ⅰ级5例(2.78%),Ⅱ级38例(21.11%),Ⅲ级71例(39.44%),Ⅳ级66例(36.67%)。Ⅰ、Ⅱ和Ⅲ型的筛骨病理分级结果:Ⅰ型,Ⅰ级5例(8.33%),Ⅱ级33例(55.00%),Ⅲ级15例(25.00%),Ⅳ级7例(11.67%);Ⅱ型,Ⅱ级5例(8.33%),Ⅲ级37例(61.67%),Ⅳ级18例(30.00%);Ⅲ型,Ⅲ级19例(31.67%),Ⅳ级41例(68.33%)。180例CRS患者不同临床分型、筛窦黏膜病理改变严重程度、不同筛窦CT分型、病程长短及是否有手术史与筛窦骨质病理分级均差异有统计学意义(均P<0.01)。结论:CRS筛窦骨质发生不同程度的病理形态学改变,其...     

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma: clinical outcomes and patterns of failure

The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.     

声带息肉患者术后声休方案探讨

目的探讨声带息肉患者喉显微手术后声休方案。方法85例声带息肉患者随机分为两组,A组48例,B组37例,均在显微支撑喉镜下行声带息肉切除术,A组术后严格声休1周,B组术后严格声休2周,其余治疗相同。两组均于手术前和手术后1、2、3、4周行嗓音基频微扰（jitter）、振幅微扰（shimmer）、噪谐比（NHR）检测和纤维喉镜检查,比较两组术后发声功能及声带手术创面恢复情况。结果术后1周时A、B两组jitter、shimmer、NHR值均与术前比较差异无统计学意义（P＞0．05）;术后2周时,A组仅jitter较术前降低（P＜0．05）,shimmer、NHR值仍与术前无差异,而B组jitter、shimmer、NHR值均较术前降低（P＜0．05）,且B组shimmer值较 A组低（P＜0．05）;术后3周时B组jitter、shimmer、NHR值均低于A组;术后4周时两组jitter、shimmer、NHR值均恢复至正常水平。纤维喉镜检查显示术后1周时两组患者术侧声带均有不同程度充血水肿,部分患者创面可见少许伪膜;术后2周时声带充血水肿逐渐消退,伪膜脱落;至术后4周时,两组患者术侧声带外观完全恢复正常。结论声带息肉患者术后2周应严格声休,术后3～4周应相对声休,以利于声带创面的愈合及发声功能的恢复。     

Feasibility of sentinel lymph node biopsy omission after integration of 18F-FDG dedicated lymph node PET in early breast cancer:a prospective phase Ⅱ trial

Objective:Sentinel lymph node biopsy(SLNB) is currently the standard of care in clinically node negative(cN0) breast cancer.The present study aimed to evaluate the negative predictive value(NPV) of ¹⁸F-FDG dedicated lymph node positron emission tomography(LymphPET) in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients ...