Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.     

Short- and Long-Term Outcome after Emergent Cardiac Surgery during Transcatheter Aortic Valve Implantation

Objective: Our study aimed to evaluate short- and long-term outcomes of patients who required emergent conversion from transcatheter aortic valve implantation (TAVI) to open surgery. Besides, the reasons and procedural settings of emergent cardiac surgery (ECS) were also reported.Methods: We retrospectively reviewed the patients who underwent TAVI in our institution between 2012 and 2019 and collected the clinical data of cases who converted from TAVI to bail-out surgery. Telephone and outpatient follow-ups were performed.Results: Of 516 TAVI patients, 20 required ECS, and the bail-out surgery occurred less frequently with the increase in TAVI volume. The most common reason for conversion was left ventricular perforation (7/20, 35.0%). Thirty-day mortality was 35.0% in ECS patients. Kaplan–Meier survival curves showed that the cumulative survival rate was 65.0% at 1 year, 50.1% at 5 years in all ECS patients, and 77.1% at 5 years in patients who survived over 30 days after conversion.Conclusion: Although the bail-out operation was performed immediately after TAVI abortion, ECS still associated with high 30-day mortality. The long-term survival benefit was seen in patients surviving from bail-out surgery. An experienced TAVI team is of crucial importance in avoiding ECS-related life-threatening complications and providing effective salvage surgery.     

Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.MethodsA total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27–78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.ResultsA total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0–28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III–IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III–IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).ConclusionsThe most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III–IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I–II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.     

MAKO机器人辅助单髁置换手术的护理配合

机器人技术在微创领域的作用越来越突出,而高质量护理工作的配合可以保障机器人手术的安全、有效进行,且有利于患者术后稳定情绪和更好的恢复.为提升护理工作者对MAKO机器人辅助单髁置换手术的全面认识,优化护理工作的模式和流程,提高手术效率并改善患者术后恢复效果,本文在现有的相关文献资料基础上,结合北京大学人民医院11例行机器人单髁置换手术的实际工作体会,用理论联系实际,对术中的护理配合工作进行系统地分析.本团队认为,在机器人辅助单髁置换手术中,护理工作应在传统经验积累的基础上,进一步提高护理配合熟练程度.随着科技的进步,MAKO机器人辅助单髁置换手术的医护模式也将进一步的智能化和数字化.     

车祸致颅脑损伤患者家属心理健康状况与社会支持相关性研究

目的 了解车祸致颅脑损伤患者家属的心理健康状况和社会支持状况,探讨其相关性。方法 采用自编一般资料调查表、症状自评量表（SCL - 90）和社会支持量表（SSRS）,对225名到精神专科医院就诊的车祸致颅脑损伤患者家属进行问卷调查。结果 车祸致颅脑损伤患家属的SCL - 90总分为（178.45±82.56）分, SCL - 90总分、阳性项目数和9个因子分均显著高于肿瘤患者家属和全国常模(P＜0.05)。社会支持总分为（38.52±8.23）分,社会支持水平与家属的心理健康状况呈显著的负相关（r = - 0.416, P＜0.05）。多元线性回归分析显示,社会支持总分可以负向预测家属的心理健康状况（β = - 0.399,P＜0.05）。结论 车祸致颅脑损伤患者家属的心理问题发生率较高,应从个人、家庭和社会层面为家属提供社会支持资源。     

OK-432增强脐血树突状细胞瘤苗抗胃癌作用的实验研究

目的： 用脐血浆代替胎牛血清，观察OK-432对脐血来源的树突状细胞（DCs）功能的影响，探讨制备高效抗肿瘤DCs疫苗的优化方案。方法: 分离脐血单个核细胞并在含10%同源脐血浆、GM-CSF和IL-4的培养体系中诱导培养，部分加入肿瘤冻融抗原和/或OK-432冲击,MTT法检测DCs体外刺激同种混合淋巴细胞增殖的免疫活性，LDH法检测DCs诱导的CTL对不同靶细胞的细胞毒作用。结果: 收集第9 d的各组DCs，肿瘤冻融抗原冲击后的DCs呈成熟形态，能呈递胃癌相关抗原给淋巴细胞刺激其增殖并诱导对胃癌细胞株特异的CTL毒性。OK-432联合肿瘤冻融抗原冲击能增强其抗原呈递功能，诱导更强的混合淋巴细胞增殖反应及针对胃癌细胞株的强烈CTL杀伤效应。结论: 该DCs培养方案具有培养时间短、细胞因子消耗少、试剂简单等优点,可用于制备DCs肿瘤疫苗,有临床应用价值。     

中医药多途径介入低预后再次IVF-ET拮抗剂方案患者卵巢功能、中医证候及自孕的临床疗效评估

目的 分析中医药多途径介入对体外受精-胚胎移植（IVF-ET）失败后拟再次接受IVF-ET拮抗剂方案低预后（肾阴虚肝郁血瘀证）患者卵巢功能、中医证候及自然受孕情况的影响。方法 选取2020年8月至2023年2月在四川大学华西第二医院、成都中医药大学附属医院就诊拟再次接受IVF-ET拮抗剂方案助孕且符合纳入标准的肾阴虚肝郁血瘀证低预后患者128例,按随机对照表分为观察组和对照组,每组各有患者64例。对照组采用口服脱氢表雄酮（DHEA）治疗,观察组采用多途径中医药（口服中药汤剂+耳穴贴压+补肾活血方导法）治疗。经过3个月经周期的治疗后,收集两组患者的卵巢功能评估相关指标,中医证候评分和自然受孕情况。结果 与本组治疗前比较,观察组患者基础卵泡刺激素（bFSH）、基础卵泡刺激素/基础黄体生成激素（bFSH/bLH）值、基础雌二醇（bE₂）、窦卵泡数（AFC）、获卵数、正常受精数、优胚数、中医证候评分在治疗后均有明显改善（P<0.05,P<0.01）,对照组患者bFSH/bLH、中医证候评分均较治疗前升高（P<0.05）,而bFSH、bE₂、AFC值、获卵数、正常受精数、优胚数差异无统计学意义。治疗后观察组患者bFSH、bFSH/bLH、bE₂、AFC、正常受精数、优胚数、中医证候评分改善情况均优于对照组（P<0.05,P<0.01）,而获卵数差异无统计学意义。治疗后,观察组自然受孕3人,而对照组无自然受孕者。结论 对于IVF-ET失败后,拟再次接受IVF-ET拮抗剂方案的肾阴虚肝郁血瘀证低预后患者,通过多途径的中医药干预,可以降低bFSH、bFSH/bLH值、改善bE₂水平,增加AFC、获卵数、正常受精数和优胚数,改善卵巢功能、月经状况和中医证候,提高生活质量,使部分患者在再次进周前自然受孕,改善妊娠结局。     

不同机制大动脉粥样硬化型脑卒中基线特征和血管内治疗后结局比较

目的 本研究旨在比较颅内大血管伴/不伴同侧颈内动脉闭塞的大动脉粥样硬化型脑卒中患者基线特征以及行血管内治疗后结局的差异。方法 对DIRECT-MT亚组进行回顾性分析,以比较前循环大动脉粥样硬化（large-artery atherosclerosis,LAA）型卒中串联闭塞和颅内闭塞接受血管内治疗（endovascular treatment,EVT）的患者的基线特征和预后,分析不同机制学特征（动脉粥样硬化或动脉-动脉栓塞）对临床结局的影响。结果 LAA型卒中患者共108例,其中串联闭塞63例,颅内闭塞45例。颅内闭塞组患者高血压史率高于串联闭塞组（77.8% vs. 52.4%, P=0.007）。颅内闭塞组闭塞部位最常见于大脑中动脉M1段（88.6%）,而串联闭塞组颅内闭塞主要位于颈内动脉颅内段（49.2%）和大脑中动脉M1段（49.2%）（P＜0.001）。两组患者在年龄、性别、术前抗栓、他汀类药物的使用,卒中、房颤、吸烟史,基线mRS、NIHSS评分,是否静脉溶栓,侧枝循环,以及救治流程时间差异均无统计学意义（P均＞0.05）。90天mRS 0-2分的患者比例两组差异无统计学意义（53.3% vs. 41.9%, P=0.243）。颅内闭塞组术后成功再灌注率高于串联闭塞组（93.3% vs. 77.4%, P=0.026）,但术后24-72小时血管再通的比例前组低于后组（57.1% vs. 77.2%, P=0.034）。最终梗死体积,颅内闭塞组小于串联闭塞组（20.1 vs. 34.5, P=0.025）。术后NIHSS评分,90天EQ-5D-5L评分和BI指数等其他次要结局,两组间差异无统计学意义（P均＞0.05）。两组在90天内的死亡率,发生的无症状性和症状性颅内出血率,5-7天时在另外的血管区域新发脑梗死,以及新流域栓塞的患者百分比相似,差异无统计学意义（P均＞0.05）。结论 动脉粥样硬化导致的串联闭塞相较于孤立颅内闭塞,末次造影成功再灌注率较低,梗死体积更大,但术后24-72小时再通率更高,且神经功能良好预后率以及不良事件发生率均与颅内闭塞相仿。     

Homer 1b/c通过内质网功能调节由谷氨酸诱发的HT22细胞自噬

目的　研究Homer1b/c蛋白在谷氨酸诱发的细胞自噬中的作用及机制。方法　选用小鼠海马细胞系HT22细胞,通过500 ?mol/L谷氨酸处理建立细胞损伤模型。用siRNA慢病毒转染方式下调Homer1b/c表达和10 ?mol/LBAPTA-AM（1,2-双(2-氨基苯氧基)乙烷-N,N,N`,N`-四乙酸四乙酸甲酯,钙离子螯合剂）、10 mmol/L4-PBA（4-苯基丁酸,内质网应激抑制剂）分别抑制细胞内钙离子释放和内质网应激后,使用蛋白质印迹法检测Homer1b/c,自噬蛋白Beclin-1、微管相关蛋白轻链3（LC3）,以及内质网应激标志蛋白CHOP（人内质网应激相关蛋白）、GRP-78(葡萄糖调节蛋白78)的表达水平。每组实验均进行3次,采用独立样本t检验和单因素方差分析进行统计学分析。结果　谷氨酸处理HT22细胞12 h后,Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值均升高（P<0.05）,下调Homer1b/c表达可降低Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值的升高程度（P<0.05）。抑制细胞内钙离子释放和抑制内质网应激均能降低Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值的升高程度（P<0.05）。然而在下调Homer1b/c表达后,抑制细胞内钙离子释放和抑制内质网应激未能进一步降低Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值的升高程度（P<0.05）。结论　Homer1b/c能够调节谷氨酸诱导的自噬,其调节作用可能与内质网功能有关。     

Apolipoprotein E gene polymorphism and its association with human longevity in the Uygur nationality in Xinjiang

Objective To study the relationship between apoE alleles and life-span.Methods Apolipoprotein E genotypes were determined in 164 unrelated Uygurs including 35 persons aged 90 years or older, 71 men aged 20-35 and 54 men with myocardial in farction by using polymerase chain reaction-restriction fragment length polymor phism.Apolipoprotein E gene polymorphism was analyzed among three groups. Results There was statistically significant difference in the ε4 allele frequencies amo ng three groups.The ε4 allele frequency in olds was the lowest (0.057), whil e in patients suffering from myocardial infarction (MI) was the highest (0.213) .In MI patients the average age of first attack in ε4 allele carriers was sig nificantly younger than that of non-carries, 51.3 and 58.3 years, respectivel y (P&lt;0.05).Conclusion ApoE genotype may have some impact on human longevity.