Genetic diagnosis in a Chinese Hailey–Hailey disease pedigree with novel ATP2C1 gene mutation

Hailey–Hailey disease (HHD) is an autosomal dominant skin disorder characterized by recurrent eruption of vesicles and bullae at the sites of friction and in the intertriginous areas. Mutations in the ATP2C1 gene encoding the human secretory pathway calcium ATPase 1 (hSPCA1) have been identified as the causative mutations in HHD. In this study, we used direct sequencing and restriction endonuclease digestion to analyze mutations of the ATP2C1 gene in a Chinese three-generation pedigree. A heterozygous T-to-C transition at nucleotide 1004 in exon 12 of ATP2C1 gene was detected. After summarizing the reported cases with ATP2C1 mutation, we concluded that the T1004C transition resulted in a novel missense mutation of leucine condon (CTG) to proline (CCG) at amino acid residue 335(L335P) in hSPCA1. Here, a genetic diagnosis was made for the proband’s daughter before the clinical presentation. The study realized the molecular diagnosis in the HHD pedigree. Our findings should be useful for genetic counseling and prenatal diagnosis for the affected family and in demonstrating the critical role of the ATP2C1 gene in the pathogenesis of HHD further.     

Effect of Trastuzumab on Health-Related Quality of Life in Patients With HER2-Positive Metastatic Breast Cancer: Data From Three Clinical Trials

BackgroundTrastuzumab (Herceptin®; Genentech, Inc.; South San Francisco, CA) provides clinical benefit when combined with chemotherapy or as monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Given the demonstrated improvement in standard outcomes, it is important to assess this therapy—s effect on patients' health-related quality of life (HRQOL).Patients and MethodsThe QLQ-C30 and BR-23 questionnaires were used to assess global HRQOL; physical, social, and role functioning; and fatigue as secondary endpoints in trials of trastuzumab monotherapy (H0649g and H0650g) or in combination with chemotherapy (H0648g). Patients completed assessments at baseline, week 8 (H0648g only), and at 12-week intervals until disease progression.ResultsIn H0648g (n = 400), more patients exhibited improved global QOL in the chemotherapy-plus-trastuzumab versus chemotherapy arms (51% vs. 36%; P < .05). In the chemotherapy-plus-trastuzumab arm, fatigue was significantly improved at week 32 (chemotherapy completed at week 20) compared with baseline in both study arms (P < .05); more patients in the chemotherapy-plus-trastuzumab arm also showed improved physical and role functioning. Subscale scores in H0649g (n = 154) and H0650g (n = 74) were similar at all time points. In H0649g, clinical responders showed meaningful improvements (≥ 10 points) in all 5 subscales by week 12 through week 36. Nonresponders had meaningful decreases in all subscale scores. In H0650g, clinical responders exhibited meaningful increases in social and role functioning and global QOL by week 12; nonresponder scores worsened for all subscales.ConclusionTrastuzumab has a beneficial effect on HRQOL in patients with HER2-positive MBC, particularly those with responsive disease.     

妊娠相关性宫颈癌19例临床分析

目的:分析妊娠相关性宫颈癌的临床病理资料及影响预后的因素,探讨妊娠相关性宫颈癌的治疗方案.方法:收集2000年1月至2006年12月收治的19例妊娠相关性宫颈癌患者的临床资料进行回顾性分析,用Kaplan-Meier法、Log-rank检验、COX回归模型进行统计学分析.结果:19例妊娠相关性宫颈癌患者中位生存时间为34.33个月,5年生存率为46.62％.单因素分析显示肿瘤大小(P =0.034)、FIGO临床分期(P=0.046)、组织学分级(P =0.047)、终止妊娠的方式(P =0.033)、根治性手术(P=0.020)、淋巴结转移(P =0.016)与预后有关.多因素分析显示是否行根治性手术(P=0.021)、淋巴结转移(P =0.012)是影响预后的独立因素.结论:对于妊娠相关性宫颈癌,是否行根治性手术、淋巴结转移是影响预后的独立因素,行宫颈癌根治术手术可以延长生存时间.     

Palbociclib plus letrozole as first-line treatment for ER-positive and HER2-negative advanced breast cancer in Chinese women: a phase 1 study

BackgroundPalbociclib, a cyclin-dependent kinase 4 and 6 inhibitor, is approved in many countries for the treatment of ER-positive and HER2-negative advanced breast cancer in combination with endocrine therapy. We aimed to evaluate the pharmacokinetics, safety, and efficacy of palbociclib combined with letrozole as first-line treatment for ER-positive and HER2-negative advanced breast cancer.MethodsThis is a phase 1, open-label, single-arm study in Chinese women with ER-positive and HER2-negative advanced breast cancer. From cycle 1 day 1, patients received letrozole 2·5 mg orally once daily continuously plus palbociclib 125 mg orally once daily for 3 weeks followed by 1 week off treatment. Blood samples for pharmacokinetic evaluation of palbociclib were collected up to 120 h after a single dose of palbociclib in a lead-in phase and after palbociclib dose on cycle 1 day 21 for multiple dose pharmacokinetic evaluation. Predose blood samples for pharmacokinetic evaluation of palbociclib and letrozole were collected on days 19–21 of cycle 1 and cycle 2 day 1 (letrozole only). Disease assessments were done every 12 weeks from cycle 1 day 1. Safety was assessed per Common Terminology Criteria for Adverse Events, version 4.0. This study is registered with ClinicalTrials, number NCT02499146, and is ongoing but not recruiting.FindingsAs of March 16, 2016, the cutoff date, the study completed enrolment with 26 patients. All patients completed single dose pharmacokinetic evaluation and 13 completed multiple dose pharmacokinetic evaluation. After multiple doses, the steady-state palbociclib geometric mean area under the concentration–time curve from 0 to 24 h was 2005 ng × h/mL and maximum observed concentration was 112·3 ng/mL, similar to those obtained in Caucasian patients following the same dosing regimen. Comparisons of single dose and multiple dose pharmacokinetic data indicated linear pharmacokinetics of palbociclib. The geometric mean accumulation ratio of palbociclib exposure after multiple dose compared with single dose was 2·1, consistent with a terminal half-life of 23·4–27·5 h. Trough concentrations of letrozole were similar to concentrations obtained in Caucasian patients. No deaths or permanent discontinuations due to adverse events were reported. One serious adverse event occurred but was not considered to be treatment-related. The most common clustered adverse events were neutropaenia (n=20, 77%), leukopaenia (n=19, 73%), and anemia (n=11, 42%), with neutropaenia (n=15, 58%) and leukopaenia (n=8, 31%) the most common grade 3–4 adverse events.InterpretationNo dose adjustment for palbociclib is needed based on the Chinese population. The toxicity of palbociclib in combination with letrozole treatment was tolerable and manageable.FundingPfizer Inc.     

Safety,Efficacy, and Pharmacokinetics of Rezivertinib (BPI-7711) in Patients With Advanced NSCLC With EGFR T790M Mutation: A Phase 1 Dose-Escalation and Dose-Expansion Study

IntroductionRezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor selective for EGFR-sensitizing and T790M mutations. This study was designed to evaluate the safety, efficacy, and pharmacokinetics of rezivertinib for patients having advanced NSCLC with EGFR T790M mutation.MethodsThis phase 1 study (NCT03386955) was conducted across 20 sites in the People's Republic of China. Patients received rezivertinib at six oral dose levels (30 mg, 60 mg, 120 mg, 180 mg, 240 mg, 300 mg) once daily until disease progression, unacceptable toxicity, or patient withdrawal. The primary end points were safety for the dose-escalation phase and objective response rate by the blinded independent central review for the total study population.ResultsA total of 19 patients in dose-escalation phase using the standard 3 + 3 design principle and 153 patients in dose-expansion phase were enrolled from September 11, 2017, to August 23, 2019. The data cutoff date was on June 15, 2020. No dose-limiting toxicity occurred in the dose-escalation phase. The treatment-related adverse events were observed in 82.0% (141 of 172) of patients, and 17.4% (30 of 172) had grade greater than or equal to 3, among which decreased neutrophil count (2.9%), leukopenia (2.9%), and pneumonia (2.9%) were the most common. The overall blinded independent central review–evaluated objective response rate was 59.3% (102 of 172, 95% confidence interval: 51.6–66.7), and the median progression-free survival was 9.7 (95% confidence interval: 8.3–11.1) months.ConclusionsRezivertinib was found to have promising efficacy with a manageable safety profile in patients with EGFR T790M-mutated advanced NSCLC. Further study is warranted.     

护理人员职业倦怠与组织承诺、工作满意度的关系研究

目的研究职业倦怠与组织承诺、工作满意度的关系。方法采用整群随机抽样的方法,选取黑龙江省3家三级甲等公立医院660护理人员进行职业倦怠、组织承诺、工作满意度问卷调查。结果 (1)护理人员组织承诺、工作满意度和职业倦怠的平均分依次为(3.87±0.62)分、(3.24±0.71)分、(3.12±0.58)分,(2)工作满意度、组织承诺与职业倦怠分别为低度负相关关系,(3)福利待遇、规范承诺、排班、年龄、专业发展机会、婚姻状况、学历、家庭和工作平衡对职业倦怠的联合解释量为19.9%。结论护理人员组织承诺好工作满意度处于较高水平,职业倦怠比较严重,组织承诺、工作满意度对护理人员职业倦怠有负向预测作用。     

羊水间充质干细胞在肿瘤治疗中的研究进展

羊水间充质干细胞是多能的非造血祖细胞,具有自我修复及多向分化潜能,如成骨细胞、成软骨细胞及成脂肪细胞。尽管其具有高度增殖能力,但是其在体内并没有成瘤的报道,甚至多次传代后其核型也正常。 AF-MSCs对肿瘤的趋向性及其作为治疗多种肿瘤的细胞载体已经被很多研究证实。本文总结近期国内外的相关文献,就羊水间充质干细胞在肿瘤治疗中的研究进展进行综述。     

改良经皮肝胆囊镜入路制作初步实验研究

目的 初步探索改良经皮经肝胆囊镜入路制作的可行性和安全性.方法 4只家猪为实验动物,在超声引导下,经皮经肝胆囊穿刺引流后应用扩张器逐级将经皮穿刺道扩张,随后应用扩张球囊一次性将经肝入胆囊穿刺道扩张,扩张后立即置入可容纳胆囊镜通过的18F鞘管从而建立经皮经肝胆囊镜入路,最后通过鞘管留置球囊引流管牵拉引流.评估术中操作情况,观察动物对手术耐受情况,1周后拔除引流管,开腹观察腹腔内情况及经皮经肝胆囊入路愈合情况.结果 4只动物均顺利完成经皮经肝胆囊镜入路制作.尸检可见所有动物腹腔内无出血,无胆汁漏,腹腔脏器无粘连者3只、轻度粘连1只,穿刺局部肝脏与壁层腹膜之间紧密粘连.镜下可见肝脏窦道壁肉芽组织成熟,经皮经肝窦道愈合良好.结论 改良经皮经肝胆囊镜入路制作具有可行性及安全性.     

18F-FDG与18F-FLT PET/CT在肺结核瘤与恶性肿瘤鉴别诊断中的应用

目的：探讨18F-FDG与18F-FLT显像在诊断与鉴别肺结节尤其是肺结核与恶性肿瘤中的效能。方法：肺结节患者163例,年龄17~92岁,其中结核瘤组29例,其它良性结节组46例,恶性结节组88例,以盲法集中读片、前瞻性多中心临床研究标准方案进行18F-FDG与18F-FLT显像和读片,获得病灶最大值SUVFDG和SUVFLT并对病灶进行定量分析。结果：肺结节的最大SUVFDG及最大SUVFLT中位值均以恶性结节、肺结核、其他良性结节之序依次减低;SUVFDG、SUVFLT恶性结节组与结核组对照有显著性差异（P<0.001）;据ROC曲线分析,FDG、FLT显像SUVmax分别以5.9、2.4为界值可鉴别结核瘤与恶性结节,FLT显像诊断的灵敏度为80.68%,特异性为75.86%,准确性为79.49%,诊断效能高于FDG（P<0.001）。SUVFLT/SUVFDG比值的诊断效能高于单独FDG、FLT显像SUV值。结论：在鉴别诊断肺结核瘤与恶性结节中,FLT显像的诊断效能高于FDG显像,双示踪剂显像明显提高鉴别诊断的准确性。SUVFLT/SUVFDG比值在肺结节鉴别诊断中有重要价值。     

微波凝固治疗耳廓假性囊肿32例疗效观察

目的观察微波凝固治疗耳廓假性囊肿的疗效。方法对32例耳廓假性囊肿患者行微波凝固治疗,统计有效率。结果全部病例随访1年。微波凝固治疗耳廓假性囊肿一次治愈25例,占78%;二次治愈5例,占16%;三次治愈2例,占6%。总有效率100%。结论微波凝固治疗耳廓假性囊肿操作方便,容易掌握,创伤小,恢复快,治疗时间短,疗效满意,且无明显副作用。经过临床观察实践证实,此治疗方法行之有效。