高龄初产妇妊娠结局探讨

目的：分析35岁以上高龄初产对妊娠结局的影响。方法：回顾性分析2000年1月-2004年12月在我院分娩的52例35岁以上高龄单胎初产妇（观察组），并选择同期分娩的104例30岁以下单胎初产妇（对照组）作为对照，比较两组孕妇妊娠期糖尿病、妊娠高血压疾病、早产、低体重儿及剖宫产发生率的差异。结果：高龄组妊娠合并糖尿病、妊娠高血压疾病、早产、低体重儿及剖宫产的发生率均显著高于对照组（P〈0．05），两组新生儿畸形率及围产儿死亡率差异无显著性。结论：高龄孕妇合并症与并发症明显增加，剖宫产率升高，应当避免高龄妊娠。     

FOLFOX4新辅助化疗方案治疗进展期胃癌效果观察

目的观察FOLFOX4新辅助化疗方案在进展期胃癌综合治疗中的作用。方法50例临床确诊的进展期胃癌患者分为2组,对照组30例采用外科手术加辅助化疗,观察组20例采用FOLFOX4为主的新辅助化疗-手术-术后辅助化疗),观察新辅助化疗对进展期胃癌的作用和毒性反应并比较2组无肿瘤残留(Residual 0,R0)切除率,手术并发症发生率和生存率。结果观察组20例对FOLFOX4化疗方案耐受较好,完全缓解2例(10%),部分缓解12例(60%),总有效率(CR+PR)为70%,18例(90%)完成了R0切除;对照组30例中有19例(63.3%)完成了R0切除;2组患者R0切除率相比较差异有统计学意义(P<0.05);术后并发症发生率相比差异无统计学意义(P>0.05);观察组与对照组的生存率比较无统计学意义(P>0.05)。结论FOLFOX4新辅助化疗方案毒性反应较低,能提高进展期胃癌R0切除率,不增加手术并发症,未能提高进展期胃癌患者的生存率。     

鸦胆子油乳联合肝动脉插管治疗肝癌124例临床观察

目的 观察鸦胆子油乳联合肝动脉插管化疗栓塞术(TACE)治疗中晚期原发性肝癌的临床疗效及毒副作用.方法 124例确诊为原发性肝癌患者随机分为治疗组和对照组,治疗组用鸦胆子油乳注射液联合肝动脉插管化疗栓塞(TACE)术和对照组单纯TACE术治疗,比较两组在实体瘤疗效、生活质量、毒副反应方面的差别.结果 治疗组在实体瘤疗效、生活质量上明显优于对照组(P＜0.05),同时毒副作用明显低于对照组(P＜0.05).结论 鸦胆子油乳联合TACE术治疗,可提高原发性肝癌疗效、改善症状,值得临床上进一步研究.     

吉西他滨联合顺铂或氟尿嘧啶治疗晚期胰腺癌临床疗效比较

目的:观察吉西他滨联合顺铂(GP方案)与吉西他滨联合氟尿嘧啶(GF方案)治疗晚期胰腺癌近期疗效和毒副作用的差异。方法:经病理组织学或细胞学证实的60例胰腺癌患者,按照随机对照的原则分为GP组和GF组,各30例。GP组给予吉西他滨1000mg/m~2加生理盐水100ml,静脉滴注30min,第1、8、15天;顺铂40mg,静脉点滴,第15、16、17天。GF组给予吉西他滨1000mg/m~2加生理盐水100ml,静脉滴注30min,第1、8、15天,氟尿嘧啶500mg/m~2加5％葡萄糖液(GS)500ml,静脉点滴6h以上,第1～5天。结果:GP组部分缓解(PR)3例,微效(MR)5例,稳定(NC)12例,进展(PD)5例,PR+MR达32.0％,中位生存期8.7个月,临床受益率(CBR)57.7％,肿瘤标志物CA19-9下降>50％为48.1％。GF组PR3例,MR8例,NC9例,PD4例,PR+MR达45.8％,中位生存期10.1个月,CBR82.1％,CA19-9下降>50％为53.6％。两组经统计学比较,CBR差异有显著性(P<0.05)。主要毒性反应为白细胞减少和血小板减少。结论:吉西他滨联合氟尿嘧啶以及吉西他滨联合顺铂,较以往单药方案疗效高,副作用少,中位生存期长,CBR高;GP方案和GF方案比较,后者的CBR更高。     

5FU局部多点注射联合TP方案用于宫颈局部晚期癌术前新辅助化疗的临床研究

目的:探讨5-FU宫颈局部多点注射联合TP方案用于晚期宫颈癌新辅助化疗的疗效和安全性。方法:选择2007年10月～2012年3月住院治疗的60局部晚期宫颈癌患者,分为实验组与对照组,实验组38例给予5-FU局部多点联合TP方案术前新辅助化疗后手术,对照组22例给予TP方案后行手术治疗。对两组术后病理、毒副反应、临床疗效进行比较。结果:实验组患者CR、PR分别为(12,31.58%)、(21,55.26%),总有效率为(33,86.84%)。对照组患者CR、PR分别为(2,9.1%)、(11,50%),总有效率为(13,59.1%)。毒副反应两组相当,经对症处理后都能耐受。结论:5-FU宫颈局部多点注射联合TP方案进行术前新辅助化疗后患者最大肿瘤直径缩小明显,毒副反应并未明显增加,是一种安全有效的治疗方法。     

Expansion of CD3+CD8+PD1+ T lymphocytes and TCR repertoire diversity predict clinical responses to adoptive cell therapy in advanced gastric cancer

The adoptive cell therapy (ACT) and delivery of ex vivo activated cellular products, such as dendritic cells (DCs), NK cells, and T cells, have shown promise for the treatment of gastric cancer (GC). However, it is unknown which cells can improve patient survival. This study was focused on the antitumour activity of a subset of these cellular products and their relationships with clinical outcomes. Nineteen patients were enrolled at the Capital Medical University Cancer Center, Beijing Shijitan Hospital, from June 1, 2013, to May 30, 2016. CD8⁺PD1⁺ T-cell sorting was carried out using flow cytometry, and the T-cell receptor (TCR) repertoire during ex vivo expansion for 15 days was analyzed by next-generation sequencing. After 15 days of culture, the number of CD8⁺ T cells had increased significantly, and the number of CD4⁺ T cells had increased correspondingly. After ex vivo expansion, CD8⁺ T cells exhibited significantly enhanced expression of PD-1, LAG-3, and TIM-3 but not 4-1BB. Survival analysis showed that patients with a pro/pre value of CD8⁺PD-1⁺ T cells >2.4 had significantly favorable overall survival (OS) (median OS time, 248 days versus 96 days, P=0.02) and progression-free survival (PFS) (median PFS time, 183 days vs. 77 days, P=0.002). The sorted CD8⁺PD-1⁺ T cells displayed enhanced antitumor activity and increased IFN-γ secretion after coculture with autologous tumor cell lines. TCR repertoire diversity was decreased after ex vivo expansion, which decreased the Shannon index and increased the clonality value. The prognosis of patients was significantly improved and was associated with the extent of CD8⁺PD-1⁺ T-cell expansion. In summary, this study showed that after ex vivo expansion for 15 days, CD8⁺PD-1⁺ T cells could be identified as tumor-reactive cells in patients treated for GC. Changing TCR species can predict the extent of CD3⁺CD8⁺PD1⁺ T-cell growth and the effect of ACT treatment.     

实验性糖尿病大鼠肺组织晚期糖基化终末产物、肺表面活性物质蛋白质A免疫组织化学分析

Objective To approach the changes of advanced glycosylated end products (AGEs),surfactant proteins A (SP-A) in the lung of experimental diabetic rats and their relationship. Methods 48 male SD rats were divided into diabetes mellitus (DM) group and control group, each group with 24 rats.The DM rat model was made by injecting streptozocin (60mg/kg) into caudal vein. The rats were killed and the lung was individually taken out at the end of 4, 12 and 20 weeks after the models were established. The changes of AGEs, SP-A in rats lung were observed with immunohistochemical assay and the images were analyzed( black is minimum of gray, white is maximum of gray ). Results We observed a great quantity of AGEs positive cells in the alveolar epithelial cells, bronchial mucosal epithelium, angio-endothelial cell and smooth muscle cells of the DM rats. The average gray (AG) was inferior to that of the controls(4weeks 93.92 ± 7.92 vs 104. 75 ± 8. 20; 12 weeks 76. 25 ± 6. 76 vs 93.50 ± 7.56; 20 weeks 47.63 ± 7.96 vs 142. 38 ± 19. 76; P ＜0. 05) and decreased with the DM course. In the 4 weeks DM rats, there were a few SP-A positive cells in the type Ⅱ alveolar epithelial cells, Clara cells and alveolar macrophage cells. In the 12 and 20 weeks DM rats, there were a great many CTGF and TGF-β1 positive cells. The AG was inferior to that of the controls( 12 weeks 75.63 ± 6. 70 vs 110. 50 ± 13.20;20 weeks 47.38 ± 4. 84 vs 97. 25 ± 9. 87; P ＜ 0. 01 ). Conclusion With the progress of diabetes, DM rats' pulmonary alveolar type Ⅱ cells injury appeared, that might be related with the deposition of AGEs.     

环磷酰胺5-氟脲嘧啶和表阿霉素联合新辅助化疗方案治疗局部晚期乳腺癌的临床研究

目的:评估环磷酰胺、5-氟脲嘧啶和表阿霉素联合新辅助化疗方案在局部晚期乳腺癌治疗中的临床疗效和毒副反应。方法:2003年1月~2006年12月50例经空芯针活检组织学诊断证实的局部晚期乳腺癌患者在术前接受新辅助化疗方案,环磷酰胺600mg/m2(第1d),5-氟脲嘧啶500mg/m2(第1d),表阿霉素50mg/m2(第1d),每3周为1个疗程,共3个疗程。结果:治疗原发病的临床有效率为76%,其中20%(10/50)达到临床完全缓解(cCR),56%(28/50)达到临床部分缓解,疾病稳定(SD)20%(10/50),疾病进展4%(2/50)。最常见的毒性反应包括中性粒细胞减少症,脱发和恶心呕吐,共有10例患者(20%)发生3~4度中性粒细胞减少症。无因新辅助化疗引起的败血症和死亡病例。结论:环磷酰胺、5-氟脲嘧啶和表阿霉素的联合新辅助化疗方案在局部晚期乳腺癌治疗中疗效显著且耐受性良好。     

Immune checkpoint inhibitors in head and neck squamous cell carcinoma: A systematic review of phase-3 clinical trials

BACKGROUNDThe outcomes of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal. A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors (ICIs). The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIMTo evaluate the evidence on the effectiveness of ICIs in HNSCC, based on published phase-3 clinical trials.METHODSWe searched PubMed, Cochrane Library, Embase, and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC (R/M HNSCC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC). We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma, recurrent, metastatic, locally advanced, immunotherapy, immune checkpoint inhibitors, monoclonal antibodies, programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T- lymphocyte associated protein-4 (CTLA-4), and phase-3 clinical trial. A sensitive search filter was used to limit our results to randomized controlled trials.RESULTSFive phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far: Four in R/M HNSCC and one in LAHNSCC. In patients with R/M HNSCC, anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care (standard single-agent systemic therapy). While the net gain in overall survival (OS) with nivolumab was 2.4 mo [hazard ratio (HR) = 0.69, P = 0.01], that with pembrolizumab was 1.5 mo (HR = 0.80 nominal P = 0.0161). The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T- lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes. In the first-line setting, in R/M HNSCC, pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo (HR = 0.77, P = 0.0034) in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive (combined positive score > 20) population compared to standard of care (EXTREME regime). In patients with PD-L1 positive R/M HNSCC, monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME. In LAHNSCC, immunotherapy using avelumab (an anti-PD-L1 agent) along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSIONAnti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings, with acceptable toxicity profiles compared to standard therapy. There is no proven efficacy in the curative setting to date.     

Repetitive milrinone therapy in ambulatory advanced heart failure patients

BackgroundAdvanced heart failure (HF) patients usually poorly tolerate guideline‐directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short‐term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up‐titrate GDMT and improve functional class.HypothesisRepetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients.MethodsAdvanced HF patients treated with beta‐blockers and implanted with defibrillators were initiated with repetitive, intermittent short‐term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B‐natriuretic peptide (BNP) levels, and echocardiography parameters.ResultsThe cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286−3768] to 631 [278−1378] pg/ml, p = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV (p = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change.ConclusionsIn this small cohort of advanced HF, repetitive, intermittent, short‐term milrinone therapy was found to be safe and potentially efficacious.