BACKGROUND:Alternating sequential administration of drugs may be a promising approach to overcome chemotherapy resistance in advanced pancreatic ductal adenocarcinoma (PDAC). METHODS:This study was an open-label, single-arm, and prospective trial included patients with untreated advanced PDAC. They received 2 cycles of NS regimen (nab-paclitaxel:125 mg/m2, intravenously injected on days 1 and 8, plus S-1:40-60 mg, orally twice per day for 1-14 days) followed by 2 cycles of GemOx regimen (gemcitabine, intravenously injected on days 1 and 8, and oxaliplatin: 130 mg/m2, intravenously injected on day 1). The primary efficacy endpoint was a progression-free survival rate at 6 months (PFSR-6m). The secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Specific mRNA transcripts were used to explore survival associated genes. RESULTS:Forty-two patients received a minimum of one treatment cycle, and of these, 30 patients completed one alternating treatment consisting of 4 cycles. The PFSR-6m was 71% (95% CI = 58%-87%). The median PFS and OS were 6.53 months (95% CI = 6.03-8.43) and 11.4 months (95% CI = 9.8-14.4), respectively. Common grades 3-4 hematological AEs included neutropenia 30.9%, leukopenia 26.2%, anemia 2.4%, and thrombocytopenia in 11.9%. Patients with OS > 10 months showed high expression of HLA-DQA2 while melanoma-associated antigen genes (MAGE) were notably upregulated in patients with OS < 10 months. CONCLUSION:The alternating sequential administration of the NS and GemOx regimens may be a novel approach for first-line chemotherapy in patients with advanced PDAC requiring further study (ClinicalTrials.gov Identifier: ChiCTR1900024867).

胰腺癌是全球第七大致命的恶性肿瘤,分别是美国胃肠道恶性肿瘤和癌症相关死亡的第二大和第三大原因.与其他恶性肿瘤相比,晚期胰腺癌患者的生存率最低,中位总体生存率为2～8个月,5年生存率为8.5％.治疗十分困难,给临床医生带来极大挑战.目前晚期胰腺癌的治疗药物匮乏,化疗仍然是其主要治疗方法.虽然化疗能短暂的控制疾病的进展,但是在生存期的延长方面却差强人意.分子靶向治疗已在其他的瘤种中取得了里程碑般的成就,譬如肺癌、结直肠癌等,但晚期胰腺癌患者的分子靶向治疗效果并不显著.这需要我们去寻找新的治疗靶点和药物.本文基于胰腺癌信号传导通路及肿瘤微环境,总结和分析晚期胰腺癌分子治疗的研究现状,探索未来胰腺癌治疗的发展方向.

胰腺癌是消化系统恶性程度最高的肿瘤.近年来胰腺癌的发病率呈逐年上升趋势,预计在未来10年胰腺癌将成为发达国家癌症死亡的第二大原因.由于诊断时分期较晚,治疗选择有限,胰腺癌的预后极差,只有手术是治愈的唯一方法.为了提高手术切除率并改善预后,新辅助治疗已悄然成为目前胰腺癌治疗的热点问题.但现在胰腺癌的新辅助治疗还未有标准化的治疗方案,本文主要探讨胰腺癌新辅助治疗的研究现状.

目的 探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)孕妇体内丙酮醛(methylglyoxal,MGO)的表达水平及对孕妇围产期认知功能的影响.方法 收集2019年3月～2020年10月哈尔滨医科大学附属第一医院诊断并分娩的孕妇160例,分为2组:GDM组(n=80)、健康孕妇组(NP组,n=80).收集50例志愿者为对照组.采集静脉血测量糖化血红蛋白(glycosylated hemoglobin,HbA1c)和血糖水平.应用酶联免疫吸附试验(enzyme-linked immunosorbert assay,ELISA)方法检测MGO、C反应蛋白(C-reactive protein,CRP)、白细胞介素 6(interleukin-6,IL-6)、8-异前列腺素 F2α(8-iso-prostaglandin F2α,8-iso-PGF2α)、硝基酪氨酸和脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达水平.结果 GDM组中MGO、CRP、IL-6、8-iso-PGF2α、硝基酪氨酸的表达水平明显高于NP组和CG组(P＜0.05).GDM组BDNF表达水平明显低于NP组和CG组(P＜0.05).结论 GDM孕妇存在围产期认知功能减退.

恶性中胚叶混合瘤(malignant mixed mesodermal tumors,MMMTs)又称癌肉瘤,是一种罕见的恶性肿瘤病理学类型,极具侵袭性,预后差,在女性生殖道中最常发生部位是子宫[1],而发生于卵巢的癌肉瘤仅占所有卵巢癌病理学类型的1％～4％[2].现对本院2019 年收治的2 例卵巢恶性中胚叶混合瘤患者的临床资料进行分析,并结合文献复习,探讨提高恶性中胚叶混合瘤的检测手段,寻求有效的治疗方案,以提高生存率,改善预后.

409 Background:Chemotherapy is effective in mPDAC but the effect is not satisfactory. Alternate sequential treatment appears to be feasible and effective, with manageable toxicities and decreased neurotoxicity. Similar studies have not been carried out in China. Therefore, we evaluated the efficacy and safety of albumin-bound paclitaxel combined with S1, sequential and alternate gemcitabine combined with oxaliplatin in the first-line treatment of patients with mPDAC. Methods:Based on an expected 6-month PFS rate of 45% and a threshold 6-month PFS rate of 25%, a one-sided exact test is applied setting α = 0.025. The number of patients required for a power of 80% was calculated to be 24. Considering the drop rate of 15%, 30 patients need to be enrolled in the experiment. This open-label, single-arm, prospective study enrolled patients with locally advanced and metastatic pancreatic cancer, who have not received prior chemotherapy regimens and radiation therapy between Jan, 2019 and Dec, 2020. The patient receives the NS regimen first:albumin-bound paclitaxel(125mg/m 2 ) was administered for the first and eighth day by intravenous drip and S1 (40-60 mg)was administered orally twice a day for 2 cycles with 3-week cycle. Then the GEMOX regimen is applied sequentially and alternately: Gemcitabine (1000mg/m 2 , intravenous infusion for 30 minutes, administration on the first and eighth days) and oxaliplatin (130mg/m 2 , intravenous injection for 2 hours, administration on the second day) were given for 2 cycles with 3-week cycle. After that, the NS and GEMOX regimen were alternately used again. The treatment was continued until disease progression or unacceptable toxic effects. Results:In this study, 36 eligible patients received the sequential treatment of the above regimen with a median age of 59 years (range 35 to 67 years). 24 patients were eligible for efficacy analysis. Median follow up time was 8.8 months. 45.8% (11/24) of patients completed 3 alternating (8 cycles) treatment, and 33.3% (8/24) of patients completed 2 alternating (6 cycles) treatment, other patients only completed 1 alternate treatment. 6-month PFS rate was 70.8%(17/24), The median PFS of 24 patients was 8.9 months. The final OS and PFS was not yet achieved. The most common grade 3/4 treatment related AEs were thrombocytopenia (13.33%), granulopenia (8.3%), peripheral nerve toxicity (5.6%), and all adverse reactions could be recovered to less than grade 2 after suspension of medication or reduction of dose. Conclusions: The treatment of albumin-bound paclitaxel combined with S1, sequential and alternate gemcitabine combined with oxaliplatin showed promising efficacy and manageable toxicities in patients with mPDAC, and required more prospective patients to be enrolled. Clinical trial information: ChiCTR1900024867.

There is a lack of useful biomarkers for predicting the efficacy of anti–programmed death-1 (PD-1) therapy for advanced gastric and colorectal cancer. To address this issue, in this study we investigated the correlation between inflammatory marker expression and survival in patients with advanced gastric and colorectal cancer. Data for 111 patients with advanced gastric and colorectal cancer treated with anti–PD-1 regimens were retrospectively analyzed. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and clinical characteristics of each patient were selected as the main variables. Overall response rate, disease control rate, and progression-free survival were primary endpoints, and overall survival and immune-related adverse events (irAEs) were secondary endpoints. The chi-squared test and Fisher’s exact test were used to evaluate relationships between categorical variables. Uni- and multivariate Cox regression analyses were performed, and median progression-free survival and overall survival were estimated with the Kaplan–Meier method. The overall response rate and disease control rate of anti–PD-1therapy in advanced gastric and colorectal tumors were 12.61 and 66.66%, respectively. The patients with MLR < 0.31, NLR < 5, and PLR < 135 had a significantly higher disease control rate than those with MLR > 0.31, NLR > 5, and PLR > 135 ( P < 0.05). The multivariate analysis revealed that MLR < 0.31, BMI > 18.5, and anti–PD-1 therapy in first-line were associated with prolonged PFS. MLR < 0.31 and BMI > 18.5 were associated with prolonged overall survival. The irAE rate differed significantly between PLR groups, and PLR < 135 was associated with an increased rate of irAEs ( P = 0.028). These results indicate that the inflammatory markers NLR, MLR, and PLR have clinical utility for predicting survival or risk of irAEs in patients with advanced gastric cancer and colorectal cancer.

病毒性心肌炎起病隐匿且诊断困难,目前已成为儿童和青壮年患者猝死的常见病因.柯萨奇病毒B3(CVB3)对心肌细胞造成的直接损伤以及心肌细胞免疫作用共同导致了病毒性心肌炎的发生.2B蛋白是CVB3对心肌细胞造成直接损伤的一种关键蛋白,可在脂质双分子层中形成亲水性孔道,导致内质网腔内的钙离子(Ca2+)外流形成内质网应激;同时,还可减少线粒体Ca2+吸收,影响线粒体途径的细胞凋亡.因此,研究CVB3编码的2B蛋白调控Ca2+信号转导并导致线粒体途径凋亡的机制及其具有的心肌保护作用,可为CVB3诱导的病毒性心肌炎提供新的治疗靶点.

病毒性心肌炎(VMC)的常见病因为病毒感染,以柯萨奇病毒B3(CVB3)最常见.内质网在多种因素(病毒感染等)的作用下,导致错误折叠或未折叠蛋白质在内质网中聚集,产生内质网应激(ERS).ERS通过调控相关信号通路诱导细胞死亡,参与多种心脏疾病的发生发展.其可通过细胞凋亡、自噬、焦亡和铁死亡等方式促进细胞死亡,从而在VMC的病理过程中发挥重要作用.因此可通过抑制ERS的发生减轻细胞凋亡、自噬、焦亡和铁死亡,降低VMC发病率.未来通过干扰CVB3诱导ERS的信号通路,可能能为VMC的治疗提供新方法.

目的:探讨中国黑龙江地区汉族人群FK506结合蛋白5(FKBP5)基因多态性与精神分裂症的关系.方法:采用SNaPshot测序法检测和分析49例汉族精神分裂症患者(患者组)和49名汉族健康对照者(对照组)的FKBP5基因rs3800373、rs1360780、rs9296158和rs9470080位点基因型和等位基因频率.结果:FKBP5 rs3800373位点基因型频率两组间差异有统计学意义(P<0.05);Logistic回归分析显示,FKBP5基因rs3800373位点TT基因型携带者精神分裂症发生风险明显高于GT基因型携带者(95％CI:0.117～0.756,P=0.01).结论:FKBP5基因rs3800373位点基因多态性可能与中国黑龙江地区汉族人群精神分裂症发病风险有关.

胰腺癌是一种致死性极高的恶性肿瘤,其5年生存率不到8％.可行根治性手术的胰腺癌患者较未行手术者预后有显著差异,单纯的手术治疗仅能将胰腺癌5年生存率提高至10％左右,究其原因主要是单纯手术后复发、转移的几率仍然极高,且复发、转移后患者生活质量欠佳,预后极差,远期生存时间短.因此,寻求胰腺癌术后更加有效的辅助治疗药物或者方案,并进行规范、合理、综合的药物治疗,控制微转移,对防止和延迟复发意义重大,该研究领域也是近年来针对胰腺癌研究的重点方向.本文基于近年来胰腺癌术后治疗的研究进展做一综述.探索胰腺癌术后不同药物、不同治疗方案下的生存获益情况及胰腺癌术后治疗的药物发展趋势,为胰腺癌术后治疗提供有价值的参考.

骨关节炎(osteoarthritis,OA),一种常见的肌肉骨骼性疾病,是造成老年人下肢残疾的重要原因,也是造成社会经济负担最大的疾病之一,其病理表现为滑膜炎、软骨损伤、骨赘形成以及软骨下骨的重塑,常可累及手、髋、膝等多个关节.全世界大约有25％的人患OA,我国以膝骨关节炎(knee osteoarthritis,KOA)最常见[1].

阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)已被证实为脑梗死、心肌梗死等多种心脑血管疾病的危险因素,脑小血管疾病(cerebral small vessel diease,CSVD)是脑血管疾病的又一常见类型.本文对OSAHS与CSVD相关性分析的研究进展综述.

癫痫患者骨折的风险是正常人的2～6倍 [1],此类患者出现的骨质流失和骨折发生率增加还存在许多未解决的问题.过去两年发表的论文关注了抗癫痫药物(antiepileptic drugs, AEDs)对骨骼系统的影响,以及癫痫患者骨质疏松和骨折的风险.这些危险因素包括长期使用AEDs、多药联合以及女性性别等.本文综述AEDs诱导骨质减少的发病机制,并建立癫痫人群骨质疏松症的管理和预防指南 [1-11].

Purpose Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods Three hundred fifty-three patients with resectable PC and 807 patients with locally advanced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

急性心肌梗死(AMI)作为一种具有高致死率和致残率的心血管疾病,严重危害着现代人的生命健康,降低了人们的生活质量.AMI一旦发生,治愈率较低,且患者发作时极度痛苦.因此,AMI的早期诊断在临床预防、治疗以及预后方面均具有重要作用.由于疾病症状、心电图在AMI早期诊断过程中并不典型,因此AMI相关血清标志物的寻找显得尤为重要.心肌肌钙蛋白、肌红蛋白、肌酸激酶同工酶以及心型脂肪酸结合蛋白是较早释放入血的经典血清标志物,在疾病发生早期即可检测出,对于AMI早期诊断及预测均具有重要价值.

BACKGROUND AND PURPOSE:To investigate differences in the characteristics of carotid atherosclerotic plaques of symptomatic subjects in northern and southern China using MRI. METHODS:Sixty-three subjects in northern China (mean age: 59.1±8.6 years, 45 men) and 56 subjects in southern China (mean age: 60.4±8.6 years, 38 men) were included. All subjects underwent carotid artery multicontrast vessel wall MRI. Plaque morphology, calcification, lipid-rich necrotic core, intraplaque haemorrhage, luminal surface disruption and high-risk plaque were measured and identified. All plaque characteristics were compared between subjects in northern and southern China using Mann-Whitney U test or χ2 test. RESULTS:Compared with subjects in southern China, those in northern China had significantly greater areas for lumen (57.7±14.9 mm2 vs 50.4±18.3 mm2, p=0.009), wall (38.4±13.1 mm2 vs 31.9±11.7 mm2, p<0.001) and total vessel (96.1±20.2 mm2 vs 82.4±22.7 mm2, p=0.001) and mean wall thickness (1.25±0.43 mm vs 1.13±0.40 mm, p=0.019). χ2 analysis showed that subjects in northern China tended to have a higher prevalence of intraplaque haemorrhage (14.3% vs 5.4%, p=0.106) and high-risk plaque (20.6% vs 10.7%, p=0.140) than those in southern China, although these differences were not statistically significant (all p>0.05). CONCLUSION:Subjects in northern China have significantly larger vessel size and may have a higher prevalence of vulnerable plaques than those in southern China. Our findings provide additional perspective to optimise the management of cerebrovascular disease in individuals in different regions in China. TRIAL REGISTRATION NUMBER:NCT02017756.

H医院研究的绩效管理对医院的专科化建设起到积极的促进作用.作为专科肿瘤医院,H医院以病种为中心,依据医院精细化绩效管理办法,促进医院专科化建设,逐步实现专科化诊疗模式,做到"科有特色、人有专长".经过三年绩效管理,临床科室专科化率平均达到93％,科室的诊疗水平不断提升,患者的信任度与满意度显著提高,增强了医院的核心竞争力,实现了医院的可持续发展.本文对此展开研究,论述绩效管理在医院专科化建设中的探索与应用,以期有所裨益.

医院绩效管理和运营成本控制中存在一些问题,如缺乏完善的管理体制和统一控制,信息得不到有效沟通.提出了提升医院绩效管理和运营成本控制水平的措施,如建立绩效管理体制,加强运营成本控制,建立健全监管机制,积极培养专业人才.多措并举,推动医院又快又好发展.

目的:分析慢性肾小球肾炎患者血清肝细胞生长因子(HGF)、胱抑素C(Cys-C)、凝血酶激活的纤溶抑制物(TAFI)水平的变化及其临床诊断价值.方法:选择我院2017年1月～2018年5月收治的71例慢性肾小球肾炎患者作为慢性肾小球肾炎组及同期于本院进行健康体检的83例作为健康对照组.检测进而比较两组血清HGF、Cys-C、TAFI水平,分析以上指标和患者肾功能的相关性及对慢性肾小球肾炎的诊断价值.结果:慢性肾小球肾炎组血清HGF、Cys-C、TAFI水平均显著高于对照组(P＜0.05).慢性肾小球肾炎患者治疗后血清HGF、Cys-C、TAFI水平均显著低于治疗前(P＜0.05).慢性肾小球肾炎患者血清HGF、Cys-C、TAFI水平和肾功能指标(肌酐(Scr)、尿素氮(BUN)、尿酸(UA))均呈显著正相关(P均＜0.05).血清HGF水平诊断慢性肾小球肾炎的曲线下面积为0.826,敏感度和特异度分别为0.747和0.746;血清Cys-C水平诊断慢性肾小球肾炎的曲线下面积为0.821,敏感度和特异度分别为0.687和0.859;血清TAFI水平诊断慢性肾小球肾炎的曲线下面积为0.816,敏感度和特异度分别为0.855和0.647;血清HGF、Cys-C、TAFI水平联合检测诊断慢性肾小球肾炎的曲线下面积为0.951,敏感度和特异度分别为0.831和0.757.结论:慢性肾小球肾炎患者血清HGF、Cys-C及TAFI水平均明显升高,联合检测血清HGF、Cys-C及TAFI可能作为慢性肾小球肾炎诊断及预评估参考指标.