莫昔沙星滴眼剂兔眼内组织分布及其药动学研究

目的:探讨莫昔沙星滴眼剂兔眼内组织分布及药动学。方法:将27只兔均分为9组,双眼滴0.2%莫昔沙星滴眼液100μL,分别于给药后0.125、0.25、0.5、1.0、2.0、3.0、4.0、6.0、8.0 h取样,采用高效液相色谱法测定泪液、角膜、房水、虹膜-睫状体、晶体和玻璃体组织中药物浓度,以3p97程序计算药动学参数。结果:泪液、角膜、房水、虹膜睫状体、晶体和玻璃体组织中最高药物浓度分别为(76.90±28.11)、(7.68±4.18)、(1.56±0.46)、(1.00±0.42)、(0.065±0.020)、(0.030±0.014)μg·g~(-1)或μg·mL~(-1);各组织中t_(1/2β)分别为(3.59±1.81)、(4.83±3.41)、(1.80±0.56)、(4.57±3.68)、(2.36±0.65)、(2.98±2.52)h; AUC_(0(?))分别为(75.95±17.57)、(10.68±1.57)、(2.30±0.44)、(2.86±0.42)、(0.74±0.38)、(0.086±0.042)μg·h·g(-1)或μg·h·mL~(-1)。结论:莫昔沙星易于渗透到眼内各组织,且有较高浓度。     

金银花的品种及临床应用分析

目的了解当前中药市场上金银花品种情况,规范金银花品种在临床上的运用。方法通过调查收集川渝两地市场金银花品种的情况,对照2005版《药典》以及《湖南省中药材标准》、《贵州省中药材标准》、《云南省药品标准》和《四川省中药材标准》等中的忍冬科植物的品种及标准,分析市售金银花的品种情况。结果金银花正品所占比例仅约为71．54％,山银花作金银花出售的约占23．34％,其他品种约占5．11％,且其他类的有4种以上,整个样品群中,还有掺杂、掺假现象。结论川渝中药市场上金银花的品种混乱,甚至有部分的掺杂冒充现象,应引起相关部门的高度重视。     

A big pertussis outbreak in a primary school with high vaccination coverage in northern China: An evidence of the emerging of the disease in China

BackgroundA big pertussis outbreak occurred in a primary school with high vaccination coverage in northern China. An investigation was carried out in order to calculate the attack rate and identify the risk factors.MethodsBetween May 12 and July 29, an investigation was carried out in the primary school, which included 383 students and 27 teachers. Three definitions were used to distinguish the cases: confirmed, epidemiologically linked and suspected cases. A total of 232 blood samples were collected and examined by ELISA among healthy children in another primary school.ResultsA total of 138 suspected pertussis cases were counted, of which 116 students were confirmed. The attack rate among students was as high as 30.29%. The pertussis outbreak lasted 88 days, and had quaternary cases of transmission. Migrant children were almost four times as likely to catch the disease as local children (p = 0.005). In addition, students who had received the last dose of pertussis vaccine more than 4 years prior were three times more likely of becoming ill than those less than 4 years (p = 0.006). The average level of antibodies to pertussis was 30.99 IU/mL among healthy children. No statistically significant difference was observed between DTaP and DTwP (p = 0.843).ConclusionsThis pertussis outbreak in a primary school with high vaccination coverage was an evidence of the pertussis resurgence in China. The major risk factor we identified was the waning of immunity in the years after pertussis vaccination. Booster vaccination for students should be given.     

我国城市地区癌症筛查项目人员对筛查工作意愿倾向的多中心调查及政策建议

目的 基于癌症筛查实际供方角度,从工作人员主观感受及意愿层面评价癌症筛查项目的可持续性。方法 2014-2015年,基于城市癌症早诊早治项目,在16个省份项目点选取2013-2015年所有承担项目的医院、CDC和社区卫生服务中心,采用纸质问卷和网络调查开展访谈,对象包括宏观管理人员、具体项目管理人员和一线工作人员等。结果 最终完成访谈4 626份,访谈对象总体认为参加项目的最大收获在于社会价值感的提升（63.6%）、当地影响力（35.9%）及专业技能提升（30.6%）等;最大困难在于社会物质激励不够所致工作积极性低（30.9%）、信息采集口径不一致（28.3%）、部门间协调（24.4%）和机构间沟通衔接困难（23.5%）等。当单项筛查服务劳务补偿约50元时,工作人员会考虑加班工作。63.7%的受访者有长期筛查服务意愿,主要原因：可通过项目提升个人/团队在当地影响口碑（48.7%）、通过项目提升个人/团队专业技能（43.1%）等;无服务意愿者主要担心工作量超负荷（59.8%）、对日常工作的干扰（49.8%）等。结论 收获与困难相关结果提示,若要长期可持续性开展癌症筛查工作,建议加强项目内荣誉激励、对外宣传及专业能力建设,根据具体情况提高劳务补偿。服务意愿结果则提示,应从政府和领导层面加强信息化建设及机构/部门间协调,机构内应合理协调筛查项目与日常工作。     

Primary site disease and recurrence location in ovarian cancer patients undergoing primary debulking surgery vs. interval debulking surgery

IntroductionThe natural history and patterns of ovarian cancer (OC) relapse are still unclear. Recurrent disease can be peritoneal, parenchymal, or nodal. This study aims to analyze the location and pattern of OC recurrence according to the primary site of disease and to the type of surgical approach used.Material and methodsAll OC patients underwent primary debulking surgery (PDS) or interval debulking surgery (IDS), with 2014 FIGO stage III-IV, and with platinum-sensitive recurrence were included in the study. Primary disease location and site of recurrences were divided into peritoneal, parenchymal, and nodal, according to the presence of peritoneal carcinomatosis, parenchymal metastasis, and nodal involvement, respectively.ResultsA total of 355 patients were initially considered; of them, 295 met the inclusion criteria. Two hundred thirty-three patients obtained no macroscopic residual tumor at the end of primary surgical treatment. Primary parenchymal disease relapsed in 84.6% cases at a parenchymal site (p < 0.001), 97.2% of peritoneal diseases relapsed on the peritoneum (p < 0.001), and 100% of nodal diseases had a nodal recurrence (p < 0.001). Stratifying by the surgical approach all these correlations have been confirmed both in the PDS (p < 0.001) and IDS (p < 0.001) groups.ConclusionOur study shows that the site of relapse in cases of platinum-sensitive OC recurrence is closely related to the primary location of the disease, regardless of the type of initial treatment. Therefore, more attention during followup should be paid to areas where the initial tumor was present.     

Transvaginal ultrasound assessment of urinary tract in gynecological oncology patients: A multicenter prospective study

IntroductionThe aim of this study was to assess the prevalence of urinary tract involvement diagnosed on transvaginal ultrasound examination in women gynecological cancers. The diagnostic performance of transvaginal ultrasound in detecting ureteral and bladder involvement was also evaluated.MethodsThis is a multicenter prospective study. Women with gynecological cancers or recurrence undergoing ultrasound examination were included. Transvaginal ultrasound is simple and non-invasive method. Ureters, vesico-uterine septum, bladder involvement were evaluated. Sensitivity, specificity, positive predictive values (PPV), negative predictive value (NPV) of ultrasound were calculated. Surgery or imaging methods (MRI or CT scan) were considered as reference standard.ResultsA total of 569 patients were enrolled and 547 of them had diagnosis of malignancy. 56/547 (10.2%) had a diagnosis of urinary tract infiltration at ultrasound examination. On ultrasound examination, both ureters were clearly visualized in the vast majority of cases (507/547, 92.7%), whereas only one ureter was identified in 21/547 (3.8%) patients and both ureters were not visualized in 19/547 (3.5%). Ultrasound examination demonstrated high specificity (>99.0%) and high NPV (>97.0%) for all ultrasound parameters; sensitivity was good for bladder wall infiltration (83.3%) and for vesico-uterine septum infiltration (80.8%), and low for right (69.23%) and left (65.4%) ureter infiltration.ConclusionsThe prevalence of pelvic urinary tract infiltration on transvaginal ultrasound examination in women with gynecologic malignancy was 10%. We believe that pelvic urinary tract assessment plays a key role during transvaginal ultrasound examination, in order to plan the management of patients with gynecologic cancers.     

Impact of neoadjuvant chemotherapy on the postoperative pathology of locally advanced cervical squamous cell carcinomas: 1:1 propensity score matching analysis

ObjectiveTo assess the impact of neoadjuvant chemotherapy on postoperative pathology for stage IB2 and IIA2 cervical squamous cell carcinoma.MethodsPostoperative pathology was compared between patients who received neoadjuvant chemotherapy followed by radical hysterectomy (NACT group) and patients who received upfront radical hysterectomy (URH group). Then, patients in the NACT group were divided into a chemotherapy-sensitive group and a chemotherapy-insensitive group according to their response to chemotherapy.ResultsAfter 1:1 propensity score matching (PSM), the positive rates of lymphovascular space invasion (LVSI) (7.9% vs 17.7%, P = 0.001) and cervical deep stromal invasion (60.4% vs 76.2%, P < 0.001) in the NACT group were significantly lower than those in the URH group, while the positive rates of parametrial invasion, lymph node metastasis, and vaginal margin invasion were not significantly different between the two groups. The rate of positive lymph node metastasis in the chemotherapy-sensitive group was significantly lower than that in the URH group (18.1% vs 26.5%, P = 0.037).ConclusionAmong patients with stage IB2 and IIA2 cervical squamous cell carcinomas, NACT can reduce the positive rate of intermediate-risk factors, such as deep cervical stromal invasion and LVSI, but cannot reduce the positive rate of high-risk factors. For patients who are chemotherapy sensitive, NACT can reduce the positive rate of lymph node metastasis.     

Efficacy of perioperative chemotherapy in resected colorectal liver metastasis: A systematic review and meta-analysis

BackgroundNearly half of patients with colorectal cancer develop liver metastases. Radical resection of colorectal liver metastases (CRLM) offers the best chance of cure, significantly improving 5-year survival. Recurrence of metastatic disease is common, occurring in 60 % or more of patients. Clinical equipoise exists regarding the role of perioperative chemotherapy in patients with resected CRLM. This investigation sought to clarify the efficacy of perioperative chemotherapy in patients that have undergone curative-intent resection of CRLM.MethodsA systematic review and meta-analysis was completed of randomized controlled trials (RCTs) comparing perioperative chemotherapy to surgery alone in patients with resected CRLM. MEDLINE (Ovid), EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched, as well as abstracts from recent oncology conferences. A meta-analysis was performed pooling the hazard ratios for disease-free survival (DFS) and overall survival (OS), using a random-effects model.ResultsA total of five, phase 3, open-label, RCTs were included resulting in a pooled analysis of 1119 of the total 1146 enrolled patients. 559 patients were randomized to perioperative chemotherapy and 560 to surgery alone. Pooled estimates demonstrated a statistically significant improvement in DFS (HR 0.71, 95 % CI: 0.61–0.82; p < 0.001) but not OS (HR 0.87, 95 % CI: 0.73–1.04; p = 0.136).ConclusionPerioperative chemotherapy in the setting of resected CRLM resulted in an improvement in DFS, however this did not translate into an OS benefit. Poor compliance to post-hepatectomy oxaliplatin-based chemotherapy regimens was identified. Further investigation into the optimal regimen and sequencing of perioperative chemotherapy is justified.     

Toxic role of prostaglandin E2 receptor EP1 after intracerebral hemorrhage in mice

Inflammatory mechanisms mediated by prostaglandins may contribute to the progression of intracerebral hemorrhage (ICH)-induced brain injury, but they are not fully understood. In this study, we examined the effect of prostaglandin E₂ receptor EP1 (EP1R) activation and inhibition on brain injury in mouse models of ICH and investigated the underlying mechanism of action. ICH was induced by injecting collagenase, autologous blood, or thrombin into the striatum of middle-aged male and female mice and aged male mice. Effects of selective EP1R agonist ONO-DI-004, antagonist SC51089, and nonspecific Src family kinase inhibitor PP2 were evaluated by a combination of histologic, magnetic resonance imaging (MRI), immunofluorescence, molecular, cellular, and behavioral assessments. EP1R was expressed primarily in neurons and axons but not in astrocytes or microglia after ICH induced by collagenase. In middle-aged male mice subjected to collagenase-induced ICH, EP1R inhibition mitigated brain injury, brain edema, cell death, neuronal degeneration, neuroinflammation, and neurobehavioral deficits, whereas its activation exacerbated these outcomes. EP1R inhibition also was protective in middle-aged female mice and aged male mice after collagenase-induced ICH and in middle-aged male mice after blood- or thrombin-induced ICH. EP1R inhibition also reduced oxidative stress, white matter injury, and brain atrophy and improved functional outcomes. Histologic results were confirmed by MRI. Src kinase phosphorylation and matrix metalloproteinase-9 activity were increased by EP1R activation and decreased by EP1R inhibition. EP1R regulated matrix metalloproteinase-9 activity through Src kinase signaling, which mediated EP1R toxicity after collagenase-induced ICH. We conclude that prostaglandin E₂ EP1R activation plays a toxic role after ICH through mechanisms that involve the Src kinases and the matrix metalloproteinase-9 signaling pathway. EP1R inhibition could be a novel therapeutic strategy to improve outcomes after ICH.