新型净水剂WS-F和MR实验室降氟试验研究

目的 探讨WS-F和MR高分子絮凝剂降氟改水的前景。方法 用自配高氟水和高氟区压把井中取来的高氟水进行室内混凝沉淀模拟试验。结果 用WS-F和MR对自配水(含氟置2．0-7．5mg／L)和高氟区取来的天然井水(含氟量1．15-10．07mg／L)进行降氟试验，都可使被处理的水氟含量控制在饮用水标准以内。结论 本方法降氟能控制处理水的氟含量，有应用前景。     

舒血管药和缩血管药选择性动脉三管介入治疗食管静脉曲张出血的临床研究

采用舒血管药酚妥拉明（Ｐｌ）、硝酸甘油（ＮＧ）和缩血管药垂体后叶素（ＶＰ）三管介入治疗食管静脉曲张出血（ＥＶＢ）３２例（Ⅰ组），并与ＶＰ肠系膜上动脉输注３１例（Ⅱ组）和ＰＬ、ＶＰ静脉滴注２４例（Ⅲ组）进行疗效对比。结果：三组总有效率分别为９６．９％、５８．１％，７０．８％。Ⅰ组疗效明显优于Ⅱ组（Ｐ＜０．０５）和Ⅲ组（Ｐ＜０．０５）。副作用发生率Ⅰ组低于Ⅱ组（Ｐ＜０．０５），而与Ⅲ组相近（Ｐ＞０．０５）。提示舒、缩血管药介入治疗ＥＶＢ疗效确实，副作用少。并对其治疗机理作了探讨。     

Advantages of CT nano-contrast agent in tumor diagnosis: A retrospective study

The purpose of this retrospective study was to explore the advantages of computed tomography (CT) nano-contrast agent in tumor diagnosis.A total of 100 patients with malignant tumor who were diagnosed in Shaanxi Province Public Hospital between January 2018 and January 2019 were included in this retrospective study. They were randomly divided into observation and control groups with 50 patients in each group. The patients in the observation group used new type of nano-contrast agent for examination, and the patients in the control group used traditional iohexol contrast agent for examination. The detection rate, misdiagnosis rate, and incidence of adverse reactions were observed. In addition, single photon emission computed tomography or CT scan was performed on patients to observe the radioactive concentration.The detection rate was 100% in the observation group and 84% in the control group, and the difference between the 2 groups was statistically significant (χ² = 8.763, P = .001). The incidence of adverse reactions was 2% in the observation group and 30% in the control group, and the difference between the 2 groups was significantly different (χ² = 12.683, P = .000). The radioactive concentration in the observation group was markedly higher than that in the control group (t = 19.692, P = .001).The use of CT nano-contrast agent in tumor diagnosis had higher detection rate of tumor and radioactive concentration, and it had lower misdiagnosis rate and adverse reaction rate than traditional iohexol contrast agent.     

左西孟旦治疗心衰的临床研究进展

左西孟旦（levosimendan,LS）是一种新型钙增敏剂,其正性肌力作用主要通过增加心肌肌钙蛋白对Ca2＋的敏感性和开放细胞膜上ATP敏感的K＋通道,增加心肌收缩力,同时扩张外周血管和冠状动脉,减轻心脏前后负荷。LS目前主要用于治疗急性和顽固性心力衰竭（HF）。国内外指南已将其列为IIa类（B级证据）,为HF的药物治疗增加了选择。     

抗结核药物引起的副作用综合报告

目的了解各种抗结核药物引起的副作用并掌握一般处理原则。方法直接或间接证明６２例中由抗结核药物引起的副作用，观察并分析各种副作用分布情况、出现时间及表现形式。结果过敏反应频度占副作用的首位，共３７例，占６０％；严重副反应绝大多数由利福霉素类引起；副作用出现时间多为服药后２个月以内；药物服用过量易导致副反应发生；多种药物可同时或相继产生严重副作用。结论一旦发生严重药物副作用，必须立即停药，及时治疗，否则后果严重；利福霉素类药停药后再服，有可能加重过敏反应程度，故要详细询问既往用药情况，对有肝炎史、酗酒史、药物过敏史和年老体弱者用药过程中要严密观察；对多种药物过敏者，无论反应轻重，以快停药、早脱敏为原则；必须确定过敏原时，要使用常量的１／１０以下，并制定应急处理措施，严重过敏者不应进行重复验证     

Optimal strategy of systemic treatment for unresectable pancreatic neuroendocrine tumors based upon opinion of Japanese experts

Background/objectivesA number of therapeutic agents have been reported to be clinically useful for the management of the patients with unresectable pancreatic neuroendocrine tumors (PanNETs) including somatostatin analogues, molecular-targeted agents and cytotoxic agents. However, the optimal strategy for selection among those treatment modalities above in these patients has remained unexplored.MethodsJapanese experts for PanNET discussed and determined the optimal treatment strategies according to the results of previously reported studies.ResultsThe tumor volume of liver metastases and the Ki-67 labeling index were unanimously accepted as indicators of the tumor burden and tumor aggressiveness, respectively, which are two most clinically pivotal factors for determining the strategy of systemic treatment for unresectable PanNETs. In addition, for those with a relatively small tumor burden and slow disease progression, somatostatin analogues were selected as the first-line treatment agents. For those with a relatively large tumor burden and rapid tumor progression, cytotoxic agents were selected, possibly aiming at tumor shrinkage. For those of intermediate tumor volume and/or growth rate, molecular-targeted agents were selected as the first choice. Based on this strategy discussed among the experts, we tentatively prepared a MAP for proposing optimal treatment strategy and examined its validity in some patients with unresectable PanNETs. Results validated the usefulness of this MAP proposed for patients harbouring unresectable PanNETs.ConclusionWe herein propose a tentative MAP for optimal treatment selection for the patients harbouring unresectable PanNETs. Further large scale studies are, however, warranted to validate the usefulness of this MAP proposed in this study.     

A meta-analysis of the risk of total cardiovascular events of isosmolar iodixanol compared with low-osmolar contrast media

BackgroundThe iso-osmolar contrast agent iodixanol may be associated with a lower incidence of cardiac events than low-osmolar contrast media (LOCM), but previous trials have yielded mixed results.ObjectiveTo compare the risk of total cardiovascular events of the iso-osmolar contrast medium, iodixanol, to LOCM.MethodsMedical literature databases were searched to identify comparisons between iodixanol and LOCM with cardiovascular events as a primary endpoint. A random-effects model was used to obtain pooled odds ratio (OR) for within-hospital and 30-day events.ResultsA total of 2 prospective cross-sectional studies and 11 randomized controlled trials (RCTs) (covering 6859 subjects) met our criteria. There was no significant difference in the incidence of within-hospital and 30-day cardiovascular events when iodixanol was compared with LOCM, with pooled OR of 0.72 (95%CI 0.49–1.06, p = 0.09) and 1.19 (95%CI 0.70–2.02, p = 0.53), respectively. Subgroup analysis showed no relative difference when iodixanol was compared with ioxaglate (OR = 0.92, 95%CI 0.50–1.70, p = 0.80) and iohexol (OR = 0.75, 95%CI 0.48–1.17, p = 0.21). However, a reduction in the within-hospital cardiovascular events was observed when iodixanol was compared with LOCM in the RCT subgroup (OR = 0.65, 95%CI 0.44–0.96, p = 0.03). Sensitivity analyses revealed that three studies had a strong impact on the association of within-hospital cardiovascular events between iodixanol and LOCM. Meta-regression analysis failed to account for heterogeneity. No publication bias was detected.ConclusionsThis meta-analysis demonstrates that there is no conclusive evidence that iodixanol is superior to LOCM overall with regard to fewer cardiovascular events.     

12例嗜麦芽窄食单胞菌感染及其药敏研究

目的：研究嗜麦芽窄食单胞菌引起的感染危险因素及有效抗生素,方法分析１２例嗜麦芽窄食单胞菌感染的临床资料,应用Ｓｃｅｐｔｏｒ系统测定了１８株嗜麦芽窄食单胞菌对２０种抗性素的敏感度。结果嗜麦芽窄食单胞菌多见于呼吸道染,其次为菌血症及局部感当了菌株对大多数抗生素耐药,结论严重基础疾病,应用广谱抗生素及免疫抑制剂是嗜麦芽窄食单胞菌感染的危险因子,替卡西林、环丙沙星和阿米卡星为抗嗜麦芽窄食单胞菌有相对活性的     

溶栓药物的研究现状及发展趋势

血栓性疾病是西方富裕国家人类死亡的主要原因,严重危害着人类健康。动脉血栓性疾病可导致急性心肌梗死（AMI）、中风;静脉血栓性疾病可导致深静脉栓塞（DVT）和肺栓塞（PE）。这类疾病主要危害心、脑、肺的血管系统,使成年人死亡或残疾。在美国,每年大约有20万人死于PE;在我国,每年超过200万人死于心脑血管疾病,每年需要进行溶栓治疗的患者超过300万。全世界有血栓患者1500万,所需溶栓剂的潜在市场约20亿美元。     

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function,activatable immunoconjugates

Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photocytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of “tumor-targeted, activatable photoimmunotherapy” in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease.Metastatic disease remains the main cause of cancer-related death despite advances in cytoreductive surgery and chemotherapy (1–4). An ongoing dilemma is the lack of options to address residual micrometastases that escape standard treatments and detection by current imaging technologies (3). In addition to spread via hematogenous and lymphatic routes (5), diffuse micrometastatic spread throughout anatomical cavities is also problematic, including peritoneal dissemination resulting from cancers of the colon (6), pancreas (7), and ovary (1, 2, 4). These obstacles are pronounced in the treatment of epithelial ovarian cancer (EOC), a prime example of a frequently recurrent disease characterized by residual micrometastases. Due to the lack of screening methods or distinct symptoms during early progression, the vast majority of EOC cases are diagnosed once the disease has metastasized and formed numerous nodules studding the peritoneal cavity (1, 2, 4). Although a significant fraction of patients (∼35%) appear to achieve a complete response after cytoreductive surgery and follow-up chemotherapy, a small number of cells with intrinsic or acquired resistance are responsible for recurrence and poor survival (1, 2, 4, 8). These residual micrometastases are clinically occult until gross recurrence, which is often refractory to standard treatments (1, 2, 4). Laparotomy, an invasive surgical reassessment, frequently fails to detect residual disease (9) while noninvasive clinical imaging modalities also have poor sensitivity for subcentimeter tumors (10, 11).To address the challenges associated with treating and detecting occult, residual, and drug-resistant micrometastases before gross recurrence, it is necessary to develop (i) targeted treatments with high tumor selectivity and distinct mechanisms of cell death (12–14) to overcome dose-limiting toxicities and chemoresistance; and (ii) high-resolution approaches with sufficient contrast to monitor microscopic disease. Here, we address both of these needs by developing an activatable construct targeted to markers overexpressed by cancer cells with dual functionality for both therapy and imaging, and integrate this into a quantitative fluorescence microendoscopy platform for longitudinal monitoring of micrometastases. This approach realizes treatment selectivity and imaging fidelity at the microscale.Targeted agents carrying “always-on,” unquenched chromophores have emerged for targeted therapy and imaging at the macroscale. In a promising clinical study, intraoperative visualization of EOC nodules labeled with a targeted, always-on fluorescent probe facilitated the identification of more tumor deposits by surgeons compared with conventional bright-field illumination (15). This development may ultimately translate to fluorescence-guided resection for more radical cytoreductive surgery, leaving less disease behind (15–17). Photoimmunotherapy (PIT) using always-on immunoconjugates is a targeted form of photodynamic therapy—first reported in the seminal works of Levy and colleagues (18)—that has been shown to hold promise by us (19–23) and by others (18, 24, 25). Because photodynamic agents are mechanistically distinct from traditional treatment modalities (13, 14), are effective against radioresistant and chemoresistant cells (19, 20, 26), and can also resensitize resistant cells to chemotherapy (20, 23), the development of PIT is of importance for overcoming drug resistance. In fact, photodynamic therapy has been used in the treatment of disseminated peritoneal disease with some success intraoperatively (27) and endoscopically in the lung, bladder, and esophagus (SI Text, Note S1).Integrating the concepts of targeted therapy and imaging, a recent proof-of-concept study performed dual epidermal growth factor receptor (EGFR)-targeted PIT and imaging of localized, macroscopic tumors using always-on immunoconjugates (25). This study used a mouse model derived from s.c. implantation of A431 squamous-cell carcinoma cells that express abnormally high levels of EGFR (25). A limitation of PIT is persistent phototoxicity and background signal in nontarget tissues due to unbound and circulating always-on immunoconjugates, which compromise treatment and imaging selectivity at the microscale. It therefore remains uncertain whether PIT is safe and effective for treatment of micrometastases—the ultimate test of treatment selectivity. It is also unknown whether always-on immunoconjugates have sufficient tumor selectivity for treatment and imaging of tumors that express more realistic levels of the target molecule. Given these limitations, we sought to develop a more selective type of PIT—termed tumor-targeted, activatable PIT (taPIT)—and tumor imaging based on dual-function immunoconjugates that enable activatable, near-infrared (NIR)-mediated PIT as well as activatable fluorescence imaging (Fig. 1). This approach—building on the concept of lysosome-activated imaging probes suggested by Achilefu, Urano, Kobayashi, and coworkers (28, 29)—not only achieves greater treatment selectivity than always-on PIT but also enables resolution of microscopic tumor deposits.Open in a separate windowFig. 1.Concepts of tumor-targeted, activatable photoimmunotherapy (taPIT) and longitudinal monitoring of micrometastases in vivo. (A) Cet-BPD—a dual-function, activatable immunoconjugate for both taPIT and monitoring of micrometastases—consists of multiple BPD molecules conjugated to each cetuximab molecule. The BPD molecules remain self-quenched until EGFR binding and cellular internalization. (B) Schematic of Cet-BPD intracellular activation. (C) taPIT enables tumor-confined phototoxicity, whereas always-on agents and immunoconjugates result in nonspecific damage to normal tissues. (D) Mouse model of micrometastatic epithelial ovarian cancer (EOC) and fluorescence microendoscopy schematics. (E) (Left) In vivo fluorescence microendoscopy of control no-tumor and EOC mice on days 5 and 14 posttumor inoculation. (Right) Corresponding ex vivo immunofluorescence images show human EOC and mouse endothelial cells (ECs) stained with anti-CK8 and -CD31 antibodies, respectively. (Scale bars: 100 μm.) Note that all images in this report are displayed on a linear scale deliberately without saturation. Nonlinear, saturated image display appears to show higher contrast, but such a representation is not quantitative (Fig. S1). (F) Schematic of i.p. Cet-BPD photoactivation using a diffusing tip fiber and scattering media to enable efficient, targeted wide-field treatment of micrometastatic disease spread throughout the abdominal cavity by stepwise irradiation of each quadrant within the cavity.Here, we demonstrate these concepts of dual-function, tumor-targeted activatable immunoconjugates for selective treatment and quantitative, longitudinal imaging of micrometastases in vivo using a clinically motivated model of advanced-stage ovarian carcinomatosis (30). In this model, peritoneal micrometastases are derived from human EOC cells (OVCAR5) that possess intrinsic resistance to chemotherapy (8, 31). Using activatable immunoconjugates, a custom-built microendoscope (32) and a newly developed image analysis workflow (Figs. S2 and S3), we present minimally invasive, quantitative, and repeated measurements of micrometastases during therapy. Using fluorescence microendoscopy to characterize immunoconjugate pharmacokinetics and to monitor micrometastatic burden reduction in vivo, we demonstrate tumor-selective immunoconjugate activation and taPIT efficacy. This targeted activation significantly reduces nonspecific phototoxicity and fluorescence to provide therapeutic response monitoring of microscopic tumor nodules in a complex model of disseminated disease.     

Bisoprolol,a once-a-day beta-blocking agent for patients with mild to moderate hypertension

The 24-h blood pressure control of bisoprolol, a new beta₁-selective, beta-blocking agent, was studied in 240 mild to moderate hypertensive patients in this 4-week, randomized, double-blind, placebo-controlled trial. A once-daily dosing schedule was evaluated by comparing bisoprolol's antihypertensive effectiveness and safety at 24 h postdose and 3 h postdose, the latter time intended to correspond to peak effectiveness. Results from this trial demonstrated the antihypertensive effectiveness of once-daily bisoprolol at doses ranging from 5-20 mg. Mean reductions from baseline diastolic blood pressure, measured 24 h postdose, were 6.3,8.8, and 10.1 mmHg for patients receiving bisoprolol 5, 10, and 20 mg, respectively, compared with 1.6 mmHg for placebo-treated patients (p< 0.01); mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6, 8.6, and 10.9 mmHg, respectively, versus 3.3 mmHg for placebo (p≤0.01); and mean reductions from baseline heart rate for the bisoprolol groups were 5.1,7.1, and 10.2 beats/min, respectively, compared with a 0.9 beats/min increase in heart rate for the placebo group (p < 0.01). The response rates for bisoprolol-treated patients ranged from 47 to 70% compared with 18% for patients on placebo (p < 0.01). Antihypertensive effects were dose-related and sustained over the 24-h dosing interval. Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial. The antihypertensive effects of bisoprolol were accompanied by a favorable safety profile. Furthermore, bisoprolol was welltolerated and did not differ significantly from placebo in either the frequency or severity of reported adverse experiences. Withdrawal rates for adverse events were 1.4% for the placebo group versus 1.9% for the composite bisoprolol group. Laboratory changes generally were related to small increases within the normal range and were not clinically relevant. No bisoprolol-treated patient left the study or interrupted treatment for a clinical laboratory abnormality.     

Delayed effusive pericarditis and recurrent pleural effusion after radiation treatment for Hodgkin's disease responsive to per os doxycycline

We present our experience with a patient with effusive pericarditis and recurrent pleural effusion that first developed 23 yr after radiation treatment for the nodular sclerosis type of Hodgkin's disease. Extensive diagnostic work up including pericardial and pleural biopsy, excluded any other cause (than radiation) of the recurrent pleural effusion. Pericarditis and pleural effusion were not controlled with regimens including steroid and non-steroid anti-inflammatory agents. The fluid collections improved only with per os doxycycline (100 mg twice a day). Four episodes of recurrent pleural effusions were also controlled with per os doxycycline. Although the concentration of doxycycline in the pericardial and pleural fluid when given orally is smaller compared with that achieved by direct installation of the agent, the fact that all episodes of pleural effusion improved with an agent commonly used for pleurodesis is intriguing.     

不同免疫抑制剂联合雄激素治疗儿童重型再生障碍性贫血

22例重型再生障碍性贫血（SAA）患儿分为三组，分别应用环孢菌素A（CSA） 康力龙、大剂量丙种球蛋白（HDIG） CSA 康力龙、抗胸腺细胞球蛋白（ATG） CSA HDIG 康力龙进行治疗观察，对比各方案近、远期疗效。结果：22例患儿经治疗后随访6个月～6年，18例存活，近期总有效率为81.8%（18/22）。各方案疗效对比，方案Ⅱ优于方案I及Ⅲ；而可评定远期疗效的10例患儿其总有效率为70%（7/10），各方案疗效则为方案Ⅲ优于方案Ⅱ及I。认为：方案I疗效安全、可靠、有效，但起效慢；方案Ⅲ疗效虽高，但ATG所致血清病反应较重，尤影响近期疗效，且花费较大；方案Ⅱ疗效肯定，起效快，无严重不良反应，较经济，可视为目前治疗小儿SAA的最佳方案。     

血小板白细胞聚集体与抗血小板治疗

在黏附分子的作用下,血小板和白细胞之间形成血小板白细胞聚集体(PLA)。PLA在动脉粥样硬化血栓形成性疾病的发生发展中有重要作用。临床研究发现,在此类疾病中PLA明显增加。不同的抗血小板药物对PLA形成的影响有所差异,监测PLA有助于指导抗血小板药的临床应用和筛选。     

Cellulose Pads (Hydrotin-C): A New Solid Coupling Agent

Objectives: Hydrotin-C is a bacterial cellulose consisting of 90% of physiological solution. The cellulose pad is smooth and elastic and cannot be torn, and is therefore suitable for use on any local skin condition. The aim of this study was to evaluate the image quality (IQ) and transducer pressure of Hydrotin-C-Pads as a solid coupling agent compared with standard coupling gel. Methods: To date, transthoracic echocardiography has been performed in 51 patients (ongoing study) using standard coupling gel and Hydrotin-C-Pads. The IQ was categorized as follows: 1 = excellent, 2 = good, 3 = poor, 4 = inadequate. All patients were questioned about the transducer pressure, which was categorized as: 0 = less, 1 = equal, 2 = more. The body mass index (BMI) was documented for all patients. Results: The IQ was very good with Hydrotin-C-Pads. The IQ was better in 84% of all patients. In patients with a BMI of over 25 and in patients with a BMI of over 30, Hydrotin-C-Pads was also better compared with standard gel. The transducer pressure was lower in 33 patients. Conclusions: Hydrotin-C-Pads can be used as a solid ultrasonic coupling agent. Because of the consistent thickness of the coupling zone, the IQ seems to be better for Hydrotin-C-Pads compared with standard coupling gel. The transducer presser is lower, and these pads are easy to apply and are reusable and reduce the burden of clean-up after treatment.