Targeted multimodal imaging modalities

Molecular imaging non-invasively visualizes and characterizes the biologic functions and mechanisms in living organisms at a molecular level. In recent years, advances in imaging instruments, imaging probes, assay methods, and quantification techniques have enabled more refined and reliable images for more accurate diagnoses. Multimodal imaging combines two or more imaging modalities into one system to produce details in clinical diagnostic imaging that are more precise than conventional imaging. Multimodal imaging offers complementary advantages: high spatial resolution, soft tissue contrast, and biological information on the molecular level with high sensitivity. However, combining all modalities into a single imaging probe involves problems yet to be solved due to the requirement of high dose contrast agents for a component of imaging modality with low sensitivity. The introduction of targeting moieties into the probes enhances the specific binding of targeted multimodal imaging modalities and selective accumulation of the imaging agents at a disease site to provide more accurate diagnoses. An extensive list of prior reports on the targeted multimodal imaging probes categorized by each modality is presented and discussed. In addition to accurate diagnosis, targeted multimodal imaging agents carrying therapeutic medications make it possible to visualize the theranostic effect and the progress of disease. This will facilitate the development of an imaging-guided therapy, which will widen the application of the targeted multimodal imaging field to experiments in vivo.     

梅毒螺旋体抗体筛查及其临床意义

目的研究梅毒螺旋体的感染状况，探讨梅毒螺旋体抗体筛查的现实意义。方法采用酶联免疫分析法（ELIsA）检测梅毒螺旋体抗体，阳性者再使用甲苯胺红不加热血清试验（TRusT）和梅毒螺旋体明胶凝集试验（TPPA）做进一步检测。结果5998例住院患者ELISA法共检测出阳性86例，TPPA法检测出阳性78例，TRUST法检测出阳性22例。高龄（〉70岁）患者的阳性检出率高于其它年龄组。结论住院患者常规筛查梅毒螺旋体抗体可有效检测出隐性梅毒患者，不仅可以早诊断、早治疗，减少医疗纠纷的发生，也可以预防院内交叉感染。     

规范转院转诊 减少医疗纠纷 提高医疗质量

首诊医疗机构及其医务人员在接诊后，在最大限度保护患者生命健康的同时，对需要转院转诊的患者，除承担法定的转诊义务外，还要严格遵守转诊程序。按照相应的法律法规，正确合理地转院转诊，对于减少医疗纠纷，提高医疗质量有着重要的意义。本文着重分析转诊转院的法定义务和规范程序，并对特殊情况的转院转诊进行探讨。     

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.     

Asiatic acid ameliorates dextran sulfate sodium-induced murine experimental colitis via suppressing mitochondria-mediated NLRP3 inflammasome activation

In the present study, the effect of asiatic acid, a natural triterpenoid compound, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of asiatic acid dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco and myeloperoxidase activity were also significantly reduced by asiatic acid treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β, IL-6 and IFN-γ, were markedly suppressed by asiatic acid. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in asiatic acid-treated mice, which suggested that the NLRP3 inflammasome activation was suppressed. In addition, we also found that asiatic acid dose-dependently inhibited IL-1β secretion, caspase-1 activation as well as inflammasome assembling in vitro. Furthermore, the mechanism of asiatic acid was related to the inhibition of mitochondrial reactive oxygen species generation and prevention of mitochondrial membrane potential collapse. Taken together, our results demonstrate the ability of asiatic acid to inhibit NLRP3 inflammasome activation and its potential usage in the treatment of inflammatory bowel diseases.     

Baicalin from the extract of Scutellaria baicalensis affects the innate immunity and apoptosis in leukocytes of children with acute lymphocytic leukemia

Scutellariae Radix (root of Scutellaria baicalensis) has a long history of application in traditional and in modern herbal medications. The major components of Scutellariae Radix are baicalin, baicalein, wogonoside and wogonin. Accumulating evidence demonstrates that Scutellaria has immunomodulatory effects and possesses compelling anticancer potential.Treatment of peripheral blood leukocytes (PBLs) with Scutellaria extract (SBE) enriched in baicalin, reduced viability of PBLs obtained from patients with acute lymphoblastic leukemia (ALL). SBE had no impact on the survival of healthy, control leukocytes. The immune system modulation by SBE resulted in increased production of IFNγ in PBLs, and reduced TNFα and IL-10 production in bone marrow cells (BMC), in ALL patients. SBE stimulated the nonspecific antiviral immunity, assessed by resistance of PBLs and BMC to vesicular stomatitis virus (VSV) infection. SBE showed pro-apoptotic activity in NALM-6 cell line (B-type human leukemia). The number of cells expressing annexin V increased from 6% in control cultures to 29% and 52% after treatment with 100 μg/ml and 200 μg/ml respectively. Increased percentage of apoptotic cells was observed when cells were treated with corresponding concentration of baicalin. SBE enhanced apoptosis of PBLs in BMC of leukemic children. The percentage of PBLs that underwent apoptosis and mean annexin V expression increased from 11% in the control to 17% and 24% for the doses of 100 μg/ml and 200 μg/ml respectively. Importantly, SBE did not induce apoptosis of PBLs in the healthy, control group.     

改良“三位一体”防护法预防脊柱机器人俯卧位手术中压力性损伤的效果

目的探讨改良“三位一体”防护法预防脊柱机器人俯卧位手术中压力性损伤(PI)的效果。方法选择行脊柱机器人椎间融合器植入植骨融合手术患者61例,随机分为观察组31例和对照组30例。观察组采用改良“三位一体”防护法,即联合使用石蜡油、经亲水助剂处理后的熔喷无纺布及硅凝胶垫;对照组采用常规方法,即联合使用液体敷料、泡沫敷料及硅凝胶垫。比较2组患者术后皮肤受压情况(包括皮肤压痕、红斑、水疱、破损等)。结果观察组头面部、左侧髋部、右侧髋部的PI发生率低于对照组,差异均有统计学意义(P<0.05)。观察组黏胶性皮肤损伤发生率为0,低于对照组的16.67%(5/30),差异有统计学意义(P<0.05)。结论脊柱机器人俯卧位手术中应用改良“三位一体”防护法能显著降低PI、黏胶性皮肤损伤发生率。     

Biomechanical analysis of fractures in the mandibular neck (collum mandibulae)

After treatment of fractures in the neck of the mandible by means of immobilization of the dentition, often more or less severe manifestations of malocclusion remain. It was hypothesized that this is caused by an altered articulation in the jaw joint on the affected side. Furthermore, it was hypothesized that an anteriorly displaced condyle, as observed frequently as a side effect of the treatment, is caused by pull of the lateral pterygoid muscle, despite maxillomandibular fixation.Intervention experiments were performed in silico to test these hypotheses. With a biomechanical model of the human masticatory system alterations were applied mimicking a fractured mandibular neck and configurations that had been observed after healing.It was predicted that the altered articulation in the jaw joint caused asymmetrical jaw movements despite symmetrical muscle activation. The jaw was predicted to close with an open bite similar to clinical observations. The predicted laterodeviations, however, were not in accordance with clinical observations. Despite maxillo-mandibular fixation the lateral pterygoid muscle was able to pull the mandibular condyle out of its fossa in anterior direction. Consequently, despite some methodological limitations, in general the predictions corroborated the hypotheses.