Safety profile of sural nerve in posterolateral approach to the ankle joint: MRI study

The posterolateral approach to ankle joint is well suited for ORIF of posterior malleolar fractures. There are no major neurovascular structures endangering this approach other than the sural nerve. The sural nerve is often used as an autologous peripheral nerve graft and provides sensation to the lateral aspect of the foot. The aim of this paper is to measure the precise distance of the sural nerve from surrounding soft tissue structures so as to enable safe placement of skin incision in posterolateral approach. This is a retrospective image review study involving 64 MRI scans. All measurements were made from Axial T1 slices. The key findings of the paper is the safety window for the sural nerve from the lateral border of tendoachilles (TA) is 7 mm, 1.3 cm and 2 cm at 3 cm above ankle joint, at the ankle joint and at the distal tip of fibula respectively. Our study demonstrates the close relationship of the nerve in relation to TA and fibula in terms of exact measurements. The safety margins established in this study should enable the surgeon in preventing endangerment of the sural nerve encountered in this approach.     

A non-invasive model for predicting liver fibrosis in HBeAg-positive patients with normal or slightly elevated alanine aminotransferase

Early and accurate diagnosis of liver fibrosis is necessary for HBeAg-positive chronic hepatitis B (CHB) patients with normal or slightly increased alanine aminotransferase (ALT), Liver biopsy and many non-invasive predicting markers have several application restrictions in grass-roots hospitals. We aimed to construct a non-invasive model based on routinely serum markers to predict liver fibrosis for this population.A total of 363 CHB patients with HBeAg-positive, ALT ≤2-fold the upper limit of normal and liver biopsy data were randomly divided into training (n = 266) and validation groups (n = 97). Two non-invasive models were established based on multivariable logistic regression analysis in the training group. Model 2 with a lower Akaike information criterion (AIC) was selected as a better predictive model. Receiver operating characteristic (ROC) was used to evaluate the model and was then independently validated in the validation group.The formula of Model 2 was logit (Model value) = 5.67+0.08 × Age −2.44 × log10 [the quantification of serum HBsAg (qHBsAg)] −0.60 × log10 [the quantification of serum HBeAg (qHBeAg)]+0.02 × ALT+0.03 ×  aspartate aminotransferase (AST). The area under the ROC curve (AUC) was 0.89 for the training group and 0.86 for the validation group. Using 2 cut-off points of −2.61 and 0.25, 59% of patients could be identified with liver fibrosis and antiviral treatment decisions were made without liver biopsies, and 149 patients were recommended to undergo liver biopsy for accurate diagnosis.In this study, the non-invasive model could predict liver fibrosis and may reduce the need for liver biopsy in HBeAg-positive CHB patients with normal or slightly increased ALT.     

Rate and Predictors of Ineffective HIV Protection in African Men Who Have Sex with Men Taking Pre-Exposure Prophylaxis

AIDS and Behavior - We investigated the rate and predictors of ineffective HIV protection in men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP) in a prospective cohort study...     

镍钛形状记忆合金骨板形状恢复能力测试方法的研究

目的 建立镍钛形状记忆合金骨板形状恢复能力测试方法.方法 首先确定镍钛形状记忆合金骨板形状恢复能力标准评价体系需要测试相变温度、形状恢复力、形状恢复率,然后分别建立骨板相变温度、形状恢复力、形状恢复率的标准测试方法.因各企业生产的镍钛形状记忆合金骨板形状结构不同,为保证测试方法的统一性,测试采用标准试样代替,试样使用原材料与被替代产品的原材料为同一批次,机械加工处理工艺保持一致.结果 根据已上市产品技术文件,镍钛形状记忆合金骨板相变温度Af点为37℃,产品形状恢复率应大于95％.按照本文提供的相变温度、形状恢复力、形状恢复率测试方法,试样测试时恢复至原始形状相对应的温度为37℃,即镍钛形状记忆合金骨板的Af点为37℃;依据镍钛形状记忆合金骨板临床使用时的温度,将试样测试温度设置为37℃,试样在31℃～37℃温度区间恢复力数据曲线一直上升,到达峰值后趋于稳定状态,通过数据分析,峰值的恢复力数据即镍钛形状记忆合金骨板工作时的形状恢复力,试样形状恢复力测试结果平均值为64.18 N;两种试样测试形状恢复率,并计算分析数据,所有试样形状恢复率均大于95％,与厂家提供的技术文件相符合.结论 结果说明提供的镍钛形状记忆合金骨板形状恢复能力(相变温度、形状恢复力、形状恢复率)的测试标准方法,可为企业的质量监管提供依据,为监管部门提供监管指南,按照测试方法通过测试评价后可保证产品临床使用的安全性.     

In Vitro Activity and Resistance Profile of Dasabuvir,a Nonnucleoside Hepatitis C Virus Polymerase Inhibitor

Dasabuvir (ABT-333) is a nonnucleoside inhibitor of the RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) NS5B gene. Dasabuvir inhibited recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with 50% inhibitory concentration (IC₅₀) values between 2.2 and 10.7 nM, and was at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. In the HCV subgenomic replicon system, dasabuvir inhibited genotype 1a (strain H77) and 1b (strain Con1) replicons with 50% effective concentration (EC₅₀) values of 7.7 and 1.8 nM, respectively, with a 13-fold decrease in inhibitory activity in the presence of 40% human plasma. This level of activity was retained against a panel of chimeric subgenomic replicons that contained HCV NS5B genes from 22 genotype 1 clinical isolates from treatment-naive patients, with EC₅₀s ranging between 0.15 and 8.57 nM. Maintenance of replicon-containing cells in medium containing dasabuvir at concentrations 10-fold or 100-fold greater than the EC₅₀ resulted in selection of resistant replicon clones. Sequencing of the NS5B coding regions from these clones revealed the presence of variants, including C316Y, M414T, Y448C, Y448H, and S556G, that are consistent with binding to the palm I site of HCV polymerase. Consequently, dasabuvir retained full activity against replicons known to confer resistance to other polymerase inhibitors, including the S282T variant in the nucleoside binding site and the M423T, P495A, P495S, and V499A single variants in the thumb domain. The use of dasabuvir in combination with inhibitors targeting HCV NS3/NS4A protease (ABT-450 with ritonavir) and NS5A (ombitasvir) is in development for the treatment of HCV genotype 1 infections.     

The Impact of Six Annual Rounds of Mass Drug Administration on Wuchereria bancrofti Infections in Humans and in Mosquitoes in Mali

Wuchereria bancrofti prevalence and transmission were assessed in six endemic villages in Sikasso, Mali prior to and yearly during mass drug administration (MDA) with albendazole and ivermectin from 2002 to 2007. Microfilaremia was determined by calibrated thick smear of night blood in adult volunteers and circulating filarial antigen was measured using immunochromatographic card test in children < 5 years of age. Mosquitoes were collected by human landing catch from July to December. None of the 686 subjects tested were microfilaremic 12 months after the sixth MDA round. More importantly, circulating antigen was not detected in any of the 120 children tested, as compared with 53% (103/194) before the institution of MDA. The number of infective bites/human/year decreased from 4.8 in 2002 to 0.04 in 2007, and only one mosquito containing a single infective larva was observed 12 months after the final MDA round. Whether this dramatic reduction in transmission will be sustained following cessation of MDA remains to be seen.     

Increased expression of HMGB3: a novel independent prognostic marker of worse outcome in patients with esophageal squamous cell carcinoma

HMGB3, an X-linked member of the high-mobility group (HMG) superfamily of HMG proteins, has been shown to affect numerous tumorigenic progression. However, the expression and the prognostic role of HMGB3 in esophageal squamous cell carcinoma (ESCC) remained unknown. In this study, we examined the HMGB3 expression in ESCC tissues and adjacent nontumorous tissues by qRT-PCR and immuohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. The mRNA levels of HMGB3 were found to be significantly higher in tumorous tissues than in the adjacent normal tissues. We found that the HMGB3 expression was higher in tumorous tissues than in the adjacent non-tumorous tissues by immunohistochemical analysis of paired tissue specimens (P < 0.001). Moreover, there was a significant correlation between HMGB3 expression and gender (P = 0.037), clinical stage (P = 0.038), T classification (P = 0.013) and N classification (P = 0.017). Patients with higher HMGB3 expression had shorter overall survival than those with lower HMGB3 expression. Multivariate Cox analysis indicated that HMGB3 expression is an independent prognostic factor for overall survival (HR = 0.591, 95% CI = 0.379-0.793, P = 0.039). In summary, these findings demonstrate that HMBG3 may be a potential molecular marker for predicting the prognosis of ESCC patients.     

A Suppressor of Cytokine Signaling 1 Antagonist Enhances Antigen-Presenting Capacity and Tumor Cell Antigen-Specific Cytotoxic T Lymphocyte Responses by Human Monocyte-Derived Dendritic Cells

The suppressor of cytokine signaling 1 (SOCS1) has emerged as a critical inhibitory molecule for controlling the cytokine response and antigen presentation by dendritic cells (DCs), thereby regulating the magnitude of both innate and adaptive immunity. The aim of this study was to investigate whether the SOCS1 antagonist pJAK2(1001-1013) peptide can weaken or block the inhibition function of SOCS1 in DCs by evaluating the phenotype and cytokine production, antigen-presenting, and specific T-cell-activating capacities of DCs electroporated with human gastric cancer cell total RNA. Furthermore, STAT1 activation of the JAK/STAT signal pathway mediated by SOCS1 was analyzed by Western blotting. The results demonstrate that the SOCS1 antagonist pJAK2(1001-1013) peptide upregulated the expression of the maturation marker (CD83) and costimulatory molecule (CD86) of RNA-electroporated human monocyte-derived mature DCs (mDCs), potentiated the capacity of mDCs to induce T-cell proliferation, stimulated the secretion of proinflammatory cytokines, and enhanced the cytotoxicity of tumor cell antigen-specific CTLs activated by human gastric cancer cell total RNA-electroporated mDCs. Data from Western blot analysis indicate that STAT1 was further activated in pJAK2(1001-1013) peptide-loaded mDCs. These results imply that the SOCS1 antagonist pJAK2(1001-1013) peptide is an effective reagent for the enhancement of antigen-specific antitumor immunity by DCs.     

盐酸奥布卡因凝胶在经鼻肠梗阻导管置入术中的应用价值

目的探讨肠梗阻病人行经鼻肠梗阻导管置入术中应用盐酸奥布卡因凝胶的价值。方法将60例拟行经鼻肠梗阻导管置入术的肠梗阻病人按随机数字量表法分为研究组和对照组,每组各30例,研究组病人术前应用盐酸奥布卡因凝胶10 ml(30 mg)进行鼻腔麻醉及导管前端润滑,对照组病人术前于鼻腔及导管前端涂抹石蜡油进行润滑,比较两组病人的一次性置管成功率、置管时间及术后并发症发生率,并采用视觉模拟评分法(visual analogue scale,VAS)进行评分。结果研究组病人的一次性置管成功率为96.7%(29/30),对照组病人的一次性置管成功率为70.0%(21/30),差异有统计学意义(P<0.05)。与对照组比较,研究组病人置管所用时间明显减少,术中疼痛VAS评分降低,差异均有统计学意义(均P<0.05)。两组病人均未出现穿孔、出血等并发症。结论盐酸奥布卡因凝胶在肠梗阻病人行经鼻肠梗阻导管置入术中应用,提高了一次性置管成功率,减少置管所用时间,明显地减轻了病人术中的疼痛不适,未见并发症,效果满意。     

高分辨弥散加权成像在心房颤动导管消融围术期无症状脑栓塞发生的评估价值

目的比较高分辨弥散加权成像（hDWI）和常规DWI（cDWI）检测心房颤动（房颤）导管消融相关无症状性脑栓塞（ACE）的发生率及其特征。 方法连续入组2018年11月至2018年12月南京医科大学第一附属医院的32例房颤消融患者,以及上海市东方医院2019年1月至2019年2月的18例房颤消融患者。消融前24 h进行头颅高分辨率DWI检查以除外近期脑栓塞事件,消融后48 h内重复hDWI和cDWI检查。比较同一患者消融术后hDWI与cDWI中ACE的发生率、数量、大小和位置。 结果与cDWI相比,hDWI显示急性ACE的发生率更高（70%对42%,P<0.001）,ACE病灶数量明显更多（102对42,P < 0.001）,且hDWI测量的病灶尺寸较大（5.42 mm对4.21 mm,P < 0.001）。多因素回归分析显示,左心室射血分数受损（P=0.047）和术中激活凝血时间较低（P=0.003）与ACE发生相关。 结论hDWI能够更好地显示房颤消融相关ACE的发病情况及病灶特点。在评估ACE的研究中应考虑磁共振设置。