The effect of mesoporous bioactive glass on the physiochemical,biological and drug-release properties of poly(dl-lactide-co-glycolide) films

Poly(lactide-co-glycolide) (PLGA) has been widely used for bone tissue regeneration. However, it lacks hydrophilicity, bioactivity and sufficient mechanical strength and its acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Mesoporous bioactive glass (MBG) with highly ordered structure (pore size 2–50 nm) possesses higher bioactivity than non-mesoporous bioactive glass (BG). The aim of this study is to investigate the effect of MBG on the mechanical strength, in vitro degradation, bioactivity, cellular response and drug release of PLGA films and optimize their physicochemical, biological and drug-delivery properties for bone tissue engineering application. The surface and inner microstructure, mechanical strength and surface hydrophilicity of MBG/PLGA and BG/PLGA films were tested. Results indicated that MBG or BG was uniformly dispersed in the PLGA films. The incorporation of MBG into PLGA films significantly improved their tensile strength, modulus and surface hydrophilicity. MBG/PLGA resulted in an enhanced mechanical strength, in vitro degradation (water absorbance, weight loss and ions release), apatite-formation ability and pH stability in simulated body fluids (SBF), compared to BG/PLGA. MBG/PLGA and BG/PLGA films enhanced human osteoblastic-like cells (HOBs) attachment, spreading and proliferation compared to PLGA. HOBs differentiation was significantly upregulated when cells were cultured on 30 MBG/PLGA for 14 days, compared to 30 BG/PLGA. MBG/PLGA enhanced the accumulative release of dexamethazone (DEX) at early stages (0–200 h) compared to BG/PLGA, however, after 200 h, DEX-release rates for MBG/PLGA was slower than that of BG/PLGA. The contents of MBG in PLGA films can control the amount of DEX released. Taken together, MBG/PLGA films possessed excellent physicochemical, biological and drug-release properties, indicating their potential application for bone tissue engineering by designing 3D scaffolds according to their corresponding compositions.     

经胃造口逆向植入支架治疗食管癌性狭窄和瘘2例报道

目的方法结果结论探讨经过胃手术造口途径逆向置放食管支架治疗食管瘘的可行眭。使用手术腹壁胃造口途径经由贲门至食管逆向操作,反向置入食管被膜支架以治疗食管癌性狭窄和瘘。二例晚期食管癌患者因食管严重狭窄迂曲,引导钢丝不能经口顺向通过病变段,导致采用常规方法无法置放食管支架;后改经手术胃造口途径逆向植入食管被膜支架均获得成功,食管瘘口被完全封堵,食管狭窄解除,恢复经口进食。其中一例因高龄及原先吸入胜肺炎无法控制终至呼吸衰竭而死亡,另一例存活一年后因癌转移而死亡。经手术胃造口逆向植入食管支架方式治疗复杂食管癌性狭窄和瘘切实可行,但需要积极尽早实施方能收到最佳疗效。     

左束支区域起搏与右室间隔部起搏对房室传导阻滞患者新发房颤及心功能影响的对比

目的 探讨左束支区域起搏（LBBAP）对高心室起搏比例患者中远期新发房颤及心功能影响。方法 以因II度以上房室传导阻滞行DDD起搏器植入患者为研究对象,患者随机入组LBBAP高心室起搏比例组（LBBAPhigh组）、右室间隔部起搏（RVSP）高心室起搏比例组（RVSP-high组）、RVSP低心室起搏比例组（RVSP-low组）。随访内容包括：各随访节点心房频率大于180次/min、持续时间大于1 min且发生自动模式转换（AMS）事件、动态心电图、超声心动图参数、NT-proBNP水平。分析三组患者的临床基本特征,使用Kaplan-meier法绘制患者新发房颤的时间曲线,并采用COX比例风险模型进行多因素相关性分析。对比三组患者半年期心超参数与NTproBNP水平。结果 与LBBAP-high组比较,起搏QRS宽度RVSP-low组升高（P <0.01）,RVSP-high组升高（P<0.01）。随时间延长,患者术后新发房颤发生率逐渐增高。三组患者记录到房颤事件共有59例（57%）,其中,LBBAP-high组15例（44%）、RVSP-low组11例（38%）、RVSP...     

Left ventricular longitudinal systolic dysfunction in children with type 1 diabetes mellitus: A systematic review and meta-analysis

ObjectiveChildren with type one diabetes mellitus (T1DM) may have subclinical myocardial insults but large heterogeneity exists among the reports. This study aimed to compare myocardial strain values of the left ventricle (LV) in paediatric patients with T1DM without overt cardiac disease and healthy controls.MethodsFive databases (MEDLINE, Embase, Scopus, Web of Science and Cochrane central register of controlled trials) were searched from inception to March 30, 2020. The studies reporting two-dimensional speckle tracking echocardiography in asymptomatic T1DM paediatric patients and control groups were included. Pooled mean strain values in each group and mean difference (MD) between the two groups for LV global longitudinal strain (LVGLS) and LV global circumferential strain (LVGCS) were assessed using a random effects model.ResultsTen studies (755 T1DM and 610 control) with LVGLS were included with 6 studies having LVGCS (534 T1DM and 403 control). Patients with T1DM had overall 3 percentage points lower LVGLS than healthy subjects (18.4 %, 95 % confidence interval [17.1, 19.6] vs 21.5 % [20.3, 22.7], MD = −3.01 [−4.30, −1.71]). A similar result was seen in LVGCS (18.7 % [15.4, 22.0] vs. 21.4 % [18.1, 24.6], MD = −3.10[−6.47, 0.26]) but not statistically significant. Meta-regression identified those with higher Haemoglobin A1c (HbA1c) had worse GLS.ConclusionsSubclinical LV dysfunction among patients with T1DM occurs as early as in their childhood, while even EF is preserved. The longitudinal cardiac function is altered, but not the circumferential. GLS can be used to detect subclinical LV systolic dysfunction in paediatric population.     

Analysis of conditional survival in primary hepatocellular carcinoma after narrow-margin hepatectomy: a large-sample,dual-centre,retrospective study

BackgroundOverall survival (OS) reflects the constant hazard and survival probabilities calculated from the initial follow-up. Conditional survival (CS) dynamically estimates prognosis based on survival time after treatment. This study aimed to estimate CS in patients who had undergone narrow-margin hepatectomy for primary hepatocellular carcinoma.MethodsThe clinical data of 1010 eligible patients between 2012 and 2017 were retrospectively analysed. The equation CS1=OS(x+1)/OS(x) was used to calculate the probability of an additional 1-year survival in patients who had survived for x years.ResultsTumour differentiation, microvascular invasion, and tumour emboli were independent risk factors for OS. Actuarial survival decreased from 91.53% at 1 year after hepatectomy to 48.92% at 4 years, whereas CS1 increased from 69.45% at 1 year to 94.62% at 4 years. The difference was more obvious in the tumour-emboli subgroup, with an OS of 26.38% at 5 years versus a CS1 of 88.91% at 4 years following narrow-margin hepatectomy (Δ62.53%).ConclusionCS is potentially useful in providing a dynamic evaluation of survival, predicting prognosis more accurately than OS during follow-up, and formulating more appropriate treatment measures based on disease progression.     

Efficacy and safety of HER2-targeted therapy in patients with colorectal cancer: What should we expect from a meta-analysis?

Background and objectiveHuman epidermal growth factor receptor 2 (HER2) is an effective therapeutic target for breast and stomach cancers. However, the application of HER2-targeted therapy in colorectal cancer (CRC) remains controversial. We sought to assess the efficacy and safety of HER2-targeted therapy in CRC by performing a meta-analysis of relevant studies.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, and the ClinicalTrials.gov database to retrieve relevant studies. STATA 16 was used for the statistical analysis. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and incidence of treatment?related adverse events (TRAEs) were used as the outcome indicators analyzed by random- or fixed-effects models.ResultsA total of 267 patients from nine studies were included in this meta-analysis. The overall ORR and DCR were 27.5% (95% CI 16.8% to 39.6%) and 68.9% (95% CI 55.4% to 81.0%), respectively. No significant heterogeneity was found in PFS among these studies and the overall median PFS was 4.35 months (95% CI 3.70 to 4.99). The overall incidence of all-grade and grade 3 or higher adverse events were 93.5% (95% CI 88.4% to 97.4%) and 16.8% (95% CI 4.8% to 33.3%).ConclusionsHER2-targeted therapy was confirmed as a promising treatment for colorectal cancer, warranting further high-quality clinical randomized controlled trials to verify.     

Comparison of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy for Helicobacter pylori eradication: A randomized trial

ObjectiveOur team previously reported the use of antofloxacin-based bismuth quadruple therapy for the eradication of Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy in the first-line treatment for H. pylori infection.Methods1174 patients with H. pylori infection were randomized into three groups: 10-days and 14-days antofloxacin (ANT10 and ANT14) groups who received 10 and 14 days of antofloxacin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and antofloxacin 200 mg q.d.), 14-days clarithromycin (CLA14) group who received 14 days of clarithromycin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.). Eradication rate, antibiotic resistance and adverse events were analyzed.ResultsThe intention-to-treat (ITT) and per-protocol (PP) analyses have showed statistically different eradication rates between ANT14 group and ANT10 group (ITT p = 0.001; PP p < 0.001), but no statistical difference between ANT10 group and CLA14 group (ITT p = 0.340; PP p = 0.092). Treatment regimen, drug resistance and therapy duration were important clinical factors related to H. pylori eradication rates in multivariate logistic analysis. Longer durations had significantly higher eradication rates in patients with antibiotic-resistant strains or antibiotic-susceptible strains. The incidences of nausea and bitter taste were significantly higher in CLA group compared with ANT group (p = 0.002 for nausea; p = 0.002 for bitter taste). The ANT10 and ANT14 group had similar adverse event rates of gastrointestinal reactions.ConclusionThe study showed that the H. pylori eradication rate with ANT14 therapy was higher than that with ANT10 and CLA14 therapy without significantly increasing the rates of adverse event. 14 days of antofloxacin-based bismuth quadruple therapy may be a more effective way as the first-line treatment for H. pylori infection.     

Microtiter Plate-Based Differential Scanning Fluorimetry: A High-Throughput Method for Efficient Formulation Development

Nano/microparticles are widely used as vaccine adjuvants to improve antigen stability and enhance immune response. Conformational stability of a given protein was normally assessed using differential scanning calorimetry (DSC) for the optimization of formulation and for ensuring antigen stability in vaccine products. Here, a higher throughput version, namely the microtiter plate-based differential scanning fluorimetry (DSF) method was developed and optimized for assessing the protein thermal stability in the particulate adjuvant-adsorbed form. Using recombinant human papillomavirus (HPV) vaccine antigens, along with several model proteins, enhanced sensitivity and correlation to the well-established differential scanning calorimetry were demonstrated. Higher throughput and much smaller sample consumption (1/10 ～ 1/20 of the amount needed as compared to DSC) make the plate-based DSF a method of choice for formulation development, particularly during the early developmental phase of a project where the sample amount is usually quite limited.