目标导向液体治疗对胸科手术患者术中氧供需平衡及术后结局影响的Meta分析

目的 系统评价目标导向液体治疗对胸科手术患者术中氧供需平衡及术后结局的影响.方法 计算机检索PubMed、Cochrane Library、VIP、CNKI、WanFang Database(建库至2019年10月),按照纳入与排除标准选择文献、评价质量并提取资料后,采用RevMan 5.3软件进行Meta分析.结果 ...     

婴幼儿先天性肥厚性幽门狭窄经口内镜下幽门肌切开术的围术期护理

总结4例经口内镜下幽门肌切开术治疗婴幼儿先天性肥厚性幽门狭窄的围术期护理经验.护理重点包括术前完善各项检查,术中密切监护患儿、及时识别并发症、注意无菌操作,术后做好常规护理、并发症的观察、管路及饮食护理、出院宣教.4例患儿平均住院(14.25±9.14)d,留置胃管(13.75±4.79)d,留置空肠营养管(16.75...     

The metabolic analysis in human aortic tissues of aortic dissection

BackgroundThe metabolic profile of human aortic tissues is of great importance. Among the analytical platforms utilized in metabolomics, LC‐MS provides broad metabolome coverage. The non‐targeted metabolomics can comprehensively detect the entire metabolome of an organism and find the metabolic characteristics that have significant changes in the experimental group and the control group and elucidate the metabolic pathway concerning the recognized metabolites. Employing non‐targeted metabolomics is helpful to develop biomarkers for disease diagnosis and disease pathology research; for instance, Aortic aneurysm (AA) and Aortic dissection (AD).AimThis study sought to describe the non‐targeted analysis of 18 aortic tissue samples, comparing between AA and AD.Material & MethodsOur experimental flow included dividing the samples into (AA, nine samples) and (AD, nine samples), SCIEX quadrupole timeofflight tandem mass spectrometer (TripleTOF) 6600+ mass spectrometer data refinement, MetDNA database analysis, and pathway analysis. We performed an initial validation by setting quality control parameters to evaluate the stability of the analysis system during the computer operation. We then used the repeatability of the control samples to examine the stability of the instrument during the entire analysis process to ensure the reliability of the results.ResultsOur study found 138 novel metabolites involved in galactose metabolism.Discussion138 novel metabolites found in this study will be further studied in the future.ConclusionOur study found 138 novel metabolites between AA and AD, which will provide viable clinical data for future studies aimed to implement galactose markers in aortic tissue analysis.     

Performance comparison of two nucleic acid amplification systems for SARS‐CoV‐2 detection: A multi‐center study

BackgroundMany rapid nucleic acid testing systems have emerged to halt the development and spread of COVID‐19. However, so far relatively few studies have compared the diagnostic performance between these testing systems and conventional detection systems. Here, we performed a retrospective analysis to evaluate the clinical detection performance between SARS‐CoV‐2 rapid and conventional nucleic acid detection system.MethodsClinical detection results of 63,352 oropharyngeal swabs by both systems were finally enrolled in this analysis. Sensitivity (SE), specificity (SP), and positive and negative predictive value (PPV, NPV) of both systems were calculated to evaluate their diagnostic accuracy. Concordance between these two systems were assessed by overall, positive, negative percent agreement (OPA, PPA, NPA) and κ value. Sensitivity of SARS‐CoV‐2 rapid nucleic acid detection system (Daan Gene) was further analyzed with respect to the viral load of clinical specimens.ResultsSensitivity of Daan Gene was slightly lower than that of conventional detection system (0.86 vs. 0.979), but their specificity was equivalent. Daan Gene had ≥98.0% PPV and NPV for SARS‐CoV‐2. Moreover, Daan Gene demonstrated an excellent test agreement with conventional detection system (κ = 0.893, p = 0.000). Daan Gene was 99.31% sensitivity for specimens with high viral load (C _t < 35) and 50% for low viral load (C _t ≥ 35).ConclusionsWhile showing an analytical sensitivity slightly below than that of conventional detection system, rapid nucleic acid detection system may be a diagnostic alternative to rapidly identify SARS‐CoV‐2‐infected individuals with high viral loads and a powerful complement to current detection methods.     

A lung cancer risk prediction model for nonsmokers: A retrospective analysis of lung nodule cohorts in China

BackgroundThe risk of lung cancer in nonsmokers is increasing; however, there are relatively few studies on the risks of lung cancer in nonsmokers.Patients and MethodsWe collected epidemiological and clinical data from 429 nonsmoking patients with lung nodules from the Affiliated Li Huili Hospital as a training cohort and 123 nonsmoking patients with lung nodules as a testing cohort. We identified variables that might be related to malignant lung nodules from 27 variables by performing least absolute shrinkage and selection operator analysis. Univariate and multivariate analyses of these variables were conducted using binary logistic regression. Significant variables were used to generate a lung cancer risk prediction model for nodules in nonsmokers.ResultsWe successfully constructed a predictive nomogram incorporating density, ground‐glass opacities, pulmonary nodule size, hypertension, plasma fibrinogen levels, and blood urea nitrogen. This model exhibited good discriminative ability, with a C‐index value of 0.788 (95% confidence interval [CI]: 0.742–0.833) in the training cohort and 0.888 (95% CI: 0.835–0.941) in the testing cohort; it was well‐calibrated in both cohorts. Decision curve analyses supported the clinical value of this predictive nomogram when used at a lung cancer possibility threshold of 18%. Ten‐fold cross‐validation indicated good stability and accuracy of the model (kappa = 0.416 ± 0.128; accuracy = 0.751 ± 0.056; area under the curve = 0.768 ± 0.049).ConclusionOur risk model can reasonably predict the risks of lung cancer in nonsmoking Chinese patients with lung nodules.     

Timing and Identification of the Cause and Treatment of a Cardiac Arrest: A Potential Survival Benefit

ObjectiveThe aim of this study was to evaluate how mobile medical teams (MMTs) search for the etiology of a cardiac arrest (CA) and to investigate the association between the discovery of etiology and patient outcome.Subjects and MethodsResuscitations of all adult patients who experienced an in- or out-of-hospital CA between 2016 and 2018 were video recorded. All video recordings were reviewed. The time to start of “cause analysis” and time to treatment by the MMT were analyzed. Also, investigations performed during etiologic evaluation were examined: heteroanamnesis, medical history-taking, clinical examinations, technical investigations, and the use of the 4Hs and 4Ts method.ResultsOf the 139 CA events included in this study, the MMTs performed etiologic evaluation in only 75% of the resuscitations, and in 20% of the evaluations, they did not use the recommended 4Hs and 4Ts method. Medical history-taking and heteroanamnesis were performed in the large majority, but often without clear cause. A presumptive etiology was found in 46.8% of out-of-hospital CAs and 65.2% of in-hospital CAs. A significant association was found between return of spontaneous circulation and the discovery of presumable etiology for out-of-hospital CAs (p < 0.001). The median time to treatment was 492 s (recommended: 130–250 s) for nonshockable rhythms and 422 s (recommended: 270–390 s) for shockable rhythms, up to twice the time advised according to the guidelines.ConclusionThe current approach for etiologic evaluation is not ideal. Further research is needed to establish a more structured and simplified approach.     

Effect of CSL112 (apolipoprotein A‐I [human]) on cholesterol efflux capacity in Japanese subjects: Findings from a phase I study and a cross‐study comparison

CSL112 (apolipoprotein A‐I [apoA‐I, human]) is a novel drug in development to reduce the risk of recurrent cardiovascular events following acute myocardial infarction by increasing cholesterol efflux capacity (CEC). This phase I study aimed to compare the pharmacokinetics (PKs), pharmacodynamics (PDs), and safety of CSL112 in Japanese and White subjects. A total of 34 Japanese subjects were randomized to receive a single infusion of CSL112 (2, 4, or 6 g) or placebo and 18 White subjects were randomized to receive a single dose of 6 g CSL112 or placebo, followed by PK/PD assessment and adverse events monitoring. In addition, PK/PD parameters were compared across the CSL112 clinical development program. Plasma exposure of apoA‐I increased in a dose‐dependent but nonlinear manner in Japanese subjects receiving a single dose of CSL112. Mean baseline‐corrected area under the curve from 0 to 72 h (AUC_0–72) increased from 840 to 6490 mg h/dl, in the 2 and 6 g cohorts, respectively, followed by dose‐dependent increase of CEC. The plasma PK profile of apoA‐I and increases in total and ATP binding cassette transporter A1 dependent CEC were comparable in Japanese and White subjects. The geometric mean ratio (Japanese:White) for plasma apoA‐I AUC_0–72 and maximum plasma concentration (C_max) was 1.08 and 0.945, respectively. Cross‐study comparison analysis demonstrated similar CSL112 exposure and CEC enhancement in Japanese and non‐Japanese subjects (including patients with cardiovascular disease) and further confirmed consistent PKs/PDs of CSL112. This study suggests CSL112 acutely enhances CEC and is well‐tolerated with no differences between Japanese and White subjects.

Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC? Cholesterol efflux, mediated by apolipoprotein A‐I (apoA‐I), removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion; impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates. CSL112 (apoA‐I, human) has been shown to enhance cholesterol efflux capacity and is being investigated as a novel therapy to reduce the risk of early recurrent CV events. Japanese ethnicity is known to confer differences in lipoprotein metabolism. WHAT QUESTION DID THIS STUDY ADDRESS? This ethno‐bridging study characterized the pharmacokinetics (PKs), pharmacodynamics, safety and tolerability of CSL112 in healthy Japanese subjects compared with healthy White subjects to identify any ethnicity‐based differences in cholesterol efflux capacity (CEC) and safety issues and determine the appropriate dose in Japanese subjects prior to inclusion in future or ongoing studies. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Japanese ethnicity confers no clinically relevant difference in CSL112 exposure and CEC compared to White populations and safety profiles were comparable between populations. This study supports the inclusion of Japanese subjects in an ongoing phase III study, investigating the impact of CSL112 on CV risk reduction post‐myocardial infarction, with no dose adjustment needed. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This study contributes to the discussion around PK differences between ethnic groups. It confirms similarity of apoA‐I exposure and CEC responses in Japanese and White populations, which warrants further investigation of this novel treatment approach to reduce the risk of early recurrent CV events.     

Electron transport properties of PtSe2 nanoribbons with distinct edge reconstructions

Edge reconstructions of two-dimensional (2D) materials play a central role in determining the electronic transport properties of nanodevices. However, it is not feasible to study the relationship between edge reconstruction and electronic properties using experimental methods because of the complexity of the experimental environment and the diversity of edge reconstruction. Herein, we have combined density functional theory (DFT) calculations and the nonequilibrium Green''s function (NEGF) method to investigate the inner physical mechanism of platinum diselenide (PtSe₂) nanoribbons, revealing distinctive negative differential resistance (NDR) behaviors in different nanoribbons with various edge reconstructions. The armchair PtSe₂ nanoribbons with different edge reconstructions are all metallic, while the zigzag PtSe₂ nanoribbons are semiconducting when the ratio of Pt to Se atoms at the edge is 1 : 2. These results reveal the internal source of the difference in the electron transport properties of PtSe₂ nanoribbons with different edge reconstructions, providing new ideas for the design of novel multifunctional PtSe₂ semiconducting and conducting electronic nanodevices with NDR properties.

Edge reconstructions of two-dimensional (2D) materials play a central role in determining the electronic transport properties of nanodevices.     

Lipidomics of cyclophosphamide 4‐hydroxylation in patients receiving post‐transplant cyclophosphamide

Biomarker‐guided dosing may improve the efficacy and toxicity of cyclophosphamide (CY); however, clinical studies evaluating their association with the area under the plasma concentration–time curve (AUC) of CY and its metabolites are time‐ and resource‐intensive. Therefore, we sought to identify lipidomic biomarkers associated with the time‐varying differences in CY formation clearance to 4‐hydroxycyclophosphamide (4HCY), the principal precursor to CY''s cytotoxic metabolite. Hematopoietic cell transplant (HCT) patients receiving post‐transplant CY (PT‐CY) were enrolled, cohort 1 (n = 25) and cohort 2 (n = 26) donating longitudinal blood samples before they started HCT (pre‐HCT), before infusion of the donor allograft (pre‐graft), before the first dose of PT‐CY (pre‐CY) and 24 h after the first dose of PT‐CY (24‐h post‐CY) which is also immediately before the second dose of CY. A total of 409 and 387 lipids were quantitated in the two cohorts, respectively. Associations between lipids, individually and at a class level, and the ratio of 4HCY/CY AUC (i.e., 4HCY formation clearance) were evaluated using linear regression with a false discovery rate <0.05. There were no individual lipids that passed control for false discovery at any time point. These results demonstrate the feasibility of lipidomics, but future studies in larger samples with multiple omic tools are warranted to optimize CY dosing in HCT.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

The old yet commonly used drug cyclophosphamide (CY) has a complex pharmacokinetic disposition. There is a paucity of information regarding the formation clearance of 4‐hydroxycyclophosphamide (4HCY), the precursor to CY’s primary cytotoxic metabolite phosphoramide mustard. To date, scientists have not been able to create a more effective or safer analog to CY or to identify a precision medicine tool consistently associated with the efficacy, toxicity, or pharmacokinetics of CY.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study addresses the question if the plasma lipidome before post‐transplant cyclophosphamide (PT‐CY) administration in hematopoietic cell transplant (HCT) patients is associated with the ratio of 4HCY/CY area under the plasma concentration–time curve (AUC).

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study shows that longitudinal collection of plasma lipidomic samples is feasible in HCT patients receiving PT‐CY. However, in this small patient population, we could not find an association of the plasma lipidome with the ratio of 4HCY/CY AUC. Furthermore, this study shows that the plasma lipidome changes over the ~21‐day period that starts before HCT to 24‐h after the first PT‐CY dose. This study is also among the first to evaluate the plasma lipidome in HCT patients.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study shows how interrogating the plasma lipidome may provide insight into the pharmacokinetics of CY and how interrogating the plasma lipidome is feasible for biomarker studies.     

Radical reaction extrusion copolymerization mechanism of MMA and N-phenylmaleimide and properties of products

Using the method of bulk reactive extrusion radical copolymerization, N-phenyl maleimide (N-PMI) and styrene (St) and methyl methacrylate (MMA) were copolymerized. Through multi-detection gel permeation chromatography, bulk copolymerization kinetic analysis, UV-Vis spectroscopy, elemental analysis, and ¹H NMR and ¹³C NMR analysis, it was found that, contrary to the classical free radical copolymerization theory, N-PMI and MMA could not only achieve copolymerization, but could even reach the level of azeotropic copolymerization. The factor that caused this change turned out to be the viscosity of the system. Secondly, through DSC, TG and GC-MS analysis, it was found that N-PMI units were randomly inserted into the molecular chain of PMMA, which greatly improved the stiffness of its molecular segments and the T_g of the copolymer; at the same time, the insertion of N-PMI units also very effectively blocked the zipper-style de-end group degradation that often occurs in PMMA. When the mass content of the N-PMI copolymer reached 10%, the T_g, initial degradation temperature and semi-degradation temperature of the copolymer increased by 19 °C, 58 °C and 47 °C, respectively. In addition, St, N-PMI can also significantly improve the processing fluidity of the PMMA copolymer, and after St participates were introduced in the copolymerization, the melt flow rate can be increased by 3.5 times. Furthermore, the copolymer not only had good mechanical properties and transparency, but also had excellent antibacterial properties against E. coli and S. aureus with only the effect of trace residual N-PMI in the copolymer. This provides an excellent reference for the preparation of antibacterial PMMA with high heat resistance, good mechanical properties and high transparency.

Using the method of bulk reactive extrusion radical copolymerization, N-phenyl maleimide (N-PMI) and styrene (St) and methyl methacrylate (MMA) were copolymerized.