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1.
ACS Sens ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967386

ABSTRACT

Flexible pressure sensors have attracted great interest due to their bendable, stretchable, and lightweight characteristics compared to rigid pressure sensors. However, the contradictions among sensitivity, detection limit, thickness, and detection range restrict the performance of flexible pressure sensors and the scope of their applications, especially for scenarios requiring conformal fitting, such as rough surfaces such as the human skin. This paper proposes a novel flexible pressure sensor by combining the nanoengineering strategy and nanocomposite structures. The nanoengineering strategy utilizes the bending deformation of nanofilm instead of the compression of the active layer to achieve super high sensitivity and low detection limit; meanwhile, the nanocomposite structures introduce distributed microbumps that delay the adhesion of nanofilm to enlarge the detection range. As a result, this device not only ensures an ultrathin thickness of 1.6 µm and a high sensitivity of 84.29 kPa-1 but also offers a large detection range of 20 kPa and an ultralow detection limit of 0.07 Pa. Owing to the ultrathin thickness as well as high performance, this device promotes applications in detecting fingertip pressure, flexible mechanical gripping, and so on, and demonstrates significant potential in wearable electronics, human-machine interaction, health monitoring, and tactile perception. This device offers a strategy to resolve the conflicts among thickness, sensitivity, detection limit, and detection range; therefore, it will advance the development of flexible pressure sensors and contribute to the community and other related research fields.

3.
Am J Med Sci ; 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38834139

ABSTRACT

BACKGROUND: The aim of this study was to investigate the optimal CVP range in sepsis and septic shock patients admitted to intensive care unit. METHODS: We performed a retrospective study with adult sepsis patients with CVP records based on the eICU Collaborative Research Database. Multivariable logistic regression was performed to explore the associations between CVP level and hospital mortality. Non-linear correlations and optimal CVP range were explored using restricted cubic splines (RCS). RESULTS: A total of 5302 sepsis patients were included in this study. Patients in 4-8 mmHg group owned the lowest odds ratio for raw hospital mortality (19.7%). The logistic regression analyses revealed that hospital death risk increased significantly when mean CVP level exceeds 12 mmHg compared to 4-8 mmHg level. U-shaped association of CVP with hospital mortality was revealed by RCS model in septic shock patients and the optimal range was 5.6-12 mmHg. While, there was a J-shaped trend for non-septic shock patients. For non-septic shock patients, patients had an increased risk of hospital death only if CVP exceeded 11 mmHg. CONCLUSIONS: We observed U-shaped association between mean CVP level and hospital mortality in septic shock patients and J-shaped association in non-septic shock patients. This may imply that patients with different severity of sepsis have different CVP requirements. We need to monitor and manage CVP according to the circulatory status of the sepsis patient.

4.
Macromol Rapid Commun ; : e2400322, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819032

ABSTRACT

Bioinspired microdevices have made significant strides in various applications including human motion and health detection. However, facile and highly efficient fabrication approach of flexible pressure sensors remains a great challenge. Herein, inspired by the gecko's foot structure, a flexible pressure sensor with microdomes structure is fabricated by tip-assisted on-demand electrohydrodynamic jet (EHD-jet) printing method. Ascribed to the interlocking electrodes with microdome structure, 3D deformation rates are substantially enlarged. When the microdromes structure is under pressure, the resistivity of carbon nanotubes film coated on the surface of microdomes structure will change remarkably. By using the combined effect of assisted tip and ring focusing electrode, the influence and constraints on microstructure fabrication caused by substrate material and morphology are minimized. The desired uniform structures can be adjusted rapidly by changing the printing parameters and liquid properties. High length-height ratio (0.64) of microdomes enhances sensitivity, with minimum detection limit is 2 Pa and response time is 40 ms. Finally, the bionic flexible sensor indicated excellent performance in capable of detecting pressure, sound vibrations and human motion. This work presents a new method for high-efficiency fabrication micro-nano patterns for flexible sensors inspired, which could be used in wearable tech and health monitoring.

5.
Mol Biotechnol ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789715

ABSTRACT

Partially hydrolyzed guar gum (PHGG) protects against intestinal barrier dysfunction and can ameliorate some intestinal diseases. However, whether PHGG has a role in protecting intestinal barrier function (IBF) during sepsis remains unclear. This study aimed to investigate the role and probable mechanism of PHGG in the intestinal mucosa in sepsis. A rat sepsis model was constructed using cecal ligation and puncture (CLP). FITC-dextran 4 (FD-4) flux, serum inflammatory mediator levels, tight junction (TJ) levels, jejunum mucosa pathology, and epithelial intercellular junction ultrastructure were monitored to evaluate the effect of PHGG on IBF. Caco-2 monolayers were used to study the impact and mechanism of PHGG on lipopolysaccharide (LPS)-induced barrier dysfunction in vitro. The expression of zonula occludens protein-1 and occludin and the location of P65 were studied by immunofluorescence. Nuclear factor kappa B (NF-κB) and myosin light chain kinase 3 (MLCK) pathway-related protein expression was verified by quantitative reverse transcriptase polymerase chain reaction or western blotting. The results indicated that the jejunal mucosa structure was destroyed, the villi were disrupted and shortened, and neutrophil infiltration was evident in the septic rats. Compared to Sham group, spetic rats had increased Chiu's score, serum inflammatory mediator levels, and FD-4 flux but decreased TJ and gap junction density. In addition, the expression of MLCK, p-MLC, and TJ proteins and the expression of P65 in the nucleus were increased in septic rats. Furthermore, compared to those in the Control group, LPS-treated Caco-2 cells showed lower cell viability and transepithelial electrical resistance, while had higher FD-4 flux and the expression of MLCK, p-MLC, TJ proteins and P65 in the nucleus. PHGG pretreatment reversed the above effects induced by CLP or LPS treatment. Moreover, SN50, an NF-κB inhibitor, attenuated the above effects of LPS on Caco-2 cells. Overall, PHGG reduced inflammation, increased TJ protein expression and localization, and relieved damage to the TJ structure and intestinal permeability through suppression of the NF-κB/MLCK pathway. This study provides new insights into the role of PHGG in sepsis therapy.

6.
Mater Horiz ; 11(10): 2483-2493, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38477135

ABSTRACT

Liquid crystal elastomers (LCEs) blended with photothermal nanofillers can reversibly and rapidly deform their shapes under external optical stimuli. However, nanointerfacial slipping inevitably occurs between the LCE molecules and the nanofillers due to their weak physical interactions, eventually resulting in cyclic instability. This work presents a versatile strategy to fabricate nanointerfacial-slipping-restricted photoactuation elastomers by chemically bonding the nanofillers into a thermally actuatable liquid crystal network. We experimentally and theoretically investigated three types of metal-based nanofillers, including zero-dimensional (0D) nanoparticles, one-dimensional (1D) nanowires, and two-dimensional (2D) nanosheets. The toughly crosslinked nanointerface allows for remarkably promoted interfacial thermal conductivity and stress transfer. Therefore, the resultant actuators enable the realization of long-term-cyclic-stability 4D-printed flexible intelligent systems such as the optical gripper, crawling robot, light-powered self-sustained windmill, butterflies with fluttering wings, and intelligent solar energy collection system.

7.
Opt Express ; 32(2): 1421-1437, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297694

ABSTRACT

Two-photon microscopy (TPM) based on two-dimensional micro-electro-mechanical (MEMS) system mirrors shows promising applications in biomedicine and the life sciences. To improve the imaging quality and real-time performance of TPM, this paper proposes Lissajous scanning control and image reconstruction under a feed-forward control strategy, a dual-parameter alternating drive control algorithm and segmented phase synchronization mechanism, and pipe-lined fusion-mean filtering and median filtering to suppress image noise. A 10 fps frame rate (512 × 512 pixels), a 140 µm × 140 µm field of view, and a 0.62 µm lateral resolution were achieved. The imaging capability of MEMS-based Lissajous scanning TPM was verified by ex vivo and in vivo biological tissue imaging.

8.
Small ; 20(15): e2308312, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37992249

ABSTRACT

Flexible and stretchable electronics have attractive applications inaccessible to conventional rigid electronics. However, the mainstream transfer printing techniques have challenges for electronic films in terms of thickness and size and limitations for target substrates in terms of curvature, depth, and interfacial adhesion. Here a facile, damage-free, and contamination-free soap film transfer printing technique is reported that enables the wrinkle-free transfer of ultrathin electronic films, precise alignment in a transparent manner, and conformal and adhesion-independent printing onto various substrates, including those too topographically and adhesively challenging by existing methods. In principle, not only the pattern, resolution, and thickness of transferred films, but also the curvature, depth, and adhesion of target substrates are unlimited, while the size of transferred films can be as high as meter-scale. To demonstrate the capabilities of soap film transfer printing, pre-fabricated ultrathin electronics with multiple patterns, single micron resolution, sub-micron thickness, and centimeter size are conformably integrated onto the ultrathin web, ultra-soft cotton, DVD-R disk with the minimum radius of curvature of 131 nm, interior cavity of Klein bottle and dandelion with ultralow adhesion. The printed ultrathin sensors show superior conformabilities and robust adhesion, leading to engineering opportunities including electrocardiogram (ECG) signal acquisition and temperature measurement in aqueous environments.

9.
J Toxicol ; 2023: 2566754, 2023.
Article in English | MEDLINE | ID: mdl-38106638

ABSTRACT

Objective: The aim of this study was to investigate the effects of sodium hydrosulfide (NaHS) on Lipopolysaccharide (LPS)-induced cardiomyocyte injury in H9c2 cells. Methods: H9c2 cardiomyocytes cultivated with medium containing 10 µg/mL LPS were used to recapitulate the phenotypes of those in sepsis. Two sequential experiments were performed. The first contained a control group, a LPS group, and a LPS + NaHS group, with the aim to assure the protective effects of NaHS on LPS-treated cardiomyocytes. The second experiment added a fourth group, the LPS + NaHS + miR-133a-3p inhibition group, with the aim to preliminarily explore whether miR-133-3p exerts a protective function downstream of NaHS. The adenosine triphosphate (ATP) kit was used to detect ATP content; real-time quantitative polynucleotide chain reaction (qPCR) was used to measure the levels of mammalian targets of rapamycin (mTOR), AMP-dependent protein kinase (AMPK), and miR-133a-3p, and Western blot (WB) was used to detect protein levels of mTOR, AMPK, myosin-like Bcl2 interacting protein (Beclin-1), microtubule-associated protein 1 light chain 3 (LC3I/II), and P62 (sequestosome-1, sqstm-1/P62). Results: Compared with the control group, the expressions of miR-133a-3p (P < 0.001), P62 (P < 0.001), and the content of ATP (P < 0.001) decreased, while the expressions of Beclin-1 (P = 0.023) and LC3I/II (P = 0.048) increased in the LPS group. Compared with the LPS group, the expressions of miR-133a-3p (P < 0.001), P62 (P < 0.001), and the content of ATP (P < 0.001) in the NaHS + LPS group increased, while the expressions of Beclin-1 (P = 0.023) and LC3I/II (P = 0.022) decreased. Compared with the NaHS + LPS group, the expression levels of miR-133a-3p (P < 0.001), P62 (P = 0.001), and the content of ATP (P < 0.001) in the LPS + NaHS + miR-133a-3p inhibition group were downregulated, and the expression levels of Beclin-1 (P = 0.012) and LC3I/II (P = 0.010) were upregulated. The difference was statistically significant. There was no significant difference in the expression of AMPK and mTOR between groups. Conclusion: Our research demonstrated that NaHS relieved LPS-induced myocardial injury in H9c2 by promoting the expression of miR-133a-3p, inhibiting autophagy in cardiomyocytes, and restoring cellular ATP levels.

10.
In Vivo ; 37(6): 2533-2542, 2023.
Article in English | MEDLINE | ID: mdl-37905651

ABSTRACT

BACKGROUND/AIM: Acute exogenous lipoid pneumonia (AELP) is a rare disorder caused by intake of lipid formulations and is often underdiagnosed. Meanwhile, the mechanism of AELP is still underlying. MCC950, was previously found to significantly suppress the release of inflammatory cytokines IL-18 and IL-1ß. However, the effect of MCC950 on AELP induced by sewing machine oil has not been reported. MATERIALS AND METHODS: The NLRP3, NF-[Formula: see text]B p65, caspase-1 and IL-1ß expression in lung tissues were compared between a rat model of AELP and control rats using western blotting and real-time quantitative assay. Moreover, haematoxylin and eosin (H&E) staining was performed to elucidate the mechanisms by which MCC950 ameliorates sewing machine oil-induced AELP in vivo. RESULTS: MCC950 reduced the expression of NF-[Formula: see text]B p65 in the lung samples of the treatment group and further down-regulated the NLRP3 and caspase-1 levels while inhibited the production of IL-1ß. Besides, decreases in inflammatory cell infiltration in the lung were shown using H&E staining. CONCLUSION: MCC950 ameliorates sewing machine oil-induced acute exogenous lipoid pneumonia in rats through inhibition of the NF-[Formula: see text]B/NLRP3 inflammasome pathway.


Subject(s)
Inflammasomes , Pneumonia, Lipid , Rats , Animals , Inflammasomes/metabolism , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Sulfonamides/pharmacology , Caspases
11.
Environ Sci Technol ; 57(43): 16465-16476, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37801812

ABSTRACT

Deep learning models excel at image recognition of macroscopic objects, but their applications to nanoscale particles are limited. Here, we explored their potential for source-distinguishing environmental particles. Transmission electron microscopy (TEM) images can reveal distinguishable features in particle morphology from various sources, but cluttered foreground objects and scale variations pose challenges to visual recognition models. In this proof-of-concept work, we proposed a novel instance segmentation model named CoMask to tackle these issues with atmospheric magnetic particles, a key species of PM2.5. CoMask features a densely connected feature extraction module to excavate multiscale spatial cues at the single-particle level and enlarges the receptive field size for improved representation capability. We also employed a collaborative learning strategy to further improve performance. Compared with other state-of-the-art models, CoMask was competitive on benchmark and TEM data sets. The application of CoMask not only enables the source-distinguishing of magnetic particles but also opens up a new vista for machine learning applications.


Subject(s)
Magnetic Phenomena , Neural Networks, Computer , Microscopy, Electron, Transmission , Image Processing, Computer-Assisted/methods
12.
Small ; 19(33): e2208015, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37026672

ABSTRACT

Flexible pressure sensors play an increasingly important role in a wide range of applications such as human health monitoring, soft robotics, and human-machine interfaces. To achieve a high sensitivity, a conventional approach is introducing microstructures to engineer the internal geometry of the sensor. However, this microengineering strategy requires the sensor's thickness to be typically at hundreds to thousands of microns level, impairing the sensor's conformability on surfaces with microscale roughness like human skin. In this manuscript, a nanoengineering strategy is pioneered that paves a path to resolve the conflicts between sensitivity and conformability. A dual-sacrificial-layer method is initiated that facilitates ease of fabrication and precise assembly of two functional nanomembranes to manufacture the thinnest resistive pressure sensor with a total thickness of ≈850 nm that achieves perfectly conformable contact to human skin. For the first time, the superior deformability of the nanothin electrode layer on a carbon nanotube conductive layer is utilized by the authors to achieve a superior sensitivity (92.11 kPa-1 ) and an ultralow detection limit (<0.8 Pa). This work offers a new strategy that is able to overcome a key bottleneck for current pressure sensors, therefore is of potential to inspire the research community for a new wave of breakthroughs.

13.
Antimicrob Agents Chemother ; 67(5): e0172122, 2023 05 17.
Article in English | MEDLINE | ID: mdl-37022169

ABSTRACT

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.


Subject(s)
Ascitic Fluid , Critical Illness , Humans , Voriconazole/pharmacokinetics , Prospective Studies , Antifungal Agents/pharmacokinetics , Candida glabrata , Microbial Sensitivity Tests
14.
J Hepatol ; 79(2): 394-402, 2023 08.
Article in English | MEDLINE | ID: mdl-37086919

ABSTRACT

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.


Subject(s)
End Stage Liver Disease , Liver Transplantation , Reperfusion Injury , Humans , Liver Transplantation/adverse effects , Liver Transplantation/methods , End Stage Liver Disease/complications , Ischemia/pathology , Liver/pathology , Reperfusion Injury/etiology , Reperfusion Injury/prevention & control , Reperfusion Injury/pathology , Perfusion/methods , Organ Preservation/methods
15.
J Clin Med ; 12(3)2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36769564

ABSTRACT

BACKGROUND: Risk stratification plays an essential role in the decision making for sepsis management, as existing approaches can hardly satisfy the need to assess this heterogeneous population. We aimed to develop and validate a machine learning model to predict in-hospital mortality in critically ill patients with sepsis. METHODS: Adult patients fulfilling the definition of Sepsis-3 were included at a large tertiary medical center. Relevant clinical features were extracted within the first 24 h in ICU, re-classified into different genres, and utilized for model development under three strategies: "Basic + Lab", "Basic + Intervention", and "Whole" feature sets. Extreme gradient boosting (XGBoost) was compared with logistic regression (LR) and established severity scores. Temporal validation was conducted using admissions from 2017 to 2019. RESULTS: The final cohort included 24,272 patients, of which 4013 patients formed the test cohort for temporal validation. The trained and fine-tuned XGBoost model with the whole feature set showed the best discriminatory ability in the test cohort with AUROC as 0.85, significantly higher than the XGBoost "Basic + Lab" model (0.83), the LR "Whole" model (0.82), SOFA (0.63), SAPS-II (0.73), and LODS score (0.74). The performance in varying subgroups remained robust, and predictors, such as increased urine output and supplemental oxygen therapy, were crucially correlated with improved survival when interpretability was explored. CONCLUSIONS: We developed and validated a novel XGBoost-based model and demonstrated significantly improved performance to LR and other scores in predicting the mortality risks of sepsis patients in the hospital using features in the first 24 h.

16.
Front Surg ; 9: 917172, 2022.
Article in English | MEDLINE | ID: mdl-36081584

ABSTRACT

Purpose: This study aimed to determine the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in critically ill trauma patients. Methods: This retrospective study involved adult trauma patients from 335 intensive care units (ICUs) at 208 hospitals stored in the eICU database. The primary outcome was ICU mortality. The lengths of ICU and hospital stay were calculated as the secondary outcomes. The multivariable logistic regression model was used to identify independent predictors of mortality. To identify the effect of the NLR on survival, a 15-day survival curve was used. Results: A total of 3,865 eligible subjects were enrolled in the study. Univariate analysis showed that patients in the group with a higher NLR were more likely to receive aggressive methods of care delivery: mechanical ventilation, vasopressor, and antibiotics ( P < 0.001 for all). The ICU, in-hospital, and 15-day mortality rates of the four groups increased in turn (P < 0.001 for all). The multivariable logistic Cox regression model indicated that a higher NLR was an independent risk factor of ICU mortality in trauma patients. ROC analysis showed that the NLR had better predictive capacity on the mortality of patients with traumatic brain injury (TBI) than those with trauma (AUC 0.725 vs. 0.681). An NLR > 7.44 was an independent risk factor for ICU death in patients with TBI (OR: 1.837, 95% CI: 1.045-3.229) and TBI victims whose NLR > 7.44 had a 15-day survival disadvantage (P = 0.005). Conclusion: A high NLR is associated with a poor prognosis in trauma patients, even worse in patients with TBI. An NLR > 7.44 is an independent risk factor for death in patients with TBI.

17.
Pharmacotherapy ; 42(1): 23-33, 2022 01.
Article in English | MEDLINE | ID: mdl-34655497

ABSTRACT

STUDY OBJECTIVES: This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. DESIGN: Prospective pharmacokinetics study. SETTING: The intensive care unit in a tertiary-care medical center. PATIENTS: A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. METHODS: Model-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration (Cmin ) target and the free area under the concentration-time curve from 0 to 24 h (ƒAUC24 ) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24 /MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child-Pugh class A and B (CP-A/B) and Child-Pugh class C (CP-C) patients. RESULTS: A two-compartment model with first-order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child-Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP-A/B and CP-C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP-A/B patients and 50 mg q12h or 100 mg q24h for CP-C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. CONCLUSIONS: For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP-A/B and CP-C patients.


Subject(s)
Liver Diseases , Voriconazole , Administration, Intravenous , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacokinetics , Critical Illness , Dose-Response Relationship, Drug , Humans , Liver Diseases/drug therapy , Microbial Sensitivity Tests , Prospective Studies , Voriconazole/administration & dosage , Voriconazole/pharmacokinetics
18.
J Chemother ; 34(4): 272-276, 2022 Jul.
Article in English | MEDLINE | ID: mdl-34904531

ABSTRACT

The pharmacokinetics (PK) of several drugs including antimicrobials might be highly altered during extracorporeal membrane oxygenation (ECMO) therapy. We present the change of voriconazole (VRC) PK during ECMO in a critically ill patient who received intravenous VRC at a maintenance dose of 200 mg every 12 h for empirical antifungal therapy. Two PK profiles were drawn before and after the initiation of ECMO therapy. Though the trough levels (both C0 and C12) with ECMO were slightly lower than that without ECMO (12.58 and 12.84 vs. 14.02 µg/mL), the peak levels and the area under the concentration-time curve from 0 h to 6 h (AUC0-6) were comparable (16.36 vs. 16.06 µg/mL and 90.78 vs. 91.45 µg·h/mL, respectively), indicating that VRC plasma exposure during ECMO therapy did not greatly decrease in our patient. The circuit factors including the type of membrane should be taken into account to further identify the effects of ECMO on the PK of VRC.


Subject(s)
Extracorporeal Membrane Oxygenation , Administration, Intravenous , Antifungal Agents/pharmacokinetics , Antifungal Agents/therapeutic use , Critical Illness/therapy , Humans , Voriconazole/therapeutic use
19.
Infect Genet Evol ; 95: 105082, 2021 11.
Article in English | MEDLINE | ID: mdl-34520874

ABSTRACT

This study was to find out novel miRNAs whether could be used as diagnostic or prognostic biomarkers in sepsis. We used miRNAs microarray assays and further confirmed the levels of miRNAs in 151 septic patients' plasma. 56 miRNAs were up-regulated and 74 miRNAs down-regulated in septic patients compared with the healthy volunteers. But only miR-519c-5p and miR-3622b-3p were up-regulated in both septic and septic shock patients. The levels of miR-519c-5p and miR-3622b-3p were statistically higher in 151 septic patients than healthy controls on day 1. The AUC for miR-519c-5p was 0.79 (95% CI, 0.688-0.892, p = 0.001) in the diagnosis of sepsis, and the AUC for miR-3622b-3p 0.752 (95% CI, 0.622-0.881, p = 0.003). The AUC for the combination of these two miRNAs was 0.831 (95% CI, 0.74-0.923, p < 0.001). Besides, the AUC for miR-519c-5p was 0.597 (p = 0.043) in predicting 28-day mortality. MiR-519c-5p, miR-3622b-3p were novel biomarkers for diagnosing septic patients. High miR-519c-5p levels suggest a worse short-term prognosis. CLINICAL TRIAL REGISTRATION INFORMATION: Name of the registry: Diagnostic and prognostic value of circulating miRNA in patients with sepsis; Trial registration ID: ChiCTR-DDD-17013150; registered 30 October 2017; http://www.chictr.org.cn/edit.aspx?pid=22528&htm=4.


Subject(s)
Circulating MicroRNA/blood , Diagnostic Tests, Routine/methods , Sepsis/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers/blood , China , Female , Humans , Male , Middle Aged , Prognosis , Young Adult
20.
Micromachines (Basel) ; 12(5)2021 May 12.
Article in English | MEDLINE | ID: mdl-34066297

ABSTRACT

In this paper, surface acoustic wave (SAW) sensors containing porous graphene/PVDF (polyvinylidene fluoride) molecularly imprinted sensitive membrane for DMMP gas detection were investigated. A 433 MHz ST-cut quartz SAW resonator was used to convert gas concentration changes into frequency shifts by the sensors. The porous graphene/PVDF film was fabricated on the sensor's surface by using the tape-casting method. DMMP molecules were adsorbed on the porous structure sensing film prepared by the 2-step method to achieve the specific recognition effect. The sensitivity of the sensor could reach -1.407 kHz·ppm-1. The response time and recovery time of the SAW sensor with porous graphene/PVDF sensing membrane were about 4.5 s and 5.8 s at the concentration of 10 ppm, respectively. The sensor has good anti-interference ability to most gases in the air.

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