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1.
Digit Biomark ; 5(2): 167-175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34723069

RESUMO

Introduction: Difficulty swallowing (dysphagia) occurs frequently in patients with neurological disorders and can lead to aspiration, choking, and malnutrition. Dysphagia is typically diagnosed using costly, invasive imaging procedures or subjective, qualitative bedside examinations. Wearable sensors are a promising alternative to noninvasively and objectively measure physiological signals relevant to swallowing. An ongoing challenge with this approach is consolidating these complex signals into sensitive, clinically meaningful metrics of swallowing performance. To address this gap, we propose 2 novel, digital monitoring tools to evaluate swallows using wearable sensor data and machine learning. Methods: Biometric swallowing and respiration signals from wearable, mechano-acoustic sensors were compared between patients with poststroke dysphagia and nondysphagic controls while swallowing foods and liquids of different consistencies, in accordance with the Mann Assessment of Swallowing Ability (MASA). Two machine learning approaches were developed to (1) classify the severity of impairment for each swallow, with model confidence ratings for transparent clinical decision support, and (2) compute a similarity measure of each swallow to nondysphagic performance. Task-specific models were trained using swallow kinematics and respiratory features from 505 swallows (321 from patients and 184 from controls). Results: These models provide sensitive metrics to gauge impairment on a per-swallow basis. Both approaches demonstrate intrasubject swallow variability and patient-specific changes which were not captured by the MASA alone. Sensor measures encoding respiratory-swallow coordination were important features relating to dysphagia presence and severity. Puree swallows exhibited greater differences from controls than saliva swallows or liquid sips (p < 0.037). Discussion: Developing interpretable tools is critical to optimize the clinical utility of novel, sensor-based measurement techniques. The proof-of-concept models proposed here provide concrete, communicable evidence to track dysphagia recovery over time. With refined training schemes and real-world validation, these tools can be deployed to automatically measure and monitor swallowing in the clinic and community for patients across the impairment spectrum.

2.
Cell Rep ; 37(5): 109931, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731621

RESUMO

N-type voltage-gated calcium (CaV) channels mediate Ca2+ influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and nociceptive transmission. Here, we elucidate a cryo-electron microscopy (cryo-EM) structure of the human CaV2.2 complex in apo, ziconotide-bound, and two CaV2.2-specific pore blockers-bound states. The second voltage-sensing domain (VSD) is captured in a resting-state conformation, trapped by a phosphatidylinositol 4,5-bisphosphate (PIP2) molecule, which is distinct from the other three VSDs of CaV2.2, as well as activated VSDs observed in previous structures of CaV channels. This structure reveals the molecular basis for the unique inactivation process of CaV2.2 channels, in which the intracellular gate formed by S6 helices is closed and a W-helix from the domain II-III linker stabilizes closed-state inactivation. The structures of this inactivated, drug-bound complex lay a solid foundation for developing new state-dependent blockers for treatment of chronic pain.

3.
Phytomedicine ; : 153845, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34785106

RESUMO

BACKGROUND: Alcoholic liver disease (ALD), one of the most prevalent forms of liver disease, has received wide attention worldwide. However, limited efficient and appropriate therapeutic agents were responded to ALD. Isoliquiritigenin (ISL), a flavonoid isolated from liquorice, possesses multiple pharmacological activities. PURPOSE: The current study investigated the hepatoprotective effect of ISL against ALD and further elucidate the involvement of miR-23a-3p/peroxisome proliferative activated receptor-γ coactivator 1 alpha (PGC-1α) in vivo and in vitro experiments. STUDY DESIGN AND METHODS: In the study, H&E and Oil Red O staining were employed to detect liver histopathological changes and the accumulation of lipid droplets. Quantitative real-time PCR, bioinformatics, luciferase assay, immunofluorescence staining, reactive oxygen species (ROS), Western blot, and siRNA were used to further explore the mechanism of ISL protection. RESULTS: ISL significantly reduced the liver-to-body weight ratios and biochemical index. The staining results showed that ISL remarkedly ameliorated the histopathological changes in the liver. Furthermore, ISL promoted fatty acid metabolism via induction in the expression of PGC-1α-target genes PPARα, CPT1α, and ACADs, and inhibited the ROS, TNF-α, IL-1ß, and IL-6 expression. Bioinformatics and Luciferase assay analysis confirmed that miR-23a-3p might bind to PGC-1α mRNA in ALD. Significantly, the expression of miR-23a-3p was increased in the ALD, which was significantly decreased by ISL. In addition, the miR-23a-3p inhibitor also promoted lipid metabolism in ALD via PGC-1α activation. CONCLUSIONS: We first demonstrated that ISL could alleviate ALD, and further verified that ISL exerted protective effects through modulating miR-23a-3p/PGC-1α-mediated lipid metabolism in vivo and in vitro.

4.
JAAD Int ; 5: 19-32, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34816131

RESUMO

Introduction: Pruritus is a common symptom across various dermatologic conditions, with a negative impact on quality of life. Devices to quantify itch objectively primarily use scratch as a proxy. This review compares and evaluates the performance of technologies aimed at objectively measuring scratch behavior. Methods: Articles identified from literature searches performed in October 2020 were reviewed and those that did not report a primary statistical performance measure (eg, sensitivity, specificity) were excluded. The articles were independently reviewed by 2 authors. Results: The literature search resulted in 6231 articles, of which 24 met eligibility criteria. Studies were categorized by technology, with actigraphy being the most studied (n = 21). Wrist actigraphy's performance is poorer in pruritic patients and inherently limited in finger-dominant scratch detection. It has moderate correlations with objective measures (Eczema and Area Severity Index/Investigator's Global Assessment: rs(ρ) = 0.70-0.76), but correlations with subjective measures are poor (r2 = 0.06, rs(ρ) = 0.18-0.40 for itch measured using a visual analog scale). This may be due to varied subjective perception of itch or actigraphy's underestimation of scratch. Conclusion: Actigraphy's large variability in performance and limited understanding of its specificity for scratch merits larger studies looking at validation of data analysis algorithms and device performance, particularly within target patient populations.

5.
Medicine (Baltimore) ; 100(45): e27711, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766574

RESUMO

ABSTRACT: The effect on degenerative thoracolumbar kyphosis (DTLK) after short-segment instrument for lumbar spinal stenosis syndrome (LSS) remains controversial. Based on the biomechanics and compensatory of the global spino-pelvic alignment, it was assumed that the interference on the lumbar spine, instead of the thoracolumbar segment, could still make a difference on the proximal spine.To explore whether DTLK could improve with only surgery for LSS and identify influencing factors on postoperative TLK.The study was performed from January 2016 to December 2018. Sixty-nine participants (25 male) diagnosed LSS with DTLK were enrolled and surgery was only for LSS. Radiological parameters included TLK, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope, and osteoporosis. Clinical outcomes were visual analogue scale and Oswestry disability index. According to lower instrumented vertebrae (LIV) on L5 or S1, inter-group comparisons were performed between LIV on L5 (L5 group) and S1 (S1 group).Demographics were well-matched between L5 and S1 group with a mean follow-up of 24.3 ±â€Š12.1 (m). TLK improved with a mean of 16.2 ±â€Š7.6 (°) (P < .001). There was no significance on radiological and clinical parameters between L5 and S1 groups except for a larger pelvic tilt in S1 group (P = .046). Visual analogue scale (P = .787) and Oswestry disability index (P = .530) were both indifferent between normal TLK and DTLK at last (P > .05). Postoperative TLK was affected by osteoporosis and sacral slope, the latter was dominated by pelvic incidence and pelvic rotation. Osteoporosis was the risk factor for TLK correction (P = .001, odd risk = 9.58).DTLK decreased if instrument only performed for LSS, where TLK and clinical outcomes are comparably affected whether L5 or S1 is selected as LIV. This study supplements the compensatory mechanism of spino-pelvic alignment, especially for cases with severe osteoporosis.

6.
Phys Chem Chem Phys ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755737

RESUMO

Using first principles, we theoretically investigate the strain manipulation of the ultrafast spin-flip processes on the Ni@B80 endohedral fullerene by using highly correlated quantum chemical calculations. It is shown that the ultrafast local spin flip on Ni@B80 can be achieved via Λ processes with high fidelities in both the equilibrium and distorted structures. Moreover, the applied strain on Ni@B80 can significantly lead to the redistribution of spin density, and therefore dominate the spin-flip processes. It is interesting that the strain effects on the spin-flip processes of Ni@B80 are not identical. Specifically, when a strain is applied along the direction across the Ni atom, the influence is exactly opposite to the case when the strain direction goes without crossing the Ni atom. This orientation-dependent strain effect is also demonstrated by analyzing the modulated energy gaps between the singly occupied molecular orbital (SOMO) and the lowest unoccupied molecular orbital (LUMO) of the system. The present results shed some light on the mechanical control of the magneto-optic dynamics behavior of the endohedral fullerenes, and further provide the idea that strain engineering and spin engineering can be combined for the design of nanoscale magnetic storage units and spintronic devices.

7.
Elife ; 102021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643180

RESUMO

Bin/Amphiphysin/RVS (BAR) domain proteins belong to a superfamily of coiled-coil proteins influencing membrane curvature in eukaryotes and are associated with vesicle biogenesis, vesicle-mediated protein trafficking, and intracellular signaling. Here we report a bacterial protein with BAR domain-like activity, BdpA, from Shewanella oneidensis MR-1, known to produce redox-active membrane vesicles and micrometer-scale outer membrane extensions (OMEs). BdpA is required for uniform size distribution of membrane vesicles and influences scaffolding of OMEs into a consistent diameter and curvature. Cryogenic transmission electron microscopy reveals a strain lacking BdpA produces lobed, disordered OMEs rather than membrane tubules or narrow chains produced by the wild type strain. Overexpression of BdpA promotes OME formation during planktonic growth of S. oneidensis where they are not typically observed. Heterologous expression results in OME production in Marinobacter atlanticus and Escherichia coli. Based on the ability of BdpA to alter membrane architecture in vivo, we propose that BdpA and its homologs comprise a newly identified class of bacterial BAR domain-like proteins.

8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(5): 1003-1009, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34713669

RESUMO

Bionic untethered micro-nano robots, due to their advantages of small size, low weight, large thrust-to-weight ratio, strong wireless mobility, high flexibility and high sensitivity, have very important application values in the fields of biomedicine, such as disease diagnosis, minimally invasive surgery, targeted therapy, etc. This review article systematically introduced the manufacturing methods and motion control, and discussed the biomedical applications of bionic untethered micro-nano robots. Finally, the article discussed the possible challenges for bionic untethered micro-nano robots in the future. In summary, this review described bionic untethered micro-nano robots and their potential applications in biomedical fields.


Assuntos
Biônica , Robótica , Desenho de Equipamento , Procedimentos Cirúrgicos Minimamente Invasivos , Movimento (Física)
9.
Neuroimage ; 244: 118632, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34627977

RESUMO

PURPOSE: A phase correction method for high-resolution multi-shot (MSH) diffusion weighted imaging (DWI) is proposed. The efficacy and generalization capability of the method were validated on both healthy volunteers and patients. THEORY AND METHODS: Conventionally, inter-shot phase variations for MSH echo-planar imaging (EPI) DWI are corrected by model-based algorithms. However, many acquisition imperfections are hard to measure accurately for conventional model-based methods, making the phase estimation and artifacts suppression unreliable. We propose a deep learning multiplexed sensitivity-encoding (DL-MUSE) framework to improve the phase estimations based on convolutional neural network (CNN) reconstruction. Aliasing-free single-shot (SSH) DW images, which have been used routinely in clinical settings, were used for training before the aliasing correction of MSH-DWI images. A dual-channel U-net comprising multiple convolutional layers was used for the phase estimation of MSH-EPI. The network was trained on a dataset containing 30 healthy volunteers and tested on another dataset of 52 healthy subjects and 15 patients with lesions or tumors with different shot numbers (4, 6 and 8). To further validate the generalization capability of our network, we acquired a dataset with different numbers of shots, TEs, partial Fourier factors, resolutions, ETLs, FOVs, coil numbers, and image orientations from two sites. We also compared the reconstruction performance of our proposed method with that of the conventional MUSE and SSH-EPI qualitatively and quantitatively. RESULTS: Our results show that DL-MUSE is capable of correcting inter-shot phase errors with high and robust performance. Compared to conventional model-based MUSE, our method, by applying deep learning-based phase corrections, showed reduced distortion, noise level, and signal loss in high b-value DWIs. The improvements of image quality become more evident as the shot number increases from 4 to 8, especially in those central regions of the images, where g-factor artifacts are severe. Furthermore, the proposed method could provide the information about the orientation of the white matter with better consistency and achieve finer fibers delineation compared to the SSH-EPI method. Besides, the experiments on volunteers and patients from two different sites demonstrated the generalizability of our proposed method preliminarily. CONCLUSION: A deep learning-based reconstruction algorithm for MSH-EPI images, which helps improve image quality greatly, was proposed. Results from healthy volunteers and tumor patients demonstrated the feasibility and generalization performances of our method for high-resolution MSH-EPI DWI, which can be used for routine clinical applications as well as neuroimaging research.

10.
Orthop Surg ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34672095

RESUMO

OBJECTIVE: Publications on hidden blood loss (HBL) after posterior lumbar interbody fusion (PLIF) for lumbar spine stenosis syndrome (LSS) have been reported, but the modified HBL (mHBL) was different from HBL obtained by classical formula and there are few studies on lumbar spine hemorrhage with rheumatoid arthritis (RA). Therefore, the aim of our study is to respectively evaluate the importance of hidden blood loss (HBL) and modified HBL (mHBL) after posterior lumbar interbody fusion (PLIF) in patients diagnosed with LSS and RA, to explore the correlation between RA activity and HBL as well as mHBL. METHODS: A total of 61 patients (nine males and 52 females) diagnosed with LSS and RA who underwent PLIF were included. Data contained demographics, RA-related parameters such as duration of RA, Steinbrocker classification (used to evaluated RA activity), the disease-modifying anti-rheumatic drugs (DMARDs), osteoporosis and total knee arthroplasty; operation and hemorrhage parameters. Then HBL and mHBL were calculated by Gross formula and modified formula, respectively. Subgroup analysis on HBL and mHBL was performed based on gender, age (≤60 years and ˃60 years), different number of surgical segments (single segment, double segment, and ≥3 segments), and taking DMARDs or not. ANOVA analysis was performed on HBL and mHBL in different surgery segment number and Steinbrocker classification of RA. Independent sample t-test was used in comparison of gender and age, as well as in comparison between HBL and mHBL based on whether the patient took DMARDs or not. Furthermore, paired t-test was used to compare the volume between HBL and mHBL. RESULTS: The mean age and duration of RA was 65.2 ± 9.3 years and 14.3 ± 10.7 years, respectively. There were 13 grade I cases, 34 grade II cases, and 14 grade III cases as assessed by Steinbrocker classification and the most common anti-RA drugs were DMARDs (57.4%). The mean intraoperative bleeding, drainage, and blood loss in drainage (DBL) was 453.3 ± 377.8 mL, 489.1 ± 253.8 mL, and 304.6 ± 156.3 mL, respectively. There was no difference on HBL and mHBL in gender. HBL and mHBL was larger in patients over 60 years (P = 0.040 and P = 0.023). There were differences in intraoperative blood loss, drainage, and DBL based on different number of segments but not in HBL and mHBL, or on Steinbrocker classification. DBL was lower in DMARDs group than non-drugged group (P = 0.03), while HBL and mHBL were both of no significance. The comparison of HBL and mHBL showed statistical difference (P < 0.001), suggesting that mHBL volume is larger than HBL. CONCLUSIONS: Patients diagnosed as LSS with RA have amounts of HBL or mHBL after PLIF. HBL or mHBL is not associated with RA activity, which may not increase in RA patients compared with common ones. Taking DMARDs may reduce postoperative DBL. The fact that mHBL is larger than HBL provides an all-round basis for measuring factual HBL.

11.
J Surg Oncol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617593

RESUMO

BACKGROUND: Patients with distal cholangiocarcinoma (DCC) are prone to relapse even after radical pancreaticoduodenectomy. In this study, we sought to create an online nomogram calculator to accurately predict the recurrence risk of DCC. METHODS: A total of 184 patients were included. Multivariate Cox regression analysis was used to identify independent prognosis factors for recurrence-free survival and overall survival. A nomogram was constructed according to the prognostic factors in the training cohort and then tested in the validation cohort. RESULTS: Multivariate Cox analysis showed preoperative carbohydrate antigen 19-9 (p < 0.001), maximum tumor size (p = 0.076), perineural invasion (p = 0.044), and N stage (p = 0.076) were independent prognostic factors for DCC relapse. We then constructed a nomogram with these four factors. The consistency index (C-index) of the nomogram in the training and validation cohorts were 0.703 and 0.665, respectively. Time-dependent receiver operating characteristic and decision curve analyses revealed that the nomogram provided higher diagnostic power and net benefit compared with other staging systems. CONCLUSION: In this study, we developed an online nomogram calculator that can accurately predict the recurrence risk of DCC and identify patients with a high risk of recurrence in a simple and convenient manner.

12.
J Asian Nat Prod Res ; : 1-14, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622714

RESUMO

The endophytic fungus Diaporthe sp. is known to contain many secondary metabolites, but fatty acid derivatives have rarely been found. In this study, four new fatty acid derivatives (1-4), together with four known compounds (5-8), were isolated from Diaporthe sp., which was obtained from the stem of Ligularia fischeri. The absolute configurations of the new compounds 1-4 were deduced based on spectroscopic technique and J-based coupling constant analysis. Moreover, compound 1 exhibited cytotoxic activities against HCT-8 and MCF-7 cancer cells, and compounds 3 and 4 showed modest selectivity for HCT-8 cells by MTT assay.

13.
Medicine (Baltimore) ; 100(39): e26851, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596108

RESUMO

ABSTRACT: The incidence of degenerative spinal deformity (DSD) is increasing with the age while the effect of DSD on the abdominal cavity parameters is unclear.To identify the characteristics of abdominal change in DSD and to explore the correlation between the abdominal cavity volume (ACV) and various types of DSD.The retrospective study included 95 patients with DSD and 100 subjects without deformity as control group. The Cobb angle, thoracic kyphosis angle, thoracolumbar kyphosis (TLK) angle, and lumbar kyphosis angle were obtained through full-length X-ray. The ACV was calculated by measuring the longitudinal, transversal, and coronal diameters of the abdominal cavity on magnetic resonance imaging (MRI). The rotation of the diaphragm (DR) were measured in the sagittal plane. DSD ones were divided into degenerative lumbar scoliosis (DLS group), degenerative kyphosis (DK group), and degenerative lumbar scoliokyphosis (DKS group).Compared to control group, ACV of the DLS and DKS group was smaller. The distance between the xiphoid process and spine in DLS group was shorter and DR in DK group and DKS group was smaller. The inter-group analysis showed ACV and the shortest distance between xiphoid process and spine in DLS and DKS group were significantly lower than those in DK group. The degree of DR in DK group and DKS group was higher than that in the DLS group. Multiple linear regression analysis showed Cobb angle and weight were influencing factors of ACV with ACV = 0.67 × weight - 0.19 × Cobb angle + 2231.8. The DR was affected by TLK with DR = 25.82 - 0.42 × TLK.DLS can cause the decrease of ACV. DK will not cause changes of ACV but is related to the degree of kyphosis. DKS will impact both ACV and DR.


Assuntos
Cavidade Abdominal/patologia , Curvaturas da Coluna Vertebral/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Retrospectivos
14.
Artigo em Inglês | MEDLINE | ID: mdl-34676993

RESUMO

BACKGROUND: Distal cholangiocarcinoma (DCC) is a malignancy associated with a short survival time. In this study, we aimed to create an online nomogram calculator to predict early recurrence and long-term survival in patients with DCC after pancreaticoduodenectomy. METHODS: A total of 486 patients with DCC were included. An online nomogram calculator was developed and validated in training, internal validation and external validation cohorts, respectively. RESULTS: Of the 486 patients who met the inclusion criteria, we allocated 240, 120, and 126 patients to the training, internal validation, and external validation cohorts, respectively. Multivariable analysis showed that preoperative CA19-9, maximum tumor diameter, perineural invasion, and tumor differentiation were significant risk factors for early recurrence in patients with DCC. Incorporating these four factors, the nomogram achieved good AUC values of 0.788, 0.771, and 0.723 for predicting early recurrence in the training, internal validation, and external validation cohorts, respectively. Notably, this nomogram also had good power to predict overall survival. The discrimination ability of the nomogram was evaluated by dividing the predicted probabilities of early recurrence and survival into two risk groups in the training cohort (low risk ≤ 132; high risk > 132; P < .001). Time-dependent ROC and decision curve analysis further revealed that the nomogram provided higher diagnostic capacity and superior net benefit compared to other staging systems. CONCLUSION: This study developed and validated a web-based nomogram calculator that was capable of predicting early recurrence and long-term prognosis in patients with DCC after pancreaticoduodenectomy with high degrees of stability and accuracy.

15.
Proc Natl Acad Sci U S A ; 118(43)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34663725

RESUMO

Early identification of atypical infant movement behaviors consistent with underlying neuromotor pathologies can expedite timely enrollment in therapeutic interventions that exploit inherent neuroplasticity to promote recovery. Traditional neuromotor assessments rely on qualitative evaluations performed by specially trained personnel, mostly available in tertiary medical centers or specialized facilities. Such approaches are high in cost, require geographic proximity to advanced healthcare resources, and yield mostly qualitative insight. This paper introduces a simple, low-cost alternative in the form of a technology customized for quantitatively capturing continuous, full-body kinematics of infants during free living conditions at home or in clinical settings while simultaneously recording essential vital signs data. The system consists of a wireless network of small, flexible inertial sensors placed at strategic locations across the body and operated in a wide-bandwidth and time-synchronized fashion. The data serve as the basis for reconstructing three-dimensional motions in avatar form without the need for video recordings and associated privacy concerns, for remote visual assessments by experts. These quantitative measurements can also be presented in graphical format and analyzed with machine-learning techniques, with potential to automate and systematize traditional motor assessments. Clinical implementations with infants at low and at elevated risks for atypical neuromotor development illustrates application of this system in quantitative and semiquantitative assessments of patterns of gross motor skills, along with body temperature, heart rate, and respiratory rate, from long-term and follow-up measurements over a 3-mo period following birth. The engineering aspects are compatible for scaled deployment, with the potential to improve health outcomes for children worldwide via early, pragmatic detection methods.

16.
Bioengineered ; 12(1): 6045-6056, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34482800

RESUMO

Allergic rhinitis (AR) is a symptomatic allergic disease that leads to severe inflammation. Astragaloside IV (AS-IV) is a primary active component of Astragalus membranaceus and exerts immune-regulation and anti-inflammatory effects. However, the pharmacological effect of AS-IV in the nasal epithelial cells (NECs) has not been reported. The present study aimed to assess the effect of AS-IV on inflammatory cytokines and mucin 5 subtype AC (MUC5AC) overproduction in histamine (His)-stimulated NECs and its underlying mechanism. NECs were stimulated with or without His for 24 h in the absence or presence of AS-IV. The levels of inflammatory cytokines including IL-6, IL-8, MCP-1, IL-1ß, granulocyte-macrophage colony-stimulating factor (GM-CSF), eotaxin, and MUC5AC were assayed. Our findings indicated that AS-IV inhibited His-evoked release and expression of inflammatory cytokines and MUC5AC in NECs. RNA-seq analyses indicated the significant changes in expression levels involved in inflammation genes upon treatment of His-induced NECs with AS-IV. Our findings indicated that AS-IV inhibited His-evoked inflammatory cytokines secretion and MUC5AC overproduction in NECs, which were partly mediated by regulation of inflammation-related genes. Therefore, our findings provided a scientific basis for the development of AS-IV as an effective agent for clinical therapeutic strategy in the treatment of AR.

17.
Adv Mater ; 33(44): e2103974, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510572

RESUMO

Continuous monitoring of vital signs is an essential aspect of operations in neonatal and pediatric intensive care units (NICUs and PICUs), of particular importance to extremely premature and/or critically ill patients. Current approaches require multiple sensors taped to the skin and connected via hard-wired interfaces to external data acquisition electronics. The adhesives can cause iatrogenic injuries to fragile, underdeveloped skin, and the wires can complicate even the most routine tasks in patient care. Here, materials strategies and design concepts are introduced that significantly improve these platforms through the use of optimized materials, open (i.e., "holey") layouts and precurved designs. These schemes 1) reduce the stresses at the skin interface, 2) facilitate release of interfacial moisture from transepidermal water loss, 3) allow visual inspection of the skin for rashes or other forms of irritation, 4) enable triggered reduction of adhesion to reduce the probability for injuries that can result from device removal. A combination of systematic benchtop testing and computational modeling identifies the essential mechanisms and key considerations. Demonstrations on adult volunteers and on a neonate in an operating NICUs illustrate a broad range of capabilities in continuous, clinical-grade monitoring of conventional vital signs, and unconventional indicators of health status.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34518900

RESUMO

PURPOSE: The evidence regarding programmed cell death 1 (PD-1) inhibitors on pancreatic ductal adenocarcinoma (PDAC) with metastases remains controversial. This study aimed to assess the efficacy and safety of Nab-paclitaxel plus S1 (NPS) with or without Sintilimab, a PD-1 inhibitor, in patients with PDAC with only hepatic metastases (mPDAC). METHODS: Untreated mPDAC patients who received NPS with (the combination group) or without Sintilimab (the NPS group) were retrospectively studied. Surgery was considered when the pancreatic tumor became resectable or borderline resectable on radiological examinations, and with complete metabolic response of liver metastases. RESULTS: Between October 2017 and February 2020, 32 patients were in the combination group and 34 patients in the NPS group. Successful salvage resection was achieved in 17 (25.8%) patients after tumor-downstaging (combination 12 vs. NPS 5, P = 0.03). The median overall survival (OS) was 16.8 months in the combination group and 10.0 months in the NPS group (P = 0.002). Remarkable OS benefit was observed in patients with decline in CA19-9 of ≥ 50% (16.0 vs. 6.5, P = 0.003), reduction in 18F-fluorodeoxyglucose uptake of primary tumor of ≥ 50% (16.5 vs. 10.0, P < 0. 001) and after salvage resection (20.1 vs. 11.0, P < 0. 001). No significant difference in Grade 3 or higher adverse events were seen between the two groups (40.6% vs. 32.4%, P = 0.49). CONCLUSIONS: Despite the inherent biases of this retrospective study, the addition of Sintilimab significantly improved salvage resection rates and OS compared with the NPS regimen and had a favorable safety profile in treatment naïve mPDAC patients.

19.
Chem Soc Rev ; 50(21): 11766-11784, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570124

RESUMO

In situ monitoring of the location and transportation of bioactive molecules is essential for deciphering diverse biological events in the field of biomedicine. In addition, obtaining the in situ information of lesions will provide a clear perspective for surgeons to perform precise resection in clinical surgery. Notably, delivering drugs or operating photodynamic therapy/photothermal therapy in situ by labeling the lesion regions of interest can improve treatment and reduce side effects in vivo. In various advanced imaging and therapy modalities, optical theranostic agents based on organic small molecules can be conveniently modified as needed and can be easily internalized into cells/lesions in a non-invasive manner, which are prerequisites for in situ bioimaging and precision treatment. In this tutorial review, we first summarize the in situ molecular immobilization strategies to retain small-molecule agents inside cells/lesions to prevent their diffusion in living organisms. Emphasis will be focused on introducing the application of these strategies for in situ imaging of biomolecules and precision treatment, particularly pertaining to why targeting therapy in situ is required.

20.
Front Aging Neurosci ; 13: 660621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434100

RESUMO

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a common disease in elderly adults. Patients with iNPH are generally characterized by progressive gait impairment, cognitive deficits, and urinary urgency and/or incontinence. A number of radiographic studies have shown that iNPH patients have enlarged ventricles and altered brain morphology; however, few studies have focused on the relationships between altered brain structure and gait dysfunction due to iNPH. Thus, this study aimed to evaluate the abnormalities of white matter (WM) correlated with gait impairment in iNPH patients and to gain a better understanding of its underlying pathology. Methods: Fifteen iNPH patients (five women, 10 men) were enrolled in this study, and each patient's demographic and gait indices were collected. First, we performed a correlation analysis between the demographic and gait indices. Then, all gait indices were grouped according to the number of WM hyperintensities (WMH) among each WM tract (JHU WM tractography atlas), to perform comparative analysis. Results: Considering sex and illness duration as covariates, correlation analysis showed a significantly negative correlation between step length (r = -0.80, p = 0.001), pace (r = -0.84, p = 2.96e-4), and age. After removing the effects of age, sex, and illness duration, correlation analysis showed negative correlation between step length (r = -0.73, p = 0.007), pace (r = -0.74, p = 0.005), and clinical-grade score and positive correlation between 3-m round trip time (r = 0.66, p = 0.021), rising time (r = 0.76, p = 0.004), and clinical-grade score. Based on WMH of each white matter tract, gait indices showed significant differences (p < 0.05/48, corrected by Bonferroni) between fewer WMH patients and more WMH in the middle cerebellar peduncle, left medial lemniscus, left posterior limb of the internal capsule (IC), and right posterior limb of the IC. Conclusions: Our results indicated that iNPH patients exhibited gait-related WM abnormalities located in motor and sensory pathways around the ventricle, which is beneficial to understand the underlying pathology of iNPH.

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