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1.
Int J Ophthalmol ; 17(6): 1110-1119, 2024.
Article in English | MEDLINE | ID: mdl-38895674

ABSTRACT

AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

2.
Int J Low Extrem Wounds ; : 15347346241245087, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38572515

ABSTRACT

OBJECTIVE: The objective of this study is to assess the efficacy of decompression nursing based on biomechanical principles in managing recurrent diabetic plantar ulcers. METHODS: Sixty-seven patients experiencing recurrent diabetic plantar ulcers who sought medical attention at Huadong Hospital Affiliated to Fudan University between January 2021 and December 2022 were selected as participants for this study. The participants underwent biomechanics-based decompression nursing. We compared pre-intervention and post-intervention data to assess the differences in relevant observational indexes. RESULTS: Post-intervention, patients showed significant improvements in foot comfort scores and adherence to pressure reduction behavior compared with their pre-intervention status, with statistical significance (P < 0.05). The intervention was effective in 41 cases (61.19%), with 18 cases (26.87%) showing improvement and 8 cases (11.94%) deemed ineffective, culminating in an overall efficacy rate of 88.06%. All 67 patients achieved complete ulcer healing within an average duration of 58.63 ± 18.13 days, without any recorded recurrences. CONCLUSION: Biomechanics-based decompression nursing demonstrates effective facilitation of wound healing, yielding expeditious recovery, enhanced comfort, and a reduced incidence of recurrence.

3.
EBioMedicine ; 103: 105094, 2024 May.
Article in English | MEDLINE | ID: mdl-38579366

ABSTRACT

BACKGROUND: Sleep and circadian rhythm disruptions are common in patients with mood disorders. The intricate relationship between these disruptions and mood has been investigated, but their causal dynamics remain unknown. METHODS: We analysed data from 139 patients (76 female, mean age = 23.5 ± 3.64 years) with mood disorders who participated in a prospective observational study in South Korea. The patients wore wearable devices to monitor sleep and engaged in smartphone-delivered ecological momentary assessment of mood symptoms. Using a mathematical model, we estimated their daily circadian phase based on sleep data. Subsequently, we obtained daily time series for sleep/circadian phase estimates and mood symptoms spanning >40,000 days. We analysed the causal relationship between the time series using transfer entropy, a non-linear causal inference method. FINDINGS: The transfer entropy analysis suggested causality from circadian phase disturbance to mood symptoms in both patients with MDD (n = 45) and BD type I (n = 35), as 66.7% and 85.7% of the patients with a large dataset (>600 days) showed causality, but not in patients with BD type II (n = 59). Surprisingly, no causal relationship was suggested between sleep phase disturbances and mood symptoms. INTERPRETATION: Our findings suggest that in patients with mood disorders, circadian phase disturbances directly precede mood symptoms. This underscores the potential of targeting circadian rhythms in digital medicine, such as sleep or light exposure interventions, to restore circadian phase and thereby manage mood disorders effectively. FUNDING: Institute for Basic Science, the Human Frontiers Science Program Organization, the National Research Foundation of Korea, and the Ministry of Health & Welfare of South Korea.


Subject(s)
Affect , Bipolar Disorder , Circadian Rhythm , Depressive Disorder, Major , Sleep , Wearable Electronic Devices , Humans , Female , Male , Adult , Bipolar Disorder/physiopathology , Bipolar Disorder/psychology , Sleep/physiology , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/psychology , Young Adult , Republic of Korea , Prospective Studies , Smartphone
4.
Phys Rev Lett ; 132(7): 078402, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38427894

ABSTRACT

Genetic oscillations are generated by delayed transcriptional negative feedback loops, wherein repressor proteins inhibit their own synthesis after a temporal production delay. This delay is distributed because it arises from a sequence of noisy processes, including transcription, translocation, translation, and folding. Because the delay determines repression timing and, therefore, oscillation period, it has been commonly believed that delay noise weakens oscillatory dynamics. Here, we demonstrate that noisy delay can surprisingly denoise genetic oscillators. Specifically, moderate delay noise improves the signal-to-noise ratio and sharpens oscillation peaks, all without impacting period and amplitude. We show that this denoising phenomenon occurs in a variety of well-studied genetic oscillators, and we use queueing theory to uncover the universal mechanisms that produce it.

5.
Waste Manag ; 176: 1-10, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38246072

ABSTRACT

With continuous advancements in the zero-waste strategy in China, transportation of fresh municipal solid waste to landfills has ceased in most first-tier cities. Consequently, the production of landfill gas has sharply declined because the supply of organic matter has decreased, rendering power generation facilities idle. However, by incorporating liquefied kitchen and food waste (LKFW), sustainable methane production can be achieved while consuming organic wastewater. In this study, LKFW and water (as a control group) were periodically injected into high and low organic wastes, respectively. The biochemical characteristics of the resulting gas and leachate were analyzed. LKFW used in this research generated 19.5-37.6 L of methane per liter in the post-methane production phase, highlighting the effectiveness of LKFW injection in enhancing the methane-producing capacity of the system. The release of H2S was prominent during both the rapid and post-methane production phases, whereas that of NH3 was prominent in the post-methane production phase. As injection continued, the concentrations of chemical oxygen demand, 5-d biological oxygen demand, total organic carbon, ammonia nitrogen, total nitrogen, and oil in the output leachate decreased and eventually reached levels comparable to those in the water injection cases. After nine rounds of injections, the biologically degradable matter of the two LKFW-injected wastes decreased by 8.2 % and 15.1 %, respectively. This study sheds light on determining the organic load, controlling odor, and assessing the biochemical characteristics of leachate during LKFW injection.


Subject(s)
Refuse Disposal , Water Pollutants, Chemical , Solid Waste , Refuse Disposal/methods , Food Loss and Waste , Food , Bioreactors , Water Pollutants, Chemical/analysis , Waste Disposal Facilities , Methane/analysis , Water , Nitrogen
6.
Sleep ; 47(1)2024 01 11.
Article in English | MEDLINE | ID: mdl-37819273

ABSTRACT

Sleep is a critical component of health and well-being but collecting and analyzing accurate longitudinal sleep data can be challenging, especially outside of laboratory settings. We propose a simple neural network model titled SOMNI (Sleep data restOration using Machine learning and Non-negative matrix factorIzation [NMF]) for imputing missing rest-activity data from actigraphy, which can enable clinicians to better handle missing data and monitor sleep-wake cycles of individuals with highly irregular sleep-wake patterns. The model consists of two hidden layers and uses NMF to capture hidden longitudinal sleep-wake patterns of individuals with disturbed sleep-wake cycles. Based on this, we develop two approaches: the individual approach imputes missing data based on the data from only one participant, while the global approach imputes missing data based on the data across multiple participants. Our models are tested with shift and non-shift workers' data from three independent hospitals. Both approaches can accurately impute missing data up to 24 hours of long dataset (>50 days) even for shift workers with extremely irregular sleep-wake patterns (AUC > 0.86). On the other hand, for short dataset (~15 days), only the global model is accurate (AUC > 0.77). Our approach can be used to help clinicians monitor sleep-wake cycles of patients with sleep disorders outside of laboratory settings without relying on sleep diaries, ultimately improving sleep health outcomes.


Subject(s)
Sleep Disorders, Circadian Rhythm , Wearable Electronic Devices , Humans , Sleep , Neural Networks, Computer , Algorithms , Rest , Actigraphy
7.
Am J Respir Cell Mol Biol ; 70(3): 193-202, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38029303

ABSTRACT

The high mortality rate in patients with chronic obstructive pulmonary disease (COPD) may be due to pulmonary hypertension (PH). These diseases are highly associated with cigarette smoke and its key component nicotine. Here, we created a novel animal model of PH using coexposure to nicotine (or cigarette smoke) and hypoxia. This heretofore unreported model showed significant early-onset pulmonary vasoremodeling and PH. Using newly generated mice with complementary smooth muscle-specific Rieske iron-sulfur protein (RISP) gene knockout and overexpression, we demonstrate that RISP is critically involved in promoting pulmonary vasoremodeling and PH, which are implemented by oxidative ataxia telangiectasia-mutated-mediated DNA damage and NF-κB-dependent inflammation in a reciprocal positive mechanism. Together, our findings establish for the first time an animal model of hypoxia-induced early-onset PH in which mitochondrial RISP-dependent DNA damage and NF-κB inflammation play critical roles in vasoremodeling. Specific therapeutic targets for RISP and related oxidative stress-associated signaling pathways may create unique and effective treatments for PH, chronic obstructive pulmonary disease, and their complications.


Subject(s)
Electron Transport Complex III , Hypertension, Pulmonary , Pulmonary Disease, Chronic Obstructive , Humans , Animals , Mice , Nicotine , NF-kappa B , Hypoxia/complications , DNA, Mitochondrial , Inflammation
8.
Environ Geochem Health ; 46(1): 1, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38063932

ABSTRACT

The municipal solid waste (MSW) landfill in Hangzhou, China utilized zeolite and activated carbon (AC) as permeable reactive barrier (PRB) fill materials to remediate groundwater contaminated with MSW leachates containing ammonium, chemical oxygen demand (COD), and heavy metals. The spectral induced polarization (SIP) technique was chosen for monitoring the PRB because of its sensitivity to pore fluid chemistry and mineral-fluid interface composition. During the experiment, authentic groundwater collected from the landfill site was used to permeate two columns filled with zeolite and AC, and the SIP responses were measured at the inlet and outlet over a frequency range of 0.01-1000 Hz. The results showed that zeolite had a higher adsorption capacity for COD (7.08 mg/g) and ammonium (9.15 mg/g) compared to AC (COD: 2.75 mg/g, ammonium: 1.68 mg/g). Cation exchange was found to be the mechanism of ammonium adsorption for both zeolite and AC, while FTIR results indicated that π-complexation, π-π interaction, and electrostatic attraction were the main mechanisms of COD adsorption. The Cole-Cole model was used to fit the SIP responses and determine the relaxation time (τ) and normalized chargeability (mn). The calculated characteristic diameters of zeolite and AC based on the Schwarz equation and relaxation time (τ) matched the pore sizes observed from SEM and MIP, providing valuable information on contaminant distribution. The mn of zeolite was positively linear with adsorbed ammonium (R2 = 0.9074) and COD (R2 = 0.8877), while the mn of AC was negatively linear with adsorbed ammonium (R2 = 0.8192) and COD (R2 = 0.7916), suggesting that mn could serve as a surrogate for contaminant saturation. The laboratory-based real-time non-invasive SIP results showed good performance in monitoring saturation and provide a strong foundation for future field PRB monitoring.


Subject(s)
Ammonium Compounds , Groundwater , Water Pollutants, Chemical , Zeolites , Solid Waste , Water Pollutants, Chemical/analysis , Zeolites/chemistry , Charcoal , Groundwater/chemistry
9.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5122-5130, 2023 Oct.
Article in Chinese | MEDLINE | ID: mdl-38114102

ABSTRACT

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.


Subject(s)
Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/chemically induced , Quality of Life , Sleep , Hypnotics and Sedatives/therapeutic use , Hypnotics and Sedatives/pharmacology , Antidepressive Agents/therapeutic use , Antidepressive Agents/pharmacology
10.
Sci Rep ; 13(1): 17846, 2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37857808

ABSTRACT

Demand is increasing for photovoltaics (PVs) as a result of the development of the Internet of Things and edge computing technologies. As the lighting environment is different for the applications, thus, PVs must be adjustable to various light environments in which systems are installed. PVs should therefore be capable of easily changing their morphology without damaging the cells. To address this problem, in this work, a three-dimensional (3D) structure that increases power output under omnidirectional light was applied to a crystalline silicon solar cell array using a block-type method. The resultant block-type 3D indoor PV could operate a Bluetooth low-energy module in conjunction with a power management integrated circuit when the illuminance was 532 lx and 1620 lx and each PV installation area was 129.9cm2 and 32.48 cm2 respectively.

11.
BMJ Open Ophthalmol ; 8(Suppl 2): A15, 2023 08.
Article in English | MEDLINE | ID: mdl-37604547

ABSTRACT

PURPOSE: The aim of our presentation is to introduce future eye bank product - corneal stromal lenticule from living donors, which can be used for allotransplantation. METHODS: ReLEx (refractive lenticule extraction) SMILE (small incision lenticule extraction) is a common approach in laser eye surgery. It is minimally invasive and flap-free procedure. During this procedure part of corneal stroma (lenticule) is created by femtosecond laser and consequently removed through small incision. The lenticule is basically waste material of the ReLEx SMILE procedure. In the International Eye Bank of Prague, we decided to establish new protocol for lenticule withdrawal, storage and release for transplantation. RESULTS: All donors signed an informed consent, and their serum was tested for the presence of infectious diseases. After ReLEx SMILE procedure the lenticule was stored in container with cryopreservation solution and frozen in the eye bank using the same protocol for frozen amniotic membrane. After 6 months in -80°C tissues were defrosted and examined histologically, using conventional light histology staining and electron microscopy. CONCLUSION: We believe, that lenticule from living donor is a safe and effective tissue, that can be used for many indications and in particular situations represents good alternative to whole donor cornea and amniotic membrane.


Subject(s)
Corneal Stroma , Eye Banks , Humans , Corneal Stroma/surgery , Smiling , Cornea , Living Donors
12.
Sleep ; 46(9)2023 09 08.
Article in English | MEDLINE | ID: mdl-37422720

ABSTRACT

The prevalence of artificial light exposure has enabled us to be active any time of the day or night, leading to the need for high alertness outside of traditional daytime hours. To address this need, we developed a personalized sleep intervention framework that analyzes real-world sleep-wake patterns obtained from wearable devices to maximize alertness during specific target periods. Our framework utilizes a mathematical model that tracks the dynamic sleep pressure and circadian rhythm based on the user's sleep history. In this way, the model accurately predicts real-time alertness, even for shift workers with complex sleep and work schedules (N = 71, t = 13~21 days). This allowed us to discover a new sleep-wake pattern called the adaptive circadian split sleep, which incorporates a main sleep period and a late nap to enable high alertness during both work and non-work periods of shift workers. We further developed a mobile application that integrates this framework to recommend practical, personalized sleep schedules for individual users to maximize their alertness during a targeted activity time based on their desired sleep onset and available sleep duration. This can reduce the risk of errors for those who require high alertness during nontraditional activity times and improve the health and quality of life for those leading shift work-like lifestyles.


Subject(s)
Wakefulness , Wearable Electronic Devices , Humans , Quality of Life , Work Schedule Tolerance , Sleep , Circadian Rhythm , Models, Theoretical
13.
iScience ; 26(6): 106745, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37378326

ABSTRACT

The urban application of photovoltaics is necessary to achieve carbon-free electricity production. However, the serial connections within modules cause problems under partial shading conditions, which is inevitable in urban applications. Therefore, a partial shading-tolerance photovoltaic module is needed. This research introduces the small-area-high-voltage (SAHiV) module with rectangle and triangle shapes for high partial shading tolerance and compares its performance with conventional and shingled modules. We tested it with discrete and continuous shading shape groups to represent unpredictable shading by simulations using LTspice with Monte Carlo simulation combined with latin hypercube sampling that were validated by comparison with experimental results. The SAHiV triangle module exhibited the best partial shading tolerance under most scenarios. Both types of SAHiV modules (rectangular and triangular) were robust against all types of shading patterns and angles, as indicated by their stable shading-tolerance values. These modules are thus suitable for use in urban areas.

14.
Nutr Res ; 116: 12-23, 2023 08.
Article in English | MEDLINE | ID: mdl-37320947

ABSTRACT

Protein restriction (PR) leads to bone marrow hypoplasia with changes in stromal cellularity components of the extracellular matrix in hematopoietic stem cells (HSCs). However, the underlying signaling mechanisms are poorly understood. We hypothesize that PR impairs the HSC mitogen-activated protein kinase (MAPK) signaling pathway response activation. Our aim is to evaluate the activation of MAPK and interleukin-3 (IL-3) proteins in HSC to explain PR-induced bone marrow hypoplasia, which causes altered proliferation and differentiation. C57BL/6 male mice were subjected to a low-protein diet (2% protein) or normoproteic (12% protein). PKC, PLCγ2, CaMKII, AKT, STAT3/5, ERK1/2, JNK, and p38d phosphorylation were evaluated by flow cytometry, and GATA1/2, PU.1, C/EBPα, NF-E2, and Ikz-3 genes (mRNAs) assessed by quantitative real-time-polymerase chain reaction. Pathway proteins, such as PLCγ2, JAK2, STAT3/5, PKC, and RAS do not respond to the IL-3 stimulus in PR, leading to lower activation of ERK1/2 and Ca2+ signaling pathways, consequently lowering the production of hematopoietic transcription factors. Colony forming units granulocyte-macrophage and colony forming units macrophage formation are impaired in PR even after being stimulated with IL-3. Long-term hematopoietic stem cells, short-term hematopoietic stem cells, granulocyte myeloid progenitor, and megakaryocyte-erythroid progenitor cells were significantly reduced in PR animals. This study shows for the first time that activation of MAPK pathway key proteins in HSCs is impaired in cases of PR. Several pathway proteins, such as PLCγ2, JAK2, STAT3, PKC, and RAS do not respond to IL-3 stimulation, leading to lower activation of extracellular signal-regulated protein kinase 1/2 and consequently lower production of hematopoietic transcription factors GATA1/2, PU.1, C/EBPa, NF-E2, and Ikz3. These changes result in a reduction in colony-forming units, proliferation, and differentiation, leading to hypocellularity.


Subject(s)
Diet, Protein-Restricted , Hematopoietic Stem Cells , Mitogen-Activated Protein Kinases , Animals , Male , Mice , Interleukin-3 , Mice, Inbred C57BL , Phospholipase C gamma , Signal Transduction , Transcription Factors
15.
Genes (Basel) ; 14(6)2023 05 27.
Article in English | MEDLINE | ID: mdl-37372352

ABSTRACT

Trichopoda pennipes is a tachinid parasitoid of several significant heteropteran agricultural pests, including the southern green stink bug, Nezara viridula, and leaf-footed bug, Leptoglossus phyllopus. To be used successfully as a biological control agent, the fly must selectively parasitize the target host species. Differences in the host preference of T. pennipes were assessed by assembling the nuclear and mitochondrial genomes of 38 flies reared from field-collected N. viridula and L. phyllopus. High-quality de novo draft genomes of T. pennipes were assembled using long-read sequencing. The assembly totaled 672 MB distributed among 561 contigs, having an N50 of 11.9 MB and a GC of 31.7%, with the longest contig at 28 MB. The genome was assessed for completeness using BUSCO in the Insecta dataset, resulting in a score of 99.4%, and 97.4% of the genes were single copy-loci. The mitochondrial genomes of the 38 T. pennipes flies were sequenced and compared to identify possible host-determined sibling species. The assembled circular genomes ranged from 15,345 bp to 16,390 bp and encode 22 tRNAs, two rRNAs, and 13 protein-coding genes (PCGs). There were no differences in the architecture of these genomes. Phylogenetic analyses using sequence information from 13 PCGs and the two rRNAs individually or as a combined dataset resolved the parasitoids into two distinct lineages: T. pennipes that parasitized both N. viridula and L. phyllopus, and others that parasitized only L. phyllopus.


Subject(s)
Diptera , Genome, Mitochondrial , Heteroptera , Animals , Genome, Mitochondrial/genetics , Phylogeny , Agriculture
16.
iScience ; 26(5): 106603, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37128611

ABSTRACT

G proteins are major signaling partners for G protein-coupled receptors (GPCRs). Although stepwise structural changes during GPCR-G protein complex formation and guanosine diphosphate (GDP) release have been reported, no information is available with regard to guanosine triphosphate (GTP) binding. Here, we used a novel Bayesian integrative modeling framework that combines data from hydrogen-deuterium exchange mass spectrometry, tryptophan-induced fluorescence quenching, and metadynamics simulations to derive a kinetic model and atomic-level characterization of stepwise conformational changes incurred by the ß2-adrenergic receptor (ß2AR)-Gs complex after GDP release and GTP binding. Our data suggest rapid GTP binding and GTP-induced dissociation of Gαs from ß2AR and Gßγ, as opposed to a slow closing of the Gαs α-helical domain (AHD). Yeast-two-hybrid screening using Gαs AHD as bait identified melanoma-associated antigen D2 (MAGE D2) as a novel AHD-binding protein, which was also shown to accelerate the GTP-induced closing of the Gαs AHD.

17.
Front Oncol ; 13: 1003977, 2023.
Article in English | MEDLINE | ID: mdl-36816974

ABSTRACT

Background: Although the overall global incidence of gastric cancer has been declining, the number of new cases in people under the age of 50 is increasing, which is related to metastasis, late pathological stages, and poor prognosis. There is a scarcity of large-scale studies to evaluate and predict distant metastasis in patients with early-onset gastric cancer. Methods: From January 2010 to December 2019, data on early-onset GC patients undergoing surgery were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the independent risk factors for distant metastasis in patients with early-onset gastric cancer. Based on these risk factors, we developed a nomogram to predict distant metastasis. The model underwent internal validation on the test set and external validation on 205 patients from the First Affiliated Hospital of Sun Yat-sen University and the seventh Affiliated Hospital of Sun Yat-sen University. The novel nomogram model was then evaluated using the receiver operating characteristic (ROC) curve, calibration, the area under the curve (AUC), and decision curve analysis (DCA). The training set nomogram score was used to classify the different risk clusters of distant metastasis. Results: Our study enrolled 2217 patients after establishing the inclusion and exclusion criteria, with 1873 having no distant metastasis and 344 having distant metastasis. The tumor size, total lymph nodes, whether or not receiving radiotherapy and chemotherapy, T stage, and N stage were significant predictors of advanced distant metastasis (p < 0.05). The AUC of the ROC analysis demonstrated our model's high accuracy. Simultaneously, the prediction model shows high stability and clinical practicability in the calibration curve and DCA analysis. Conclusions: We developed an innovative nomogram containing clinical and pathological characteristics to predict distant metastasis in patients younger than 50 years old with gastric cancer. The tool can alert clinicians about distant metastasis and help them develop more effective clinical treatment plans.

18.
J Gen Physiol ; 155(3)2023 03 06.
Article in English | MEDLINE | ID: mdl-36625865

ABSTRACT

Pulmonary hypertension (PH) is a devastating disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular failure and death. A major cellular response in this disease is the contraction of smooth muscle cells (SMCs) of the pulmonary vasculature. Cell contraction is determined by the increase in intracellular Ca2+ concentration ([Ca2+]i), which is generated and regulated by various ion channels. Several studies by us and others have shown that ryanodine receptor 2 (RyR2), a Ca2+-releasing channel in the sarcoplasmic reticulum (SR), is an essential ion channel for the control of [Ca2+]i in pulmonary artery SMCs (PASMCs), thereby mediating the sustained vasoconstriction seen in PH. FK506-binding protein 12.6 (FKBP12.6) strongly associates with RyR2 to stabilize its functional activity. FKBP12.6 can be dissociated from RyR2 by a hypoxic stimulus to increase channel function and Ca2+ release, leading to pulmonary vasoconstriction and PH. More specifically, dissociation of the RyR2-FKBP12.6 complex is a consequence of increased mitochondrial ROS generation mediated by the Rieske iron-sulfur protein (RISP) at the mitochondrial complex III after hypoxia. Overall, RyR2/FKBP12.6 dissociation and the corresponding signaling pathway may be an important factor in the development of PH. Novel drugs and biologics targeting RyR2, FKBP12.6, and related molecules may become unique effective therapeutics for PH.


Subject(s)
Hypertension, Pulmonary , Humans , Hypertension, Pulmonary/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism , Calcium/metabolism , Sarcoplasmic Reticulum/metabolism , Tacrolimus Binding Proteins/metabolism
19.
Clin Pharmacol Ther ; 113(5): 1048-1057, 2023 05.
Article in English | MEDLINE | ID: mdl-36519932

ABSTRACT

The US Food and Drug Administration (FDA) guidance has recommended several model-based predictions to determine potential drug-drug interactions (DDIs) mediated by cytochrome P450 (CYP) induction. In particular, the ratio of substrate area under the plasma concentration-time curve (AUCR) under and not under the effect of inducers is predicted by the Michaelis-Menten (MM) model, where the MM constant ( K m ) of a drug is implicitly assumed to be sufficiently higher than the concentration of CYP enzymes that metabolize the drug ( E T ) in both the liver and small intestine. Furthermore, the fraction absorbed from gut lumen ( F a ) is also assumed to be one because F a is usually unknown. Here, we found that such assumptions lead to serious errors in predictions of AUCR. To resolve this, we propose a new framework to predict AUCR. Specifically, F a was re-estimated from experimental permeability values rather than assuming it to be one. Importantly, we used the total quasi-steady-state approximation to derive a new equation, which is valid regardless of the relationship between K m and E T , unlike the MM model. Thus, our framework becomes much more accurate than the original FDA equation, especially for drugs with high affinities, such as midazolam or strong inducers, such as rifampicin, so that the ratio between K m and E T becomes low (i.e., the MM model is invalid). Our work greatly improves the prediction of clinical DDIs, which is critical to preventing drug toxicity and failure.


Subject(s)
Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System , Humans , Drug Interactions , Pharmaceutical Preparations , Cytochrome P-450 Enzyme System/metabolism , Rifampin/pharmacology , Midazolam
20.
J Glaucoma ; 32(3): 227-235, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36256952

ABSTRACT

PRCIS: Deep sclerectomy (DS) with the Esnoper Clip drainage implant in patients with uncontrolled primary open angle glaucoma (POAG) achieved a complete success rate of 87.2% at the 1-year follow-up. PURPOSE: To investigate the efficacy and safety of DS followed by Esnoper Clip implantation in patients with uncontrolled POAG. MATERIALS AND METHODS: In a prospective, consecutive, interventional study, we investigated 39 eyes of 35 patients with uncontrolled POAG who underwent DS with Esnoper Clip implantation. Complete ophthalmologic examinations including corrected visual acuity and intraocular pressure (IOP), were performed preoperatively, and at 1 day, at 1 week as well as at 1, 3, 6, 9, and 12 months postoperatively. Moreover, any goniopunctures and glaucoma medications required postoperatively were noted. RESULTS: The mean preoperative IOP was 20.8±5.2 mm Hg and it decreased to 13.9±3.1 mm Hg at 1 year postoperatively ( P <0.001). The number of glaucoma medications decreased from 2.9±0.7 preoperatively to 0.3±0.8 after 1 year ( P <0.001). The complete success rate (IOP≤21 mm Hg without glaucoma medication) and the qualified success rate (IOP ≤21 mm Hg with or without glaucoma medication) were 87.2% and 94.9%, respectively. Goniopuncture was performed in 33.3% of cases. No significant corrected visual acuity changes were registered at the final follow-up. Perioperative complications consisted of 3 micro-perforations of the trabeculo-descemet membrane. Postoperative complications included: hyphema (6 eyes), hypotony (6 eyes), shallow anterior chamber (3 eyes), choroidal detachment (4 eyes)-all of which were resolved without surgical intervention during the first postoperative month-and conjunctival dehiscence, which required resuture (2 eyes). CONCLUSION: Deep sclerectomy with the Esnoper Clip implant was safe and effectively lowered IOP in patients with uncontrolled POAG.


Subject(s)
Glaucoma, Open-Angle , Sclerostomy , Humans , Prospective Studies , Intraocular Pressure , Glaucoma, Open-Angle/surgery , Surgical Instruments , Treatment Outcome
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