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BACKGROUND: Dyslipidemia is a common complication in patients with diabetes mellitus (DM) that increases the risk of cardiovascular disease. Genetic polymorphisms have been implicated in the development of dyslipidemia. AIM: To investigate the association between polymorphisms of candidate genes involved in lipid metabolism and dyslipidemia in Chinese patients with DM. METHODS: A cross-sectional study was conducted on 1098 Chinese patients with DM recruited from multiple healthcare centers. Demographic and clinical data were collected, and dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Genomic DNA was extracted from blood samples and genotyping for selected polymorphisms of candidate genes (APOE, LPL, CETP, and others) was performed using PCR and DNA sequencing techniques. Statistical analyses were performed using logistic regression models adjusted for potential confounding factors. RESULTS: The study population consisted of 578 males (52.6%) and 520 females (47.4%), with a mean age of 58.4 ± 12.2 years. The prevalence of dyslipidemia was 64.8%. Significant associations were found between dyslipidemia and the APOE rs7412 T/T, APOE rs429358 C/C, LPL rs328 G/G, and CETP rs708272 G/G genotypes after adjusting for covariates. Subgroup analyses showed generally consistent associations across subgroups, although some variations in effect sizes were observed. CONCLUSION: This study identified significant associations between genetic polymorphisms of APOE, LPL, and CETP genes and dyslipidemia in Chinese patients with DM.
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Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.
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Radioisótopos de Cesio , Minería , Contaminantes Radiactivos del Suelo , Medición de Riesgo , China , Contaminantes Radiactivos del Suelo/análisis , Radioisótopos de Cesio/análisis , Humanos , Radioisótopos de Estroncio/análisis , Cesio/análisis , Ciudades , Suelo/química , Método de Montecarlo , Monitoreo de RadiaciónRESUMEN
A label-free fluorescent sensing strategy for the rapid and highly sensitive detection of Pb2+ was developed by integrating Pb2+ DNAzyme-specific cleavage activity and a tetrahedral DNA nanostructure (TDN)-enhanced hyperbranched hybridization chain reaction (hHCR). This strategy provides accelerated reaction rates because of the highly effective collision probability and enriched local concentrations from the spatial confinement of the TDN, thus showing a higher detection sensitivity and a more rapid detection process. Moreover, a hairpin probe based on a G-triplex instead of a G-quadruplex or chemical modification makes hybridization chain reaction more controlled and flexible, greatly improving signal amplification capacities and eliminating labeled DNA probes. The enhanced reaction rates and improved signal amplification efficiency endowed the biosensors with high sensitivity and a rapid response. The label-free detection of Pb2+ based on G-triplex combined with thioflavin T can be achieved with a detection limit as low as 1.8 pM in 25 min. The proposed Pb2+-sensing platform was also demonstrated to be applicable for Pb2+ detection in tap water, river water, shrimp, rice, and soil samples, thus showing great potential for food safety and environmental monitoring.
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Técnicas Biosensibles , ADN Catalítico , Plomo , Límite de Detección , Hibridación de Ácido Nucleico , Plomo/análisis , Plomo/química , ADN Catalítico/química , Técnicas Biosensibles/métodos , Nanoestructuras/química , Contaminantes Químicos del Agua/análisis , ADN/química , ADN/análisis , Animales , Monitoreo del Ambiente/métodos , Oryza/química , Contaminantes Ambientales/análisisRESUMEN
Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.
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Mitocondrias , Nitrilos , Proteínas Quinasas , Piretrinas , Piretrinas/toxicidad , Mitocondrias/efectos de los fármacos , Animales , Nitrilos/toxicidad , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Enfermedades Neuroinflamatorias/inducido químicamente , Insecticidas/toxicidad , Ratones , Especies Reactivas de Oxígeno/metabolismo , Inflamación/inducido químicamente , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genéticaRESUMEN
Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is the most abundant free amino acid in the body and participates in more metabolic processes than other amino acids. Altered glutamine metabolism is a prominent feature in different kidney diseases. Glutaminolysis converts glutamine into the TCA cycle metabolite, alpha-ketoglutarate, via a cascade of enzymatic reactions. This metabolic pathway plays pivotal roles in inflammation, maladaptive repair, cell survival and proliferation, redox homeostasis, and immune regulation. Given the crucial role of glutaminolysis in bioenergetics and anaplerotic fluxes in kidney pathogenesis, studies on this cascade could provide a better understanding of kidney diseases, thus inspiring the development of potential methods for targeted therapy. Emerging evidence has shown that targeting glutaminolysis is a promising therapeutic strategy for ameliorating kidney disease. In this narrative review, equation including keywords related to glutamine, glutaminolysis and kidney are subjected to an exhaustive search on Pubmed database, we identified all relevant articles published before 1 April, 2024. Afterwards, we summarize the regulation of glutaminolysis in major kidney diseases and its underlying molecular mechanisms. Furthermore, we highlight therapeutic strategies targeting glutaminolysis and their potential clinical applications.
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The performance of biochar (BC) in reducing the transport of antibiotics under field conditions has not been sufficiently explored. In repacked sloping boxes of a calcareous soil, the effects of different BC treatments on the discharge of three relatively weakly sorbing antibiotics (sulfadiazine, sulfamethazine, and florfenicol) via runoff and drainage were monitored for three natural rain events. Surface application of 1 % BC (1 %BC-SA) led to the most effective reduction in runoff discharge of the two sulfonamide antibiotics, which can be partly ascribed to the enhanced water infiltration. The construction of 5 % BC amended permeable reactive wall (5 %BC-PRW) at the lower end of soil box was more effective than the 1 %BC-SA treatment in reducing the leaching of the most weakly sorbing antibiotic (florfenicol), which can be mainly ascribed to the much higher plant available and drainable water contents in the 5 %BC-PRW soil than in the unamended soil. The results of this study highlight the importance of BC's ability to regulate flow pattern by modifying soil hydraulic properties, which can make a significant contribution to the achieved reduction in the transport of antibiotics offsite or to groundwater.
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Antibacterianos , Carbón Orgánico , Contaminantes del Suelo , Suelo , Antibacterianos/química , Carbón Orgánico/química , Adsorción , Suelo/química , Contaminantes del Suelo/química , Contaminantes Químicos del Agua/química , Movimientos del Agua , Agua Subterránea/química , Tianfenicol/análogos & derivados , Tianfenicol/químicaRESUMEN
OBJECTIVE: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). MATERIALS AND METHODS: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. RESULTS: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. CONCLUSIONS: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.
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Carcinoma , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/mortalidad , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Carcinoma/radioterapia , Carcinoma/secundario , Carcinoma/mortalidad , Adulto , Anciano , Puntaje de Propensión , Pronóstico , Tasa de Supervivencia , Neoplasias Óseas/secundario , Neoplasias Óseas/radioterapia , Neoplasias Óseas/mortalidad , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Resultado del Tratamiento , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/mortalidadRESUMEN
Long interspersed elements-1(LINE-1) is the only autonomous transposon in human genomeï¼and its retrotransposition results in change of cellular genome structure and function, leading occurrence of various severe diseases. As a central key intermediated component during life cycle of LINE-1 retrotransposition, the host modification of LINE-1 mRNA affects the LINE-1 transposition directly. N6-adenosine methylation(m6A), the most abundant epigenetic modification on eukaryotic RNA, is dynamically reversible. m6A modification is also found on LINE-1 mRNA, and it participants regulation of the whole LINE-1 replication cycle, with affecting LINE-1 retrotransposition as well as its adjacent genes expression, followed by influencing genomic stability, cellular self-renewal, and differentiation potential, which plays important roles in human development and diseases. In this review, we summarize the research progress in LINE-1 m6A modification, including its modification positions, patterns and related mechanisms, hoping to provide a new sight on the mechanism research and treatment of related diseases.
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Adenosina/análogos & derivados , Genoma Humano , ARN , Humanos , Metilación , ARN/metabolismo , ARN Mensajero/genéticaRESUMEN
OBJECTIVES: Residual varus after total knee arthroplasty (TKA) can affect functional outcomes, which may worsen in the presence of obesity. However, no studies were found to compare the outcomes of obese patients involving postoperative residual mild varus or neutral. The aim of this study was to compare postoperative complications and prosthesis survival, and functional outcomes for knees of obese patients with neutral or mild varus after TKA. METHODS: We retrospectively reviewed 188 consecutive obese patients (body mass index ≥30 kg/m2) at our hospital who underwent TKA due to varus knee osteoarthritis from January 2010 to December 2015. The mechanical hip-knee-ankle axis angle was measured in all patients at admission and discharge. Knee functions were retrospectively assessed based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society Knee Score (KS-KS), Knee Society Function Score (KS-FS), Forgotten Joint Score (FJS), and range of motion (ROM). Continuous data were compared between knees with neutral or mild varus alignment using analysis of Student's t test or variance or the Kruskal-Wallis test as appropriate. For multiple comparisons of outcomes, we used Bonferroni-Dunn method to adjust p-values. Categorical data were compared using the chi-squared test. RESULTS: Of the 156 knees in 137 obese patients who completed follow-up for a mean of 8.32 ± 1.47 years, 97 knees were corrected from varus to neutral and 54 knees were kept in mild residual varus. Patients with mild varus knees had significantly WOMAC (8.25 ± 8.637 vs. 14.97 ± 14.193, p = 0.009) and better FJS (86.03 ± 15.607 vs. 70.22 ± 30.031, p = 0.002). The two types of knees did not differ significantly in KS-KS, KS-FS, or ROM. Although one patient with a neutral knee had to undergo revision surgery, there was no significant difference between two groups. CONCLUSIONS: For obese patients with osteoarthritis, preservation of residual varus alignment after TKA can improve functional outcomes without compromising prosthesis survival.
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Artroplastia de Reemplazo de Rodilla , Obesidad , Osteoartritis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/cirugía , Osteoartritis de la Rodilla/cirugía , Estudios de Seguimiento , Complicaciones Posoperatorias , Rango del Movimiento Articular , Prótesis de la Rodilla , Falla de PrótesisRESUMEN
Ferroptosis is a newly identified form of non-apoptotic regulated cell death (RCD) andplaysanimportantrole in epileptogenesis. The p38 mitogen-activated protein kinase (p38 MAPK) pathway has been confirmed to be involved in ferroptosis. The mitochondria-targeting antioxidant Elamipretide (SS-31) can reduce the generation of lipid peroxidation and the buildup of reactive oxygen species (ROS). Collectively, our present study was to decipher whether SS-31 inhibits ferroptosis via the p38 MAPK signaling pathway in the rat epilepsy model induced by pilocarpine (PILO).Adult male Wistar rats were randomly divided into four groups: control group (CON group), epilepsy group (EP group), SS-31 treatment group (SS group), and p38 MAPK inhibitor (SB203580) treatment group (SB group). Our results demonstrated that the rat hippocampal neurons after epilepsy were followed by accumulated iron and malondialdehyde (MDA) content, upregulated phosphorylated p38 MAPK protein (P-p38) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels, reduced glutathione peroxidase 4 (Gpx4) content, and depleted glutathione (GSH) activity. Morphologically, mitochondrial ultrastructural damage under electron microscopy was manifested by a partial increase in outer membrane density, disappearance of mitochondrial cristae, and mitochondrial shrinkage. SS-31 and SB203580 treatment blocked the initiation and progression of ferroptosis in the hippocampus of epileptic rats via reducing the severity of epileptic seizures, reversing the expression of Gpx4, P-p38 , decreasing the levels of iron and MDA, as well as increasing the activity of GSH and Nrf2. To summarize, our findings proved that ferroptosis was coupled with the pathology of epilepsy, and SS-31 can inhibit PILO-induced seizures by preventing ferroptosis, which may be connected to the inhibition of p38 MAPK phosphorylation, highlighting the potential therapeutic value for targeting ferroptosis process in individuals with seizure-related diseases.
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Epilepsia , Ferroptosis , Hipocampo , Mitocondrias , Ratas Wistar , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Masculino , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Ferroptosis/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Ratas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Dipéptidos/farmacología , Pilocarpina , Imidazoles/farmacología , Piridinas/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , OligopéptidosRESUMEN
Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery.
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Alcaloides , Corydalis , Corydalis/química , Proteínas Quinasas Activadas por AMP/metabolismo , Alcaloides/química , Espectroscopía de Resonancia Magnética , AutofagiaRESUMEN
BACKGROUND: Stem cell therapy has shown great potential for treating diabetic foot (DF). AIM: To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades, with the aim of depicting the current global research landscape, identifying the most influential research hotspots, and providing insights for future research directions. METHODS: We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF. Bibliometric analysis was carried out using CiteSpace, VOSviewer, and R (4.3.1) to identify the most notable studies. RESULTS: A search was conducted to identify publications related to the use of stem cells for DF treatment. A total of 542 articles published from 2000 to 2023 were identified. The United States had published the most papers on this subject. In this field, Iran's Shahid Beheshti University Medical Sciences demonstrated the highest productivity. Furthermore, Dr. Bayat from the same university has been an outstanding researcher in this field. Stem Cell Research & Therapy is the journal with the highest number of publications in this field. The main keywords were "diabetic foot ulcers," "wound healing," and "angiogenesis." CONCLUSION: This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years. Current research findings suggested that the hotspots in this field include stem cell dressings, exosomes, wound healing, and adipose-derived stem cells. Future research should also focus on the clinical translation of stem cell therapies for DF.
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Luminescent metal clusters have attracted great interest in current research; however, the design synthesis of Al clusters with color-tunable luminescence remains challenging. Herein, an [Al8 (OH)8 (NA)16 ] (Al8 , HNA = nicotinic acid) molecular cluster with dual luminescence properties of fluorescence and room-temperature phosphorescence (RTP) is synthesized by choosing HNA ligand as phosphor. Its prompt photoluminescence (PL) spectrum exhibits approximately white light emission at room temperature. Considering that halogen atoms can be used to regulate the RTP property by balancing the singlet and triplet excitons, different CdX2 (X- = Cl- , Br- , I- ) are introduced into the reactive system of the Al8 cluster, and three new Al8 cluster-based metal-organic frameworks, {[Al8 Cd3 Cl5 (OH)8 (NA)17 H2 O]·2HNA}n (CdCl2 -Al8 ), {[Al8 Cd4 Br7 (OH)8 (NA)16 CH3 CN]·NA·HNA}n (CdBr2 -Al8 ) and {[Al8 Cd8 I16 (OH)8 (NA)16 ]}n (CdI2 -Al8 ) are successfully obtained. They realize the color tunability from blue to yellow at room temperature. The origination of fluorescence and phosphorescence has also been illustrated by structure-property analysis and theoretical calculation. This work provides new insights into the design of multicolor luminescent metal cluster-based materials and develops advanced photo-functional materials for multicolor display, anti-counterfeiting, and encryption applications.
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OBJECTIVES: This study overviewed the current database of studies on periprosthetic joint infections (PJIs) to compare outcomes and antibiotic side effects in culture-negative or culture-positive PJIs and assess treatment options for culture-negative PJIs. PATIENTS AND METHODS: A systematic review and meta-analysis was undertaken using studies published before July 2022 in MEDLINE, EMBASE, and Cochrane Library. All studies comparing treatment of culture-negative or -positive PJIs were included. Afterward, the infection control rate, periprosthetic or spacer fracture, hip joint or spacer dislocation, and antibiotic side effects in different treatment methods of PJI were analyzed. RESULTS: Eleven studies involving 1,747 patients were included. Most studies clearly defined the infection control criteria: no pain or swelling, no wound drainage, normal serology, and normal radiographic findings. Patients were followed until treatment failure, death, or until the last clinical visit without evidence of treatment failure. The two types of PJIs did not differ significantly in infection control rates (culture-negative PJI 79.2% vs. culture-positive PJI 76.6%; odds ratio [OR]=1.20, 95% confidence interval [CI]: 0.84 to 1.70), either after all types of surgical treatment or after two-stage revision arthroplasty (OR=1.12, 95% CI: 0.72 to 1.75), single-stage revision arthroplasty (OR=0.51, 95% CI: 0.19 to 1.37), or debridement, antibiotics, and implant retention (OR=0.88, 95% CI: 0.50 to 1.54). Similarly, we did not find differences in periprosthetic or spacer fracture and hip joint or spacer dislocation. For culture-negative PJIs, the infection control rate was 85.2% after two-stage revision arthroplasty, 90.6% after single-stage revision arthroplasty, and 69.7% after debridement, antibiotics, and implant retention. Data pooled from three studies showed higher incidence of antibiotic side effects for culture-negative PJIs. CONCLUSION: The clinical outcomes of one-stage revision and two-stage revision are comparable. Therefore, both of them can be considered in surgical treatment for culture-negative PJIs. In addition, limited data showed a higher incidence of antibiotic side effects in culture-negative PJIs.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Antibacterianos/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Articulación de la Cadera/cirugía , Prótesis e Implantes/efectos adversos , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugíaRESUMEN
BACKGROUND: Transplacental-derived anti-D IgG in RhD-negative pregnant women can trigger an immune response to Rh D-positive red cells in fetuses and newborns. We assessed the effect of anti-D titers in RhD-negative pregnant women on fetuses and newborns. METHODS: The clinical data of 142 singleton RhD-sensitized pregnancies were retrospectively collected. The pregnant women received routine prenatal care and the newborns had standard care. Based on the tertile categories of the pregnancies, the maximum titers of anti-D IgG in the pregnant women were divided into three groups ranging from low to high as follows: low-titer group (anti-D titer: 1:4-1:128, n = 57); medium-titer group (anti-D titer: 1:256-1:512, n = 50); and high-titer group (anti-D titer: 1:1024-1:4096, n = 35). RESULTS: The frequencies of major neonatal complications did not significantly differ among the three groups. The high-titer group had the highest frequency of pregnancies requiring intrauterine transfusion (IUT) and number of IUTs among the three groups. The high-titer group had a significantly higher frequency of newborns treated with top-up transfusion, number of top-up transfusions, frequency of newborns treated with exchange transfusion (ET), and number of ETs when compared to the low-titer group. CONCLUSION: Higher anti-D titers in RhD-negative pregnant women predict more severe fetal and neonatal hemolytic anemia. Increasing maternal anti-D titers results in an increased need for IUTs, and neonatal top-up transfusions and ETs. Methods for reducing titers of anti-D IgG in RhD-sensitized pregnant women warrants further investigation.
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PURPOSE: To investigate the effect of the optional biometric parameters lens thickness (LT) and center corneal thickness (CCT) in the Kane formula on intraocular lens (IOL) power calculation. METHODS: A cross-sectional study included consecutive cataract patients who received uncomplicated cataract surgery with IOL implantation from May to September 2022 were enrolled. The ocular biometric parameters were obtained using IOLMaster 700 and then inputted into online Kane formula calculator. The IOL power was calculated for targeting emmetropia and compared between groups: not omitting (NO) group, omitting LT and CCT (OLC) group, omitting LT (OL) group and omitting CCT (OC) group. Further, according to the axial length (AL), anterior chamber depth (ACD), and mean keratometry (Km), the eyes were divided into three subgroups, respectively. RESULTS: 1005 eyes of 1005 consecutive patients were included. There was no significant difference in IOL power between NO group and OC group (P = 0.064), and the median absolute difference (MedAD) was 0.05D. The IOL power in NO group showed significant differences from OLC group and OL group respectively (P < 0.001), and both MedAD values were 0.18D. Among AL subgroups, MedAD ranged from 0.06D to 0.35D in short eyes. Among ACD subgroups, the above values ranged from 0.06D to 0.23D in shallow ACD subgroup. Among Km subgroups, these values ranged from 0.05D to 0.31D in steep Km subgroup. CONCLUSION: The optional biometric parameter CCT has no effect on the calculation results of the Kane formula, whereas the parameter LT has a great influence on the Kane formula results for the IOL power calculation in cataract patients with short AL, shallow ACD and steep Km.
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Catarata , Lentes Intraoculares , Humanos , Estudios Transversales , Ojo , BiometríaRESUMEN
OBJECTIVES: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. METHODS: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. RESULTS: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance. CONCLUSION: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.
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Trasplante de Riñón , Modelos Biológicos , Humanos , Adulto , Linezolid/uso terapéutico , Teorema de Bayes , Simulación por Computador , Trasplante de Riñón/efectos adversosRESUMEN
OBJECTIVE: To assess the clinical efficacy of fucoidan-assisted standard quadruple therapy (SQT) in Helicobacter pylori (H. pylori) eradication and the improvement of gut microbiota. METHODS: An open-label randomized controlled trial was conducted at the Affiliated Hospital of Qingdao University in Shandong Province, China. Ninety patients who tested positive for H. pylori were randomized to the standard quadruple therapy (SQT) group (SQ), SQT + fucoidan combination group (SF), and fucoidan + sequential SQT group (FS), respectively. Stool samples were collected for gut microbiota composition at baseline and after treatment. RESULTS: After H. pylori eradication, the relative abundances of most conditional pathogens in the SQ decreased, while those of several beneficial bacteria increased or decreased (P < 0.05). In FS, the abundances of most beneficial bacteria increased gradually from baseline to week 12, while those of the conditional pathogens decreased (P < 0.05). The abundance of Bifidobacterium had a decreasing trend in SQ, but remained unchanged in SF and increased in FS (P < 0.05). The abundances of most beneficial bacteria were significantly higher in FS than in SQ and SF (P < 0.05). Addition of fucoidan enhanced symptom improvement during H. pylori eradication compared with SQT alone. CONCLUSIONS: Fucoidan considerably improved gut dysbiosis during SQT for H. pylori eradication. Gut microbiota can be maintained by the addition of fucoidan before eradication therapy with SQT rather than by concomitant addition with therapy. Fucoidan-assisted SQT could relieve gastrointestinal symptoms during H. pylori eradication.
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Experimental evidence has demonstrated that neonicotinoids (NEOs) exposure can cause lipid accumulation and increased leptin levels. However, the relationship between NEOs exposure and dyslipidemia in humans remains unclear, and the interactive effects of NEOs and their characteristic metabolites on dyslipidemia remain unknown. We detected 14 NEOs and their metabolites in urine samples of 500 individuals (236 and 264 with and without dyslipidemia, respectively) randomly selected from the baseline of the Yinchuan community-dwelling elderly cohort (Ningxia, China). The NEOs and their metabolites were widely detected in urine (87.2-99.6 %) samples, and the median levels ranged within 0.06-0.55 µg/g creatinine. The positive associations and dose-dependent relationships of thiacloprid, imidacloprid-olefin, and imidacloprid-equivalent total with dyslipidemia were validated using restricted cubic spline analysis. Mixture models revealed a positive association between the NEOs mixture and dyslipidemia risk, with urine desnitro-imidacloprid ranked as the top contributor. The Bayesian Kernel Machine Regression models showed that the NEOs mixtures were associated with increased dyslipidemia when the chemical mixtures were ≥ 25th percentile compared to their medians, and desnitro-imidacloprid and imidacloprid-olefin were the major contributors to the combined effect. Given the widespread use of NEOs and the dyslipidemia pandemic, further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms.