RESUMEN
OBJECTIVE: To explore the clinical effect of percutaneous kyphoplasty (PKP) via process-rib-pedicle approach for upper and middle thoracic osteoporosis fractures with pedicle stenosis. METHODS: This study is a retrospective observational study. In this study, we retrospectively analyzed the data of 62 patients with upper thoracic vertebral bone loss compression fracture treated via the process-rib-pedicle pathway PKP at the First Affiliated Hospital of Soochow University from January 2020 to December 2022. The patients were divided into group A (unilateral PKP, 38 cases) and group B (bilateral PKP, 24 cases). The aspects of surgical safety, clinical efficacy, and radiological outcome were investigated. RESULTS: All 62 patients successfully completed the surgery without any spinal cord, nerve, or vascular injury, and there were no complications such as infection and vascular embolism. The differences in visual analog scale scoresï¼P < 0.05ï¼, Oswestry disability index functional indexï¼P < 0.05ï¼, and Cobb angleï¼P < 0.05ï¼ were significant when comparing preoperative and postoperative periods, and the differences were not significant when comparing the postoperative periods (P > 0.05). There were no statistically significant differences in days of hospital stay (P = 0.653) and the rate of bone cement leakage (P = 0.537) between the 2 groups. CONCLUSIONS: For upper middle osteoporotic thoracic vertebral fractures with pedicle stenosis, puncture via the process-rib-pedicle path is a safe and reliable puncture route, and more than 2.5 ml of cement can achieve good clinical outcomes, regardless of bilateral or unilateral PKP.
RESUMEN
This paper describes control methods to improve electric vehicle performance in terms of handling, stability and cornering by adjusting the weight distribution and implementing control systems (e.g., wheel slip control, and yaw rate control). The vehicle is first simulated using the bicycle model to capture the dynamics. Then, a study on the effect of weight distribution on the driving behavior is conducted. The study is performed for three different weight configurations. Moreover, a yaw rate controller and a wheel slip controller are designed and implemented to improve the vehicle's performance for cornering and longitudinal motion under the different loading conditions. The simulation through the bicycle model is compared to the experiments conducted on a rear-wheel driven radio-controlled (RC) electric vehicle. The paper shows how the wheel slip controller contributes to the stabilization of the vehicle, how the yaw rate controller reduces understeering, and how the location of the center of gravity (CoG) affects steering behavior. Lastly, an analysis of the combination of control systems for each weight transfer is conducted to determine the configuration with the highest performance regarding acceleration time, braking distance, and steering behavior.
RESUMEN
Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1-catalyzed RNA N7-methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non-ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac-specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC- or Mettl1-induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.
Asunto(s)
Cardiomegalia , Modelos Animales de Enfermedad , Animales , Cardiomegalia/genética , Cardiomegalia/metabolismo , Ratones , Factores de Empalme Serina-Arginina/metabolismo , Factores de Empalme Serina-Arginina/genética , Humanos , Metiltransferasas/metabolismo , Metiltransferasas/genética , Masculino , Factores de Transcripción NFATC/metabolismo , Factores de Transcripción NFATC/genética , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
Objectives: To explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR). Methods: We retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC. Results: The inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group. Conclusions: Retinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.
Asunto(s)
Coroides , Retinopatía Diabética , Retina , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/patología , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Coroides/patología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Retina/patología , Retina/diagnóstico por imagen , Anciano , Adulto , Densidad Microvascular , Estudios de Casos y Controles , Índice de Severidad de la Enfermedad , Angiografía con Fluoresceína/métodosRESUMEN
BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.
Asunto(s)
Pruebas Genéticas , Atrofia Muscular Espinal , Tamizaje Neonatal , Humanos , Recién Nacido , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Proyectos Piloto , Pruebas Genéticas/normas , Pruebas Genéticas/métodos , Tamizaje Neonatal/normas , Tamizaje Neonatal/métodos , China , Pruebas con Sangre Seca/normas , Pruebas con Sangre Seca/métodos , Garantía de la Calidad de Atención de Salud , Laboratorios Clínicos/normas , Proteína 1 para la Supervivencia de la Neurona Motora/genéticaRESUMEN
Biocatalysis within biphasic systems is gaining significant attention in the field of synthetic chemistry, primarily for its ability to solve the problem of incompatible solubilities between biocatalysts and organic compounds. By forming an emulsion from these two-phase systems, a larger surface area is created, which greatly improves the mass transfer of substrates to the biocatalysts. Among the various types of emulsions, Pickering emulsions stand out due to their excellent stability, compatibility with biological substances, and the ease with which they can be formed and separated. This makes them ideal for reusing both the emulsifiers and the biocatalysts. This review explores the latest developments in biocatalysis using Pickering emulsions. It covers the structural features, methods of creation, innovations in flow biocatalysis, and the role of interfaces in these processes. Additionally, the challenges and future directions are discussed in combining chemical and biological catalysts within Pickering emulsion frameworks to advance synthetic methodologies.
RESUMEN
Ferroptosis is a nonapoptotic form of regulated cell death that has been reported to play a central role in cardiac ischemiaâreperfusion (I/R) injury. N-acetyltransferase 10 (NAT10) contributes to cardiomyocyte apoptosis by functioning as an RNA ac4c acetyltransferase, but its role in cardiomyocyte ferroptosis during I/R injury has not been determined. This study aimed to elucidate the role of NAT10 in cardiac ferroptosis as well as the underlying mechanism. The mRNA and protein levels of NAT10 were increased in mouse hearts after I/R and in cardiomyocytes that were exposed to hypoxia/reoxygenation. P53 acted as an endogenous activator of NAT10 during I/R in a transcription-dependent manner. Cardiac overexpression of NAT10 caused cardiomyocyte ferroptosis to exacerbate I/R injury, while cardiomyocyte-specific knockout of NAT10 or pharmacological inhibition of NAT10 with Remodelin had the opposite effects. The inhibition of cardiomyocyte ferroptosis by Fer-1 exerted superior cardioprotective effects against the NAT10-induced exacerbation of post-I/R cardiac damage than the inhibition of apoptosis by emricasan. Mechanistically, NAT10 induced the ac4C modification of Mybbp1a, increasing its stability, which in turn activated p53 and subsequently repressed the transcription of the anti-ferroptotic gene SLC7A11. Moreover, knockdown of Mybbp1a partially abolished the detrimental effects of NAT10 overexpression on cardiomyocyte ferroptosis and cardiac I/R injury. Collectively, our study revealed that p53 and NAT10 interdependently cooperate to form a positive feedback loop that promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury, suggesting that targeting the NAT10/Mybbp1a/p53 axis may be a novel approach for treating cardiac I/R.
Asunto(s)
Ferroptosis , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Proteína p53 Supresora de Tumor , Animales , Humanos , Masculino , Ratones , Acetiltransferasas/metabolismo , Acetiltransferasas/genética , Apoptosis , Modelos Animales de Enfermedad , Retroalimentación Fisiológica , Ferroptosis/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
This work presents a resilient distributed optimization algorithm based on the event-triggering mechanism for cyber-physical systems (CPSs) to optimize an average of convex cost functions corresponding to multiple agents under adversarial environments. Two attack scenarios, including the f-total (each agent is affected by at most f malicious agents in the whole network) and the f-local (each agent is affected by at most f malicious agents in its in-neighbor set) attacks are considered. Subsequently, the convergence conditions under these two attack scenarios are provided, respectively, both of which guarantee that the state values of benign agents converge to a bounded error range. The optimality conditions are also presented by theoretical analysis, which guarantee that the state values of benign agents converge to a safety interval constructed by local optimal values under certain graph conditions, despite the misbehavior of malicious agents. In addition, four numerical examples are presented to show the effectiveness and superiority of the event-triggering resilient distributed optimization (RDO-E) algorithm. Compared to existing resilient algorithms, the proposed method achieves resilient distributed optimization with higher accuracy and less demanding communication overheads. Finally, by applying the proposed method to the multi-microgrid system, a resilient economic dispatch problem (REDP) is successfully solved, which validates the practical viability of the RDO-E algorithm.
RESUMEN
Background: Neonatal hyperbilirubinemia (NHB) is one of the most common diseases in the neonatal period. Without timely diagnosis and treatment, it can lead to long-term complications. In severe cases, it may even result in fatality. The UGT1A1 gene and clinical risk factors play important roles in the development and progression of NHB. Methods: In this study, we conducted a cohort study and analyzed 3258 newborns from the Jilin Women And Children Health Hospital in northern China, including 372 children with hyperbilirubinemia. We established a predictive model using a logistic regression model based on clinical risk factors and the polymorphism of the G211A locus in the UGT1A1 gene of newborns. Furthermore, the performance of the prediction model was evaluated using the ROC curve. Results: The logistic regression model indicates that the following factors are associated with an increased risk of NHB: the time when stool turns yellow [P ≤ 0.001, OR 1.266 (95% CI: 1.125-1.425)]; neonatal cephalohematoma [P ≤ 0.001, OR 33.642 (95% CI: 21.823-51.861)]; hemolytic disease of newborn [P ≤ 0.001, OR 33.849 (95% CI: 18.589-61.636)]; neonatal weight loss [P ≤ 0.001, OR 11.275 (95% CI: 7.842-16.209)]; neonatal premature rupture of membranes (PROM) history [P = 0.021, OR 1.422 (95% CI: 1.056-1.917)]; genetic polymorphism at the UGT1A1 gene G211A locus. Gestational age is a protective factor [P ≤ 0.001, OR 0.766 (95% CI: 0.686-0.855)]. Compared to natural labor, cesarean section is a protective factor [P = 0.011, OR 0.711 (95% CI: 0.546-0.926)], while assisted delivery is a risk factor [P = 0.022, OR 2.207 (95% CI: 1.121-4.346)]. The area under the curve (AUC) of this prediction model is 0.804 (95% CI: 0.777-0.831), indicating good discrimination ability and value for predicting the risk of NHB after birth. Conclusion: We have developed and evaluated a predictive model that combines UGT1A1 gene polymorphism and clinical risk factors for the first time. By using this nomogram and taking into account the results of serum total bilirubin measurement or transcutaneous bilirubin measurement, early prediction of the risk of neonatal hyperbilirubinemia can be achieved.
RESUMEN
Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.
RESUMEN
BACKGROUND: Programmed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC. METHODS: From July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes. RESULTS: A total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients. CONCLUSIONS: nCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined. TRIAL REGISTRATION NUMBER: NCT04437212.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Linfopenia , Trombocitopenia , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Cisplatino/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Terapia Neoadyuvante , Carcinoma de Células Escamosas/tratamiento farmacológico , Resultado del Tratamiento , Recurrencia Local de Neoplasia , Paclitaxel , Antígenos HLA-DR , Células Epiteliales/patologíaRESUMEN
INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.
RESUMEN
PURPOSE: To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. METHODS: A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. RESULTS: Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: ß coefficient = -0.351, p = 0.023; perifovea: ß coefficient = -0.338, p = 0.036). Perifoveal VLD (ß coefficient = -0.343, p = 0.031) and FD (ß coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (ß coefficient = -0.396, p = 0.008), perifoveal VLD (ß coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (ß coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (ß coefficient = -0.373, p = 0.023) and number of flow voids (ß coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. CONCLUSIONS: Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).
RESUMEN
Since the COVID-19 disease has been further aggravated, the prevention of pathogen transmission becomes a vital issue to restrain casualties. Recent research outcomes have shown the possibilities of the viruses existing on inanimate surfaces up to few days, which carry the risk of touch propagation of the disease. Deep ultraviolet germicide irradiation (UVGI) with the wavelength of 255-280nm has been verified to efficiently disinfect various types of bacteria and virus, which could prevent the aggravation of pandemic spread. Even though considerable experiments and approaches have been applied to evaluate the disinfection effects, there are only few reports about how the individual bio-organism behaves after ultraviolet C (UVC) irradiation, especially in the aspect of mechanical changes. Furthermore, since the standard pathway of virus transmission and reproduction requires the host cell to assemble and transport newly generated virus, the dynamic response of infectious cell is always the vital aspect of virology study. In this work, high power LEDs array has been established with 270nm UVC irradiation to evaluate disinfection capability on various types of bio-organism, and incubator embedded atomic force microscopy (AFM) is used to investigate the single bacterium and virus under UVGI. The real-time tracking of the living Vero cells infected with adenovirus has also been presented in this study. The results show that after sufficient UVGI, the outer shell of bacteria and viruses remain intact in structure, however the bio-organisms lost the capability of reproduction and normal metabolism. The experiment results also indicate that once the host cell is infected with adenovirus, the rapid production of newborn virus capsid will gradually destroy the cellular normal metabolism and lose mechanical integrity.
Asunto(s)
Desinfección , Virus , Humanos , Chlorocebus aethiops , Recién Nacido , Animales , Desinfección/métodos , Células Vero , Rayos Ultravioleta , Bacterias , BiomarcadoresRESUMEN
AIMS: To evaluate the efficacy and safety of intravitreal triamcinolone acetonide (TA) injection at the end of emergency surgery for open globe injury (OGI) to suppress traumatic proliferative vitreoretinopathy (TPVR). METHODS: A single-centre, participant-masked, prospective, randomised controlled clinical trial. A total of 68 globe rupture patients with zone III were randomised to the control group (n=34) or the TA group (n=34) in 1:1 allocation ratio. Patients were treated with 0.1 mL TA in the TA group and 0.1 mL balanced salt solution in the control group at the end of emergency surgery. The primary outcome was the assessment of TPVR during vitrectomy 10±3 days later. Secondary outcomes included visual acuity (VA), retinal attachment rate, macular attachment rate, proliferative vitreoretinopathy (PVR) recurrent rate, side effects 6 months after vitrectomy. RESULTS: During vitrectomy, the TPVR grade of the control group was significantly more severe than the TA group (p=0.028). The TPVR score was significantly better in the TA group (9.30±0.82) than in the control group (6.44±1.06) (p=0.036). The final VA improved in 23 eyes (92%) in the TA group and in 14 eyes (63.64%) in the control group (p=0.008). The retinal attachment rates were 88% and 63.64% in the TA and control group, respectively (p=0.049). The two groups showed no significant difference in macular repositioning and PVR recurrent rate (p=0.215, 0.191). Temporary intraocular pressure elevation occurred in one eye in the TA group after emergency surgery. CONCLUSIONS: Early intravitreal TA injection for OGI effectively reduces TPVR, increases surgical success and improves visual prognosis.
RESUMEN
Donafenib and sorafenib are small molecule chemotherapy drugs for the management of hepatocellular carcinoma, with donafenib being a deuterated derivative of sorafenib. To date, a high liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method that quantify donafenib, sorafenib, and their main metabolites has not yet been developed. The objective of this study was to establish a HPLC-MS/MS method for the simultaneous detection of donafenib, donafenib-N-oxide, sorafenib, and sorafenib-N-oxide and for the pharmacokinetic studies in rat. The extraction of all analytes was achieved by simple protein precipitation utilizing acetonitrile. The Waters XBridge C18 column (2.1 × 100 mm, 3.5 µm) was selected, and the analytes could be efficiently separated and quantitated during a 2.8 min gradient elution procedure. The method was linear within the predefined quantification ranges and provided acceptable precision (%CV < 9.4%), reproducible extraction recovery (99.4%-111.5%), and low matrix effect (88.1%-98.6%). The hemolysis effect did not interfere with the quantification of all analytes, and similar results were obtained by changing the anticoagulant K2-EDTA to heparin or sodium citrate. Plasma pharmacokinetics revealed that the values of t1/2, Cmax, and AUC0-t of donafenib were 1.4-, 6.2-, and 3.1-fold higher than those of sorafenib, respectively. In conclusion, the proposed bioassay was successfully applied to pharmacokinetic studies in rat after administration of donafenib and sorafenib. Our work not only improves the bioanalytical method for determining the plasma concentrations of donafenib, sorafenib, and their N-oxide metabolites, but also provides a scientific reference for clinical pharmacokinetic studies.
Asunto(s)
Óxidos , Espectrometría de Masas en Tándem , Ratas , Animales , Sorafenib , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Reproducibilidad de los ResultadosRESUMEN
Background: Orientia tsutsugamushi is a zoonotic intracellular pathogen that requires parasitism in eukaryotic cells to reproduce. In recent years, tsutsugamushi disease reported in many places nationwide has crossed the Yangtze River, continuously, spreading to the North China. Now this phenomenon has aroused people's attention. Materials and Methods: In this study, meta-analysis was used to analyze the infection of rodents (vectors) in China, to clarify the transmission rule of O. tsutsugamushi. Results: This study included literature from six databases (PubMed, Web of Science, Science Direct, Wanfang, CNKI, and VIP). A total of 55 articles were included in the study from 610 retrieved articles. The total infection rate of O. tsutsugamushi in rodents was 5.5% (1206/20,620, 95% confidence interval [CI]: 0.0553-0.0617). The prevalence of O. tsutsugamushi in rodents before 2013 (7.73%, 95% CI: 4.11-12.37) was higher than after 2013 (2.11%, 95% CI: 0.64-4.41). O. tsutsugamushi spread among a variety of rodents, among which Rattus losea (13.3%, 95% CI: 4.33-26.26), Rattus tanezumi (5.69%, 95% CI: 1.37-12.72), and Apodemus agrarius (5.32%, 95% CI: 2.26-9.58) infection rate was higher. Kawasaki (8.32%, 95% CI: 1.42-20.17), Karp (7.36%, 95% CI: 2.62-14.22), Kato (2.54%, 95% CI: 0.08-8.28), and Gilliam (2.13%, 95% CI: 0.42-5.09) were the main prevalent genotypes in China. The prevalence of O. tsutsugamushi in rodents was seasonal, increasing gradually in summer (2.39%, 95% CI: 0.46-5.77), peaking in autumn (4.59%, 95% CI: 1.15-10.16), and then declining. The positive rate of immunofluorescence assay (25.07%, 95% CI: 8.44-46.88) was the highest among the detection methods, and it was statistically significant (p < 0.05). Based on the subgroup of geographical factors and climatic factors, the probability of O. tsutsugamushi infection in rodents was the highest when the temperature >19â (8.20%, 95% CI: 1.22-20.52), the altitude <100 millimeters (7.23%, 95% CI: 3.45-12.26), the precipitation >700 millimeters (12.22%, 95% CI: 6.45-19.50), and the humidity 60-70% (7.80%, 95% CI: 4.17-12.44). Conclusions: Studies have shown that rodents carrying O. tsutsugamushi are common. People should prevent and control rodents in life and monitor rodents carrying O. tsutsugamushi for a long time.
Asunto(s)
Orientia tsutsugamushi , Tifus por Ácaros , Trombiculidae , Animales , Humanos , Orientia tsutsugamushi/genética , Prevalencia , Tifus por Ácaros/epidemiología , Tifus por Ácaros/veterinaria , Murinae , China/epidemiologíaRESUMEN
Ischemic heart failure (HF) remains a leading cause of morbidity and mortality. Maintaining homeostasis of cardiac function and preventing cardiac remodeling deterioration are critical to halting HF progression. Methyltransferase-like protein 13 (Mettl13) has been shown to regulate protein translation efficiency by acting as a protein lysine methyltransferase, but its role in cardiac pathology remains unexplored. This study aims to characterize the roles and mechanisms of Mettl13 in cardiac contractile function and HF. We found that Mettl13 was downregulated in the failing hearts of mice post-myocardial infarction (MI) and in a cellular model of oxidative stress. Cardiomyocyte-specific overexpression of Mettl13 mediated by AAV9-Mettl13 attenuated cardiac contractile dysfunction and fibrosis in response to MI, while silencing of Mettl13 impaired cardiac function in normal mice. Moreover, Mettl13 overexpression abrogated the reduction in cell shortening, Ca2+ transient amplitude and SERCA2a protein levels in the cardiomyocytes of adult mice with MI. Conversely, knockdown of Mettl13 impaired the contractility of cardiomyocytes, and decreased Ca2+ transient amplitude and SERCA2a protein expression in vivo and in vitro. Mechanistically, Mettl13 impaired the stability of c-Cbl by inducing lysine methylation of c-Cbl, which in turn inhibited ubiquitination-dependent degradation of SERCA2a. Furthermore, the inhibitory effects of knocking down Mettl13 on SERCA2a protein expression and Ca2+ transients were partially rescued by silencing c-Cbl in H2O2-treated cardiomyocytes. In conclusion, our study uncovers a novel mechanism that involves the Mettl13/c-Cbl/SERCA2a axis in regulating cardiac contractile function and remodeling, and identifies Mettl13 as a novel therapeutic target for ischemic HF.
Asunto(s)
Insuficiencia Cardíaca , Peróxido de Hidrógeno , Ratones , Animales , Peróxido de Hidrógeno/metabolismo , Insuficiencia Cardíaca/etiología , Miocitos Cardíacos/metabolismo , Ubiquitinación , Metiltransferasas/genéticaRESUMEN
Ferroptosis is a pervasive non-apoptotic mode of cell death that is different from autophagy or necrosis. It is mainly caused by an imbalance between the production and degradation of lipid reactive oxygen species in cells. Several metabolic pathways and biochemical processes, such as amino acid and lipid metabolism, iron handling, and mitochondrial respiration, affect and regulate cell sensitivity to peroxidation and ferroptosis. Organ fibrosis, a pathological manifestation of several etiological conditions, leads to chronic tissue injury and is characterized by excessive deposition of extracellular matrix components. Excessive tissue fibrosis can have diverse pathophysiological effects on several organ systems, eventually causing organ dysfunction and failure. The current manuscript provides a review that illustrates the link between ferroptosis and organ fibrosis and to better understand the underlying mechanisms. It provides novel potential therapeutic approaches and targets for fibrosis diseases.
Asunto(s)
Ferroptosis , Humanos , Muerte Celular , Hierro/metabolismo , Necrosis , Especies Reactivas de Oxígeno/metabolismo , Fibrosis , Peroxidación de Lípido/fisiologíaRESUMEN
BACKGROUND: Radiotherapy is an essential treatment for chest cancer. Radiation-induced pulmonary fibrosis (RIPF) is an almost irreversible interstitial lung disease; however, its pathogenesis remains unclear. METHODS: We analyzed specific changes in cell populations and potential markers by using single-cell sequencing datasets from the Sequence Read Archive database, PERFORMED from control (0 Gy) and thoracic irradiated (20 Gy) mouse lungs at day 150 post-radiation. We performed IHC and ELISA on lung tissue and cells to validate the potential marker cytokines identified by the analysis on rat thoracic irradiated molds (30 Gy). RESULTS: Single-cell sequencing analysis showed changes in abundance across cell types and at the single-cell level, with B and T cells showing the most significant changes in abundance. And four cytokines, CCL5, ICAM1, PF4, and TNF, were significantly upregulated in lung tissues of RIPF rats and cell supernatants after ionizing radiation. CONCLUSION: Cytokines CCL5, ICAM1, PF4, and TNF may play essential roles in radiation pulmonary fibrosis. They are potential targets for the treatment of radiation pulmonary fibrosis.