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Objective: To investigate the diagnostic efficacy of the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model based on ultrasonographic radiomics for the differentiation of small clear cell Renal Cell Carcinoma (ccRCC) and Renal Angiomyolipoma (RAML). Methods: The clinical, ultrasound, and contrast-enhanced CT(CECT) imaging data of 302 small renal tumors (maximum diameter ≤ 4cm) patients in Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2022 were retrospectively analyzed, with 182 patients of ccRCC and 120 patients of RAML. The ultrasound images of the largest diameter of renal tumors were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from ROI segmented images. The patients were randomly divided into training and internal validation cohorts in the ratio of 7:3. The Random Forest algorithm of the Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model. The efficacy of the prediction models was verified in an independent external validation cohort consisting of 69 patients, from 230 small renal tumor patients in two different institutions. The Delong test compared the predictive ability of three models and CECT. Calibration Curve and clinical Decision Curve Analysis were applied to evaluate the model and determine the net benefit to patients. Results: 491 ultrasonographic radiomics features were extracted from 302 small renal tumor patients, and 9 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. In the internal validation cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy of the clinical ultrasound imaging model, ultrasonographic radiomics model, comprehensive model, and CECT were 0.75, 76.7%, 60.0%, 70.0%; 0.80, 85.6%, 61.7%, 76.0%; 0.88, 90.6%, 76.7%, 85.0% and 0.90, 92.6%, 88.9%, 91.1%, respectively. In the external validation cohort, AUC, sensitivity, specificity, and accuracy of the three models and CECT were 0.73, 67.5%, 69.1%, 68.3%; 0.89, 86.7%, 80.0%, 83.5%; 0.90, 85.0%, 85.5%, 85.2% and 0.91, 94.6%, 88.3%, 91.3%, respectively. The DeLong test showed no significant difference between the clinical ultrasound imaging model and the ultrasonographic radiomics model (Z=-1.287, P=0.198). The comprehensive model showed superior diagnostic performance than the ultrasonographic radiomics model (Z=4. 394, P<0.001) and the clinical ultrasound imaging model (Z=4. 732, P<0.001). Moreover, there was no significant difference in AUC between the comprehensive model and CECT (Z=-0.252, P=0.801). Both in the internal and external validation cohort, the Calibration Curve and Decision Curve Analysis showed a better performance of the comprehensive model. Conclusion: It is feasible to construct an ultrasonographic radiomics model for distinguishing small ccRCC and RAML based on ultrasound images, and the diagnostic performance of the comprehensive model is superior to the clinical ultrasound imaging model and ultrasonographic radiomics model, similar to that of CECT.
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We undertook a survey among epileptologists in China to explore their attitudes toward physical exercise and sports for persons with epilepsy (PWEs). A total of 288 epileptologists participated. Most recognized the potential benefits of physical exercise and sports for PWEs, including improved cognitive function (74.6 %), alleviation of mental disorders (73.2 %), and enhanced quality of life (83.8 %). Epileptologists overwhelmingly agreed on the importance of discussing and encouraging physical exercise and sports for PWEs (97.4 % and 95.2 %, respectively). Before engagement in physical exercise and sports, most epileptologists considered that the duration of seizure-free status could be shorter if the seizures were typically focal, non-motor, or without impaired awareness (p < 0.05). There was consensus (99.1 %) on the need to grade the risk of related activities. Opinions were divided regarding the use of health certificates for restricting PWEs (favored by 63.2 %). The majority (93.9 %) called for an expert consensus or clinical guidelines in China. In conclusion, epileptologists in China generally demonstrate a positive attitude toward physical exercise and sports for PWEs. Both benefits and risks of these activities have generally been acknowledged. It is recommended to prioritize activities with lower risks and higher benefits. However, the recommendations for PWEs with a lower likelihood of recurrence and less risky seizure types can be more liberal. Urgent development of normative guidance from governmental and professional bodies is warranted.
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Transgenerational gene expression depends on both underlying DNA sequences and epigenetic modifications. The latter, which can result in transmission of variegated gene expression patterns across multiple generations without DNA alterations, has been termed epigenetic inheritance and has been documented in plants, worms, flies and mammals. Whereas transcription factors binding to cognate DNA sequence elements regulate gene expression, the molecular basis for epigenetic inheritance has been linked to histone and DNA modifications and non-coding RNA. Here we report that mutation of the CCAAT box promoter element abrogates NF-Y binding and disrupts the stable transgenerational expression of an MHC class I transgene. Transgenic mice with a mutated CCAAT box in the MHC class I transgene display variegated expression of the transgene among littermates and progeny in multiple independently derived transgenic lines. After 4 generations, CCAAT mutant transgenic lines derived from a single founder stably displayed distinct patterns of expression. Histone modifications and RNA polymerase II binding correlate with expression of CCAAT mutant transgenic lines, whereas DNA methylation and nucleosome occupancy do not. Mutation of the CCAAT box also results in changes to CTCF binding and DNA looping patterns across the transgene that correlate with expression status. These studies identify the CCAAT promoter element as a regulator of stable transgenerational gene expression such that mutation of the CCAAT box results in variegated transgenerational inheritance. Considering that the CCAAT box is present in 30% of eukaryotic promoters, this study provides insights into how fidelity of gene expression patterns is maintained through multiple generations.
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Ratones Transgénicos , Regiones Promotoras Genéticas , Animales , Ratones , Metilación de ADN , Epigénesis Genética , Factor de Unión a CCAAT/genética , Factor de Unión a CCAAT/metabolismo , Regulación de la Expresión Génica , Genes MHC Clase I , Mutación , Histonas/metabolismo , Histonas/genética , ARN Polimerasa II/metabolismo , ARN Polimerasa II/genética , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Transgenes , Nucleosomas/metabolismo , Nucleosomas/genéticaRESUMEN
OBJECTIVE: Previous research on diagnostic assessment by superb microvascular imaging (SMI) were based on qualitative or semi-quantitative assessments of vascularity, which may be subjective and unrepeatable by different sonographers. This study aimed to evaluate diagnostic performance of SMI Image-pro Plus (IPP) based vascular index (VI) for malignant renal masses. METHOD: We retrospectively reviewed 222 masses in 214 patients who underwent SMI between August 2019 and August 2022 in our study. We evaluated the diagnostic performance of blood flow via Alder grade, VI based on both IPP and SMI. RESULTS: The kappa consistency of the Adler grade and VI for renal masses was classified among different observers were 0.765 and 0.824. The intra-observers correlation ecoefficiency (ICC) were 0.727 and 0.874. Benign renal masses were mainly Adler grade 0, grade I, and grade II, VI was 4.30 ± 4.27 (Range 0.98-16.42); while malignant masses were mainly Adler grade III, VI was 14.95 ± 10.94 (Range 0.79-56.89). VI was higher in malignant than benign masses (tâ¯=â¯15.638, P < 0.01). Among the malignant masses, the mean VI in clear cell renal cell carcinoma was higher than that in papillary renal cell carcinoma and chromophobe renal cell carcinoma (Fâ¯=â¯30.659, P < 0.01). The sensitivity, specificity and accuracy of SMI were 80.00%, 71.15%, and 78.64%, respectively. The sensitivity, specificity, and accuracy were 60.59%, 88.46%, and 80.18% by using a VI of 7.95 as the cutoff value to identify malignant lesions from benign masses yielded. VI had better diagnostic efficiency than ultrasonic characteristics and Adler grade in benign and malignant differential diagnosis (Zâ¯=â¯4.851, P < 0.01; Zâ¯=â¯2.732, P < 0.01). CONCLUSION: VI was higher in malignant than benign in renal masses. In malignant masses, VI in CCRCC was higher than that in papillary renal cell carcinoma and ChRCC. As a noninvasive examination, it had important clinical significance in the differential diagnosis of renal masses. VI from IPP may assist sonographer in distinguish renal malignances as a quantitative tool for vascularity.
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Neoplasias Renales , Microvasos , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/diagnóstico , Femenino , Masculino , Diagnóstico Diferencial , Estudios Retrospectivos , Persona de Mediana Edad , Microvasos/diagnóstico por imagen , Microvasos/patología , Anciano , Adulto , Anciano de 80 o más Años , Adulto JovenRESUMEN
BACKGROUND: Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis. AIM: To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM. METHODS: Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed. RESULTS: A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis. CONCLUSION: Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors.
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Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.
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Puntos de Acupuntura , Presión Sanguínea , Hipertensión , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Hipertensión/terapia , Hipertensión/fisiopatologíaRESUMEN
Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.
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Colorantes Fluorescentes , Tiadiazoles , Vino , Frutas , ProtonesRESUMEN
SLC25A51 selectively imports oxidized NAD+ into the mitochondrial matrix and is required for sustaining cell respiration. We observed elevated expression of SLC25A51 that correlated with poorer outcomes in patients with acute myeloid leukemia (AML), and we sought to determine the role SLC25A51 may serve in this disease. We found that lowering SLC25A51 levels led to increased apoptosis and prolonged survival in orthotopic xenograft models. Metabolic flux analyses indicated that depletion of SLC25A51 shunted flux away from mitochondrial oxidative pathways, notably without increased glycolytic flux. Depletion of SLC25A51 combined with 5-azacytidine treatment limits expansion of AML cells in vivo. Together, the data indicate that AML cells upregulate SLC25A51 to decouple mitochondrial NAD+/NADH for a proliferative advantage by supporting oxidative reactions from a variety of fuels. Thus, SLC25A51 represents a critical regulator that can be exploited by cancer cells and may be a vulnerability for refractory AML.
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Leucemia Mieloide Aguda , NAD , Humanos , Línea Celular Tumoral , Proliferación Celular , Leucemia Mieloide Aguda/metabolismo , Mitocondrias/metabolismo , NAD/metabolismo , Oxidación-ReducciónRESUMEN
OBJECTIVES: Epilepsy care in China has expanded considerably in the last decade but still remains largely unknown; we developed an easy-to-use tool to assess its quality. METHODS: We adapted the Epilepsy Update Quality Measurement, produced by the American Academy of Neurology (AAN) for use in China: The Quality Indicator for Epilepsy Treatment-China National Action (QUIET-CHINA). This tool incorporates a standardized case report form initially for logging quality indicators for people with epilepsy during in-patient stays. Nine quality indicators covered seizures, drugs, diagnostics, screening for co-morbid conditions, counseling for woman of child bearing age, and a composite indicator was further proposed by total number of interventions performed divided by the total number of people eligible in each indicator. The tool also has an electronic reporting and data feedback system. 96 epilepsy centers in 31 jurisdictions in mainland China have been piloted since 2017. RESULTS: Data from 11,600 individuals with epilepsy in the first 3-year study period were analyzed. The median age was 31; 60% were male. The composite indicators were 74%. Seizure freedom rate was less than 25% in all epilepsy types and post-surgical seizure freedom rate was 21%. 90% had seizure type and frequency, antiepileptic drugs recorded, while only 70% with active epilepsy were on regular antiepileptic drugs treatment. Investigations for diagnosis and etiology were performed in around 90% but screening for co-morbid conditions and counseling for women of childbearing potential was 38% and 15% respectively. Severe side effect happened in 2% individuals during the treatment. CONCLUSION: The preliminary results of the national action provided some baseline information. Except for an overall improvement, a significant treatment gap still exists, and psychiatric co-morbidities or issues affecting women are not seen as a priority. QUIET-CHINA will be expanded to more and other levels of hospitals, to help narrow the treatment gap and equalize the comprehensive epilepsy care on the national level.
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Anticonvulsivantes , Epilepsia , Masculino , Femenino , Humanos , Adulto , Anticonvulsivantes/uso terapéutico , Indicadores de Calidad de la Atención de Salud , Epilepsia/diagnóstico , Epilepsia/terapia , Epilepsia/inducido químicamente , Convulsiones/tratamiento farmacológico , ChinaRESUMEN
Practical applications of synthetic self-propelled nano and microparticles for microrobotics, targeted drug delivery, and manipulation at the nanoscale are rapidly expanding. However, fabrication limitations often hinder progress, resulting in relatively simple shapes and limited functionality. Here, taking advantage of 3D nanoscale printing, chiral micropropellers powered by the hydrogen peroxide reduction reaction are fabricated. Due to their chirality, the propellers exhibit multifunctional behavior controlled by an applied magnetic field: spinning in place (loitering), directed migration in the prescribed direction, capture, and transport of polymer cargo particles. Design parameters of the propellers are optimized by computation modeling based on mesoscale molecular dynamics. It is predicted by computer simulations, and confirmed experimentally, that clockwise rotating propellers attract each other and counterclockwise repel. These results shed light on how chirality and shape optimization enhance the functionality of synthetic autonomous micromachines.
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Objective: To review research advances of revision surgery after primary total hip arthroplasty (THA) for patients with Crowe type â £ developmental dysplasia of the hip (DDH). Methods: The recent literature on revision surgery after primary THA in patients with Crowe type â £ DDH was reviewed. The reasons for revision surgery were analyzed and the difficulties of revision surgery, the management methods, and the related prosthesis choices were summarized. Results: Patients with Crowe type â £ DDH have small anteroposterior diameter of the acetabulum, large variation in acetabular and femoral anteversion angles, severe soft tissue contractures, which make both THA and revision surgery more difficult. There are many reasons for patients undergoing revision surgery after primary THA, mainly due to aseptic loosening of the prosthesis. Therefore, it is necessary to restore anatomical structures in primary THA, as much as possible and reduce the generation of wear particles to avoid postoperative loosening of the prosthesis. Due to the anatomical characteristics of Crowe type â £ DDH, the patients have acetabular and femoral bone defects, and the repair and reconstruction of bone defects become the key to revision surgery. The acetabular side is usually reconstructed with the appropriate acetabular cup or combined metal block, Cage, or custom component depending on the extent of the bone defect, while the femoral side is preferred to the S-ROM prosthesis. In addition, the prosthetic interface should be ceramic-ceramic or ceramic-highly cross-linked polyethylene wherever possible. Conclusion: The reasons leading to revision surgery after primary THA in patients with Crowe type â £ DDH and the surgical difficulties have been clarified, and a large number of clinical studies have proposed corresponding revision modalities based on which good early- and mid-term outcomes have been obtained, but further follow-up is needed to clarify the long-term outcomes. With technological advances and the development of new materials, personalized prostheses for these patients are expected to become a reality.
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Artroplastia de Reemplazo de Cadera , Displasia del Desarrollo de la Cadera , Luxación Congénita de la Cadera , Prótesis de Cadera , Humanos , Acetábulo/cirugía , Artroplastia de Reemplazo de Cadera/métodos , Displasia del Desarrollo de la Cadera/cirugía , Luxación Congénita de la Cadera/cirugía , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) and stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) are two effective, minimally invasive treatments for epilepsy with focal cortical dysplasia (FCD). The purpose of this study is to conduct a meta-analysis to evaluate and compare the efficacy and safety of these two therapies in epilepsy patients with FCD. Methods: We searched PubMed, Embase, Cochrane, and other databases for articles published before March 2023. The primary objective was to compare the effectiveness and complications of MRgLiTT and SEEG-RFTC in epilepsy patients with FCD. The second objective was to determine which method provides a better prognosis for specific subgroup patients. Results: According to the inclusion and exclusion criteria, 18 studies were included, comprising 270 FCD patients including 37 patients from 6 MRgLiTT studies and 233 from 12 SEEG-RFTC studies. There were no significant differences between MRgLiTT and SEEG-RFTC groups in the seizure-freedom rate (59%, 95% CI 44-74%; 52%, 95% CI 47-57%, P = 0.86) and the rate of ≥50% seizure-reduction of FCD (90%, 95% CI 80-100%; 90%, 95% CI 86-94%, P = 0.42). Both methods had low complication rates (17.1%, 28/159) and long-term complication (2.5%, 4/159) rate, with no significant difference between them (P = 0.17). Conclusion: Both MRgLiTT and SEEG-RFTC are safe and minimally invasive treatments for patients with FCD. They have comparable performance in terms of postoperative seizure-freedom rates in patients with FCD, and both can be used as treatment options for patients with FCD. Our study found that SEEG-RFTC had a better therapeutic effect in the FCD2b subgroup.
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In a stretcher, the surface distortion of the optical elements can introduce spectral phase modulations into the laser, which can affect the laser's signal-to-noise ratio. In this paper, by combining ray tracing methods and angular spectrum diffraction methods, the impact of the mid-frequency surface distortion of the optical elements in an cylindrical Offner stretcher on the far-field signal-to-noise ratio of the laser is simulated. The results show that reducing the spatial chirp on the convex cylindrical mirror can effectively improve the far-field signal-to-noise ratio of the laser, and two methods to improve the far-field signal-to-noise ratio are presented.
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Advances in single-cell sequencing and data analysis have made it possible to infer biological trajectories spanning heterogeneous cell populations based on transcriptome variation. These trajectories yield a wealth of novel insights into dynamic processes such as development and differentiation. However, trajectory analysis relies on an assumption of trajectory continuity, and experimental limitations preclude some real-world scenarios from meeting this condition. The current lack of assessment metrics makes it difficult to ascertain if/when a given trajectory deviates from continuity, and what impact such a divergence would have on inference accuracy is unclear. By analyzing simulated breaks introduced into in silico and real single-cell data, we found that discontinuity caused precipitous drops in the accuracy of trajectory inference. We then generate a simple scoring algorithm for assessing trajectory continuity, and found that continuity assessments in real-world cases of intestinal stem cell development and CD8 + T cells differentiation efficiently identifies trajectories consistent with empirical knowledge. This assessment approach can also be used in cases where a priori knowledge is lacking to screen a pool of inferred lineages for their adherence to presumed continuity, and serve as a means for weighing higher likelihood trajectories for validation via empirical studies, as exemplified by our case studies in psoriatic arthritis and acute kidney injury. This tool is freely available through github at qingshanni/scEGRET.
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Algoritmos , Transcriptoma , Diferenciación Celular , Análisis de la Célula IndividualRESUMEN
OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.
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Terapia por Acupuntura , Accidente Cerebrovascular , Ratas , Masculino , Animales , Espasticidad Muscular/etiología , Espasticidad Muscular/terapia , Ratas Sprague-Dawley , Cuero Cabelludo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Infarto CerebralRESUMEN
In the context of global climate change and the influence of human activities, the concept of "sponge city" is put forward to realize the purification, collection, and reuse of rainwater. The effective evaluation of LID facilities in sponge cities is of great guiding significance for the promotion and construction of sponge cities. IFMS (Integrated Flood Modeling System) Urban was selected to construct the rainstorm simulation. LID parameters were added to simulate the improvement of urban waterlogging after the construction of sponge city. A reasonable disaster loss assessment method was used to calculate the disaster mitigation benefit brought by the construction of sponge city. Through the comparison of the inundation situation before and after LID facilities' construction, it can be concluded that the mitigation effect of LID facilities on the overall inundation area of the city decreases with the increase of rainfall recurrence period, with the maximum reduction rate reaching 13.63% in the 5-year recurrence period and the minimum reduction rate of 11.06% in the 50-year recurrence period. LID facilities have a better disaster reduction effect for rainfall events with a small recurrence period than for rainfall events with a large recurrence period.
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BACKGROUND: Most physicians consider molars with chronic apical periodontitis (CAP) lesions as contraindications for immediate implant placement. At the patient's request, we perform immediate implant placement of the mandibular molars with CAP in clinical practice. AIM: To retrospectively analyze and compare the 5-year outcomes of immediate implant placement of the mandibular molars with CAP and those without obvious inflammation. METHODS: The clinical data of patients with immediate implant placement of the mandibular molars in the Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, from June 2015 to June 2017 were collected. The patients were divided into CAP (n = 52) and no-CAP (n = 45) groups. Changes in bone mineral density and bone mass around implants were analyzed 5 years after implant restoration. RESULTS: At 5 years after implantation, the peri-implant bone mineral density was 528.2 ± 78.8 Hounsfield unit (HU) in the CAP group and 562.6 ± 82.9 HU in the no-CAP group (P = 0.126). Marginal bone resorption around implants did not differ significantly between the two groups, including buccal (P = 0.268) or lingual (P = 0.526) resorption in the vertical direction or buccal (P = 0.428) or lingual (P = 0.560) resorption in the horizontal direction. Changes in the peri-implant jump space did not differ significantly between the two groups, including the buccal (P = 0.247) or lingual (P = 0.604) space in the vertical direction or buccal (P = 0.527) or lingual (P = 0.707) space in the horizontal direction. The gray value of cone-beam computed tomography measured using Image J software can reflect the bone mineral density. In the CAP area, the gray values of the bone tissue immediately and 5 years after implant placement differed significantly from those of the surrounding bone tissue (P < 0.01). CONCLUSION: The results of this study suggest that immediate implant placement of the mandibular molars with CAP can achieve satisfactory 5-year clinical results, without significant differences in the complications, survival rate, or bone tissue condition from the no-CAP mandibular molars.
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SLC25A51 is a member of the mitochondrial carrier family (MCF) but lacks key residues that contribute to the mechanism of other nucleotide MCF transporters. Thus, how SLC25A51 transports NAD+ across the inner mitochondrial membrane remains unclear. To elucidate its mechanism, we use Molecular Dynamics simulations to reconstitute SLC25A51 homology models into lipid bilayers and to generate hypotheses to test. We observe spontaneous binding of cardiolipin phospholipids to three distinct sites on the exterior of SLC25A51's central pore and find that mutation of these sites impairs cardiolipin binding and transporter activity. We also observe that stable formation of the required matrix gate is controlled by a single salt bridge. We identify binding sites in SLC25A51 for NAD+ and show that its selectivity for NAD+ is guided by an electrostatic interaction between the charged nicotinamide ring in the ligand and a negatively charged patch in the pore. In turn, interaction of NAD+ with interior residue E132 guides the ligand to dynamically engage and weaken the salt bridge gate, representing a ligand-induced initiation of transport.
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Cardiolipinas , NAD , Cardiolipinas/metabolismo , Ligandos , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , HumanosRESUMEN
BACKGROUND: The differentiation of pericytes into myofibroblasts causes microvascular degeneration, ECM (extracellular matrix) accumulation, and tissue stiffening, characteristics of fibrotic diseases. It is unclear how pericyte-myofibroblast differentiation is regulated in the microvascular environment. Our previous study established a novel 2-dimensional platform for coculturing microvascular endothelial cells (ECs) and pericytes derived from the same tissue. This study investigated how ECM stiffness regulated microvascular ECs, pericytes, and their interactions. METHODS: Primary microvessels were cultured in the TGM2D medium (tubular microvascular growth medium on 2-dimensional substrates). Stiff ECM was prepared by incubating ECM solution in regular culture dishes for 1 hour followed by PBS wash. Soft ECM with Young modulus of ≈6 kPa was used unless otherwise noted. Bone grafts were prepared from the rat skull. Immunostaining, RNA sequencing, RT-qPCR (real-time quantitative polymerase chain reaction), Western blotting, and knockdown experiments were performed on the cells. RESULTS: Primary microvascular pericytes differentiated into myofibroblasts (NG2+αSMA+) on stiff ECM, even with the TGFß (transforming growth factor beta) signaling inhibitor A83-01. Soft ECM and A83-01 cooperatively maintained microvascular stability while inhibiting pericyte-myofibroblast differentiation (NG2+αSMA-/low). We thus defined 2 pericyte subpopulations: primary (NG2+αSMA-/low) and activated (NG2+αSMA+) pericytes. Soft ECM promoted microvascular regeneration and inhibited fibrosis in bone graft transplantation in vivo. As integrins are the major mechanosensor, we performed RT-qPCR screening of integrin family members and found Itgb1 (integrin ß1) was the major subunit downregulated by soft ECM and A83-01 treatment. Knocking down Itgb1 suppressed myofibroblast differentiation on stiff ECM. Interestingly, ITGB1 phosphorylation (Y783) was mainly located on microvascular ECs on stiff ECM, which promoted EC secretion of paracrine factors, including CTGF (connective tissue growth factor), to induce pericyte-myofibroblast differentiation. CTGF knockdown or monoclonal antibody treatment partially reduced myofibroblast differentiation, implying the participation of multiple pathways in fibrosis formation. CONCLUSIONS: ECM stiffness and TGFß signaling cooperatively regulate microvascular stability and pericyte-myofibroblast differentiation. Stiff ECM promotes EC ITGB1 phosphorylation (Y783) and CTGF secretion, which induces pericyte-myofibroblast differentiation.
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Comunicación Paracrina , Pericitos , Ratas , Animales , Pericitos/metabolismo , Células Endoteliales/metabolismo , Células Cultivadas , Factor de Crecimiento Transformador beta/metabolismo , Fibrosis , Matriz Extracelular/metabolismo , Miofibroblastos/metabolismoRESUMEN
Background: Observational studies have shown that anti-tumor necrosis factor (TNF) therapy may be beneficial for patients with coronavirus disease 2019 (COVID-19). Nevertheless, because of the methodological restrictions of traditional observational studies, it is a challenge to make causal inferences. This study involved a two-sample Mendelian randomization analysis to investigate the causal link between nine TNFs and COVID-19 severity using publicly released genome-wide association study summary statistics. Methods: Summary statistics for nine TNFs (21,758 cases) were obtained from a large-scale genome-wide association study. Correlation data between single-nucleotide polymorphisms and severe COVID-19 (18,152 cases vs. 1,145,546 controls) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by inverse variance-weighted (IVW), MR-Egger, and weighted median methods. Sensitivity tests were conducted to assess the validity of the causal relationship. Results: Genetically predicted TNF receptor superfamily member 6 (FAS) positively correlated with the severity of COVID-19 (IVW, odds ratio = 1.10, 95% confidence interval = 1.01-1.19, p = 0.026), whereas TNF receptor superfamily member 5 (CD40) was protective against severe COVID-19 (IVW, odds ratio = 0.92, 95% confidence interval = 0.87-0.97, p = 0.002). Conclusion: Genetic evidence from this study supports that the increased expression of FAS is associated with the risk of severe COVID-19 and that CD40 may have a potential protective effect against COVID-19.