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BACKGROUND AND PURPOSE: The relationship between heart rate and the prognosis of patients with large vessel occlusion strokes treated with mechanical thrombectomy (MT) is not well established. This study aimed to evaluate the association of mean heart rate and heart rate variability (HRV) with the clinical outcomes after MT therapy. METHODS: Acute ischemic stroke patients undergoing MT therapy were prospectively recruited from March 2020 to November 2022. Their heart rate was collected every hour for the initial 72 h after MT procedure, and the variability of heart rate was measured by standard deviation (SD) and coefficient of variation (CV). All-cause mortality and worsening of functional outcome (change in modified Rankin Scale (mRS) score) at 3-month were captured. Binary logistic regression was used to evaluate the association between heart rate indicators and all-cause mortality. Ordinal logistic regression was used to evaluate the association between heart rate indicators and worsening of functional outcome. RESULTS: Among 191 MT-treated patients, 51(26.7%) patients died at 3-month after stroke. Increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were all associated with the increased risk of mortality (adjusted hazard ratio [aHR] with 95% CI: 1.29 [1.09-1.51], 1.19 [1.07-1.32], 1.14 [1.03-1.27]; respectively). Patients in the highest tertile of heart rate SD had an increased risk of mortality (4.62, 1.70-12.52). After using mRS as a continuous variable, we found increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were associated with the worsening of functional outcome (adjusted odds ratio [aOR] with 95% CI: 1.35 [1.11-1.64], 1.27 [1.05-1.53], 1.19 [1.02-1.40]; respectively). A linear relationship was observed between mean heart rate or heart rate SD and mortality; while all of the heart rate measures in this study showed a linear relationship with the worsening of functional outcome. CONCLUSIONS: Higher mean heart rate and HRV were associated with the increased risk of 3-month all-cause mortality and worse functional outcome after MT therapy for AIS patients.
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Frecuencia Cardíaca , Accidente Cerebrovascular Isquémico , Trombectomía , Humanos , Masculino , Femenino , Anciano , Frecuencia Cardíaca/fisiología , Persona de Mediana Edad , Trombectomía/métodos , Trombectomía/estadística & datos numéricos , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/fisiopatología , Resultado del Tratamiento , Anciano de 80 o más Años , Estudios Prospectivos , Pronóstico , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor that originates in the nasopharyngeal mucosa and is common in China and Southeast Asian countries. Cancer cells reprogram glycolytic metabolism to promote their growth, survival and metastasis. Glycolysis plays an important role in NPC development, but the underlying mechanisms remain incompletely elucidated. Lactate dehydrogenase A (LDHA) is a crucial glycolytic enzyme, catalyzing the last step of glycolysis. This study aims to investigate the exact role of LDHA, which catalyzes the conversion of pyruvate into lactate, in NPC development. METHODS AND RESULTS: The western blot and immunohistochemical (IHC) results indicated that LDHA was significantly upregulated in NPC cells and clinical samples. LDHA knockdown by shRNA significantly inhibited NPC cell proliferation and invasion. Further knockdown of LDHA dramatically weakened the tumorigenicity of NPC cells in vivo. Mechanistic studies showed that LDHA activated TGF-ß-activated kinase 1 (TAK1) and subsequent nuclear factor κB (NF-κB) signaling to promote NPC cell proliferation and invasion. Exogenous lactate supplementation restored NPC cell proliferation and invasion inhibited by LDHA knockdown, and this restorative effect was reversed by NF-κB inhibitor (BAY 11-7082) or TAK1 inhibitor (5Z-7-oxozeaenol) treatment. Moreover, clinical sample analyses showed that LDHA expression was positively correlated with TAK1 Thr187 phosphorylation and poor prognosis. CONCLUSIONS: Our results suggest that LDHA and its major metabolite lactate drive NPC progression by regulating TAK1 and its downstream NF-κB signaling, which could become a therapeutic target in NPC.
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Lactato Deshidrogenasa 5 , Quinasas Quinasa Quinasa PAM , FN-kappa B , Neoplasias Nasofaríngeas , Humanos , Lactato Deshidrogenasa 5/genética , Ácido Láctico , Quinasas Quinasa Quinasa PAM/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , FN-kappa B/metabolismoRESUMEN
Emerging findings point to a role for C1q/TNF-related protein 4 (CTRP4) in feeding in mammals. However, it remains unknown whether CTRP4 regulates feeding in fish. This study aimed to determine the feeding regulation function of CTRP4 in Siberian sturgeon (Acipenser baerii). In this study, the Siberian sturgeon ctrp4 (Abctrp4) gene was cloned, and Abctrp4 mRNA was shown to be highly expressed in the hypothalamus. In the hypothalamus, Abctrp4 mRNA decreased during fasting and reversed after refeeding. Subsequently, we obtained the AbCTRP4 recombinant protein by prokaryotic expression and optimized the expression and purification conditions. Siberian sturgeon (81.28 ± 14.75 g) were injected intraperitoneally using 30, 100, and 300 ng/g Body weight (BW) AbCTRP4 to investigate its effect on feeding. The results showed that 30, 100, and 300 ng/g BW of the AbCTRP4 significantly reduced the cumulative food intake of Siberian sturgeon at 1, 3, and 6 h. Finally, to investigate the potential mechanism of CTRP4 feeding inhibition, 300 ng/g BW AbCTRP4 was injected intraperitoneally. The findings demonstrated that AbCTRP4 treatment for 1 h significantly promoted the mRNA levels of anorexigenic peptides (pomc, cart, and leptin) while suppressing the mRNA abundances of orexigenic peptides (npy and agrp).In addition, the jak2/stat3 pathway in the hypothalamus was significantly activated after 1 h of AbCTRP4 treatment. In conclusion., this study confirms the anorexigenic effect of CTRP4 in Siberian sturgeon.
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Apetito , Complemento C1q , Animales , Apetito/genética , Complemento C1q/metabolismo , Complemento C1q/farmacología , Ingestión de Alimentos/fisiología , Peces/fisiología , Péptidos/genética , Péptidos/farmacología , Péptidos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Mamíferos/metabolismoRESUMEN
Objective: This study aimed to search and analyze relevant evidence on perioperative activities in patients undergoing hepatectomy and provide a summary of the best evidence available. Methods: Comprehensive computer searches were conducted in various databases, including PubMed, Cochrane Library, BMJ Best Practice, Joanna Briggs Institute, Evidence-Based Health Care Centre Database, US Guidelines Network, UK National Institute of Clinical Medicine, Scottish Intercollegiate Guidelines Network, International Guidelines Association Network, New Zealand Clinical Practice Guidelines Network, and Chinese Biomedical Literature Database from January 30, 2022 to December 30, 2023. The search included guidelines, expert consensus, evidence summaries, systematic reviews, and original research closely related to the evidence. Results: A total of 11 pieces of evidence were included, consisting of 2 guidelines, 2 expert consensuses, 1 evidence summary, 1 systematic review, and 5 randomized controlled trials (RCTs). From these, five pieces of best evidence were identified. Conclusions: The evidence from the included studies collectively indicates that well-planned perioperative activities are safe and beneficial for patients undergoing hepatectomy. Furthermore, high-quality local guidelines have been established in China, suggesting that healthcare professionals can adopt these practices to accelerate patient recovery and enhance the quality of clinical care.
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Periodontitis is a highly prevalent disease that damages the supporting tissues of a tooth, including the alveolar bone. Alveolar bone loss owing to periodontitis is broadly categorized as supra-alveolar and intra-alveolar bone loss. In intra-alveolar bone loss, the defect has an angular or oblique orientation to the long axis of the tooth in an apical direction. In contrast, the defect is perpendicular to the long axis of the tooth in supra-alveolar bone loss. Unlike intra-alveolar bone defects, supra-alveolar bone defects lack supporting adjacent space, which makes supra-alveolar bone regeneration more challenging. In addition, the limited availability of resources in terms of vascularity and underlying tissues is another obstacle to supra-alveolar bone regeneration. Currently, supra-alveolar bone loss is the least predictable periodontal defect type in regenerative periodontal therapy. In addition, supra-alveolar bone loss is much more common than other alveolar bone loss. Despite its prevalence, research on supra-alveolar bone regeneration remains sparse, indicating an unmet need for significant research efforts in this area. This review summarize recent advances, obstacles, and future directions in the field of supra-alveolar bone regeneration. We discuss the biomaterials, bioactive molecules, and cells that have been tested for supra-alveolar bone regeneration, followed by pre-clinical and clinical approaches employed in this field. Additionally, we highlight obstacles and present future directions that will propel supra-alveolar bone research forward.
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A rare case of trigeminal neuralgia following injections of Hyaluronic Acid and Botox was documented. In addressing the severe pain and swelling caused by the injection, a novel combination therapy was employed, notably including 5-fluorouracil. The significant improvement observed in this case not only provided clinical insights but also spurred further investigation into the underlying mechanisms linking trigeminal nerve damage to local dermal filler injections. The aim was to glean new medical perspectives and develop practical preventive strategies to mitigate such complications in future cases. This approach highlights the importance of understanding and addressing the potential neurological impacts of cosmetic procedures. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .
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Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon.
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Peces , Gastrinas , Receptor de Colecistoquinina B , Animales , Gastrinas/metabolismo , Peces/fisiología , Peces/metabolismo , Receptor de Colecistoquinina B/metabolismo , Receptor de Colecistoquinina B/genética , Conducta Alimentaria/efectos de los fármacos , ARN Mensajero/metabolismo , ARN Mensajero/genética , Hipotálamo/metabolismoRESUMEN
The space-based gravitational wave detection mission, TianQin, requires high-level synchronization between independent clocks of all spacecrafts to extract the gravitational wave signals. It is necessary to measure the inter-spacecraft relative clock jitter based on laser phase-sideband clock transfer. The main challenge is the tracking and locking of clock sideband beatnote signals with low signal-to-noise ratio and frequency variation. In this paper, a systematic scheme of inter-spacecraft clock jitter readout is reported. The requirement of the clock transfer link for TianQin based on the time-delay interferometry algorithm is derived. A bi-directional laser interferometer system with a transmission optical power below 1 nW and a time delay of â¼50 µs is built up to demonstrate the weak-light clock transfer. In this scheme, frequency modulation is performed on the laser to simulate the inter-spacecraft Doppler frequency shift and its variation. Based on electrical and optical clock transfer comparison experiments, it is demonstrated that the GHz frequency synthesizer is the main noise source below the 50â mHz frequency range. The residual clock jitter noise introduced by the optical transfer link is below 40 fs/Hz1/2 above the 6â mHz frequency range, and the fractional frequency instability is less than 6.7 × 10-17 at 1000 s, which meets the requirement of the TianQin mission. Ultimately, The carrier phase measurement accuracy reaches 1 × 10-4 cycles/Hz1/2 above 6â mHz after differential clock noise correction using measured clock jitter.
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BACKGROUND AND AIMS: Measuring adenoma detection rates (ADRs) at the population level is challenging because pathology reports are often reported in an unstructured format; further, there is significant variation in reporting methods across institutions. Natural language processing (NLP) can be used to extract relevant information from text-based records. We aimed to develop and validate an NLP algorithm to identify colorectal adenomas that could be used to report ADR at the population level in Ontario, Canada. METHODS: The sampling frame included pathology reports from all colonoscopies performed in Ontario in 2015 and 2016. Two random samples of 450 and 1000 reports were selected as the training and validation sets, respectively. Expert clinicians reviewed and classified reports as adenoma or other. The training set was used to develop an NLP algorithm (to identify adenomas) that was evaluated using the validation set. The NLP algorithm test characteristics were calculated using expert review as the reference. We used the algorithm to measure ADR for all endoscopists in Ontario in 2019. RESULTS: The 1450 pathology reports were derived from 62 laboratories, 266 pathologists, and 532 endoscopists. In the training set, the NLP algorithm for any adenoma had a sensitivity of 99.60% (95% confidence interval (CI), 97.77-99.99), specificity of 99.01% (95% CI, 96.49-99.88), positive predictive value of 99.19% (95% CI, 97.12-99.90), and F1 score of .99. Similar results were obtained for the validation set. The median ADR was 33% (interquartile range, 26%-40%). CONCLUSIONS: When we used a population-based sample from Ontario, our NLP algorithm was highly accurate and was used at the system level to measure ADR.
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Adenoma , Procesamiento de Lenguaje Natural , Humanos , Adenoma/diagnóstico , Colonoscopía/métodos , Algoritmos , OntarioRESUMEN
Neuromedin U (NMU) has a critical function on the regulation of food intake in mammals, while the information is little in teleost. To investigate the function of NMU on appetite regulation of Siberian sturgeon (Acipenser baerii), this study first cloned nmu cDNA sequence that encoded 154 amino acids including NMU-25 peptide. Besides, the results showed that nmu mRNA was widely distributed in various tissues especially in the hypothalamus and telencephalon. The results of nutritional status (pre-feeding and post-feeding, fasting and re-feeding) experiments showed that nmu mRNA expression was significantly decreased at 1 and 3 h after feeding in different brain regions. Similarly, after feeding, the expression of nmu significantly decreased in peripheral tissues. Moreover, nmu expression in the hypothalamus was significantly increased after fasting 1 d, but decreased after fasting 17 d, which was significantly reversed after re-feeding. However, other brain regions like telencephalon and peripheral tissues like oesophagus, intestinum valvula and liver have different change patterns. Further study showed that acute i.c.v. and i.p. injection of NMU and chronic i.p. injection of NMU significantly reduced the food intake in a dose-dependent mode. In addition, the expressions of several critical appetite factors (nmu, aplein, cart, cck, ghrelin, npy, nucb2, pyy and ucn3) were significantly affected by acute NMU-25 administration in the hypothalamus, intestinum valvula and liver. These results indicate that NMU-25 has the anorexigenic function on food intake by affecting different appetite factors in Siberian sturgeon, which provides a foundation for further exploring the appetite regulation networks in fish.
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Apetito , Ingestión de Alimentos , Animales , Apetito/fisiología , Ingestión de Alimentos/genética , Peces/metabolismo , ARN Mensajero/metabolismo , Mamíferos/genética , Mamíferos/metabolismoRESUMEN
OBJECTIVES: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED). METHODS: Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022. RESULTS: One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58. CONCLUSIONS: IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.
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Degeneración Macular , Desprendimiento de Retina , Humanos , Ranibizumab/uso terapéutico , Inhibidores de la Angiogénesis/uso terapéutico , Desprendimiento de Retina/tratamiento farmacológico , Metaanálisis en Red , Factor A de Crecimiento Endotelial Vascular , Epitelio Pigmentado de la Retina , Estudios Retrospectivos , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológicoRESUMEN
Quartz tuning forks (QTFs) are self-sensing and possess a high quality factor, allowing them to be used as probes for atomic force microscopes (AFMs) for which they offer nano-scale resolution of sample images. Since recent work has revealed that utilizing higher-order modes of QTFs can offer better resolution of AFM images and more information on samples, it is necessary to understand the relationship between the vibration characteristics of the first two symmetric eigenmodes of quartz-based probes. In this paper, a model that combines the mechanical and electrical characteristics of the first two symmetric eigenmodes of a QTF is presented. Firstly, the relationships between the resonant frequency, amplitude, and quality factor between the first two symmetric eigenmodes are theoretically derived. Then, a finite element analysis is conducted to estimate the dynamic behaviors of the analyzed QTF. Finally, experimental tests are executed to verify the validity of the proposed model. The results indicate that the proposed model can accurately describe the dynamic properties of a QTF in the first two symmetric eigenmodes either under electrical or mechanical excitation, which will provide a reference for the description of the relationship between the electrical and mechanical responses of the QTF probe in the first two symmetric eigenmodes as well as the optimization of higher modal responses of the QTF sensor.
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Previous data suggested that activation of endocannabinoid receptor 1 (CB1) was necessary for the orexigenic effect of Ghrelin in rodents, but the information is limited in teleosts. To investigate the feeding regulation pathway of Ghrelin and CB1 in Siberian sturgeon (Acipenser baerii), this study first identified the Ghrelin (345 bp, complete coding sequence) and Ghrelin receptor (GHSR, 500 bp, partial coding sequence) sequences, and then detected their tissue distribution patterns, which showed that Ghrelin is mainly distribution in peripheral tissues, while GSHR is mainly in different brain divisions. Besides, the qPCR before and after feeding showed that the mRNA expressions of Ghrelin and GHSR were inhibited after feeding in telencephalon, diencephalon and mesencephalon. Subsequently, the food intake and appetite factor expressions were measured by i.c.v. co-injection of Ghrelin and GSHR antagonist. The results showed that Ghrelin promoted the food intake of Siberian sturgeon, which was reversed by its receptor antagonist. Besides, i.c.v. injection of Ghrelin decreased telencephalon CART expression while increased NPY expression in the three brain regions. In addition, to further explore the relationship of Ghrelin and CB1 signal regulating feeding, the co-injection of Ghrelin and CB1 antagonists was performed. The results showed that AM6545 (CB1 peripheral restricted antagonist) failed to affect the orexigenic effect of Ghrelin and the expression pattern of NPY mRNA in the telencephalon. While in the diencephalon, the increase of food intake and NPY mRNA expression induced by Ghrelin was completely reversed by Rimonabant (CB1 global antagonist). These results indicate Ghrelin-GSHR pathway promotes the food intake of Siberian sturgeon by inducing the expression of NPY in the diencephalon, and the stimulating effect will be reversed by cannabinoid receptor antagonism. This study provides a foundation for understanding the pathways Ghrelin and CB1 signals in appetite regulation of the teleost.
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Ghrelina , Receptores de Ghrelina , Animales , Ingestión de Alimentos , Endocannabinoides/metabolismo , Endocannabinoides/farmacología , Peces/fisiología , Ghrelina/metabolismo , Ghrelina/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Ghrelina/metabolismoRESUMEN
PURPOSE: This study was aiming to explore the risk factors contributing to enterostomy in neonates with Hirschsprung disease (HD) to provide a reference for clinicians to make treatment decisions. METHODS: Medical records of 284 patients diagnosed with HD during the neonatal period were retrospectively analyzed. The patients were divided into 2 groups based on operative intervention (one stage transanal pull-through, versus enterotomy and staged transanal pull-through). Univariate and multivariable logistic regression analysis was performed to identify risk factors contributing to enterostomy. RESULTS: The incidence of enterostomy was 12.0% (34/284) in neonates with HD. Univariate and multivariate logistic regression analysis showed that serum albumin < 25.4 g/L, radiographic results as subphrenic free air, and level of aganglionosis with long-segment or total colonic aganglionosis (TCA) were independent risk factors of enterostomy in neonates, with OR of 42.045 (6.131, 288.319), 285.558 (26.651, 3059.694) and 15.573 (4.319, 56.157), respectively. CONCLUSIONS: The low serum albumin level, bowel perforation, and level of aganglionosis with long-segment or TCA could influence the occurrence of enterostomy in neonates with HD.
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Enterostomía , Enfermedad de Hirschsprung , Enterostomía/efectos adversos , Enfermedad de Hirschsprung/cirugía , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Factores de Riesgo , Albúmina SéricaRESUMEN
Phthalates are a class of environmental endocrine disruptors. Previous studies have demonstrated that phthalate exposure can affect thyroid function; however, limited studies have assessed the associations between phthalate exposure and thyroid function, especially thyroid autoimmunity in pregnant women during the first trimester. We recruited participants from a cohort of pregnant women in Beijing, China, and collected urine samples to measure ten phthalate metabolites, serum samples to measure free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) during the first trimester. We included 325 pregnant women without thyroid diseases or dysfunction in this study. Associations between phthalate metabolites and thyroid function parameters were assessed with the Bayesian kernel machine regression (BKMR) model, multiple linear regression model, and restricted cubic spline. In the BKMR model analysis, compared to the 50th percentile, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels when phthalate metabolites were at or below the 40th percentile. Stratifying by body mass index, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels in normal weight women when phthalate metabolites were at or below the 45th percentile. However, total urinary phthalate metabolites levels were positively associated with serum TPOAb levels in underweight women when phthalate metabolites were at or below the 30th percentile. In restricted cubic spline analysis, L-shaped nonlinear associations of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), di-(2-ethylhexyl) phthalate (ΣDEHP), and inverted S-shaped nonlinear association of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with TPOAb were observed. In conclusion, our findings suggest that phthalate exposure may affect thyroid autoimmunity in underweight pregnant women during early pregnancy, and the potential effects of phthalate exposure on thyroid autoimmunity may be nonlinear.
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Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Teorema de Bayes , Exposición a Riesgos Ambientales , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/orina , Femenino , Humanos , Ácidos Ftálicos/orina , Embarazo , Primer Trimestre del Embarazo , Mujeres Embarazadas , Delgadez , Glándula Tiroides/metabolismoRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of transanal endorectal pull-through (TEPT) and the long-term outcomes in newborns with Hirschsprung disease (HD). METHODS: A total of 229 newborns with HD underwent one-stage TEPT between 2007 and 2020, and the diagnoses were confirmed by rectal biopsy. The perioperative clinical course for all patients was reviewed, and the postoperative short- and long-term outcomes were assessed. RESULTS: A total of 229 neonates (187 male and 42 female) had a median age at TEPT of 17 days (range 6-28 days). Sixty-eight patients (29.7%) underwent TEPT combined with an abdominal approach or laparoscopy. Early postoperative complications (using the Clavien-Dindo grading system) were documented in 36 patients (15.7%), and late postoperative complications were noted in 9 patients (3.9%). The follow-up period in the remaining 165 children ranged from 1.2 to 14.0 years (median 5.0 years). A total of 106 of the patients older than four years old took part in an interview about bowel function, and 85 patients (80.2%) had bowel function scores (BFS) ≥ 18. CONCLUSION: TEPT is effective and safe for HD in the neonatal period and presents with a low rate of complications and an acceptable outcome.
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Procedimientos Quirúrgicos del Sistema Digestivo , Enfermedad de Hirschsprung , Laparoscopía , Canal Anal/cirugía , Niño , Preescolar , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Femenino , Enfermedad de Hirschsprung/complicaciones , Humanos , Lactante , Recién Nacido , Laparoscopía/efectos adversos , Masculino , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
Intermolecular C-H silylation for the synthesis of acyclic silanes bearing a silicon-stereogenic center in one enantiomeric form remains unknown to date. Herein, we report the first enantioselective intermolecular C-H silylation of heteroarenes for the synthesis of acyclic silicon-stereogenic heteroarylsilanes. This process undergoes a rhodium-catalyzed direct intermolecular dehydrogenative Si-H/C-H cross-coupling, giving access to a variety of acyclic heteroarylated silicon-stereogenic monohydrosilanes, including bis-Si-stereogenic silanes, in decent yields with excellent chemo-, regio-, and stereo-control, which significantly enlarge the chemical space of the optically active silicon-stereogenic monohydrosilanes.
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N-N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of N-N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of N-N bisindole atropisomers via the palladium-catalyzed de novo construction of one indole skeleton is presented. A wide variety of N-N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indole-carbazole, and non-biaryl-indole atropisomers possessing a chiral N-N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol.
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Productos Biológicos , Paladio , Estereoisomerismo , Estructura Molecular , Indoles/química , Pirroles , Carbazoles , Preparaciones FarmacéuticasRESUMEN
Nonphotochemical quenching (NPQ), an intricate photoprotective process, plays fundamental roles in maintaining plant fitness. The PsbS protein is essential for the rapid induction of NPQ, and acts in a dose-dependent manner in leaves. However, little information is known on the transcriptional control of PsbS in land plants. Here we demonstrated that the expression of OsPsbS1 is directly upregulated by OsbZIP72 while repressed by OsMYBS2 in rice. We identified a new cis-element GACAGGTG in japonica OsPsbS1 promoter, to which OsbZIP72 could strongly bind and activate the expression of OsPsbS1. The new cis-element CTAATC confers specific binding for OsMYBS2 in japonica OsPsbS1 promoter. OsbZIP72 can be activated by SAPK1, and acts depending on the abscisic acid (ABA) signalling pathway. GF14A protein affects the repression activity of OsMYBS2 by regulating its nucleocytoplasmic shuttling, and Ser53 is necessary for OsMYBS2 to be retained in the cytoplasm. The inducibility of OsPsbS1 transcription under high light conditions in OsbZIP72 knockout lines was greatly impaired, while the repression of OsPsbS1 transcription under a low light environment in OsMYBS2 knockout lines was significantly alleviated. These results reveal cross-talk among NPQ processes, the ABA signalling pathway and abiotic stress signalling. The elaborate mechanisms may help enhance photoprotection and improve photosynthesis in rice.
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Oryza , Ácido Abscísico , Regulación de la Expresión Génica de las Plantas , Oryza/genética , Oryza/metabolismo , Fotosíntesis , Complejo de Proteína del Fotosistema II/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Estrés Fisiológico/genéticaRESUMEN
The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.