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Purpose: Acute ischemic stroke (AIS) has seriously threatened people's health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS. Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4. Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients. Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.
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To investigate the effects of Luhong Yixin Granules on myocardial fibrosis in rats with heart failure and its possible mechanism, a total of 60 male Wistar rats were randomly divided into the control group, model group, and low-, medium-and high-dose Luhong Yixin Granules groups, with 12 rats in each group. Except for those in the control group, rats in the other groups were induced by intraperitoneal injection of doxorubicin(DOX) into a rat model. After the Luhong Yixin Granules were dissolved in the same amount of normal saline, they were given by gavage at low, medium and high doses(2.8, 5.6, 11.2 g·kg~(-1)·d~(-1)), and the control group and the model group were given the same amount of normal saline by gavage for 40 days. After the end of dosing, echocardiography was used to measure left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS). Rat body weight(BW) and heart weight(HW) were calculated as HW/BW. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin-6(IL-6), interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), transforming growth factor-ß1(TGF-ß1), growth stimulation expressed gene 2 protein(ST2), N-terminal pro-B-type natriuretic peptide(NT-proBNP), galectin-3(Gal-3) and creatine kinase isoenzyme(CK-MB) in serum. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of myocardial tissue. Western blot and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, Smad7, α-smooth muscle actin(α-SMA), and collagen â (COL-â ), respectively. RESULTS:: showed that compared with those in the control group, LVEF, LVFS, and HW/BW in the model group were decreased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3, and CK-MB were increased(P<0.05). HE staining showed inflammatory changes in myocardial tissue; Masson staining showed decreases in the cross-sectional area and ventricular cavity area of the heart, and myocardial fibrosis of varying degrees(P<0.05). The protein and mRNA expression of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-â were increased(P<0.05), and the protein and mRNA expression of Smad7 protein was decreased(P<0.01). Compared with those in the model group, LVEF, LVFS and HW/BW of the low-, medium-and high-dose Luhong Yixin Granules groups were increased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3 and CK-MB were decreased(P<0.05). HE staining showed gradually reduced inflammatory changes of myocardial tissue, and Masson staining showed increased cross-sectional area and ventricular cavity area of the heart and decreased area of myocardial fibrosis(P<0.05). The protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-â were decreased(P<0.05), while the protein and mRNA expression levels of Smad7 were increased(P<0.05). Luhong Yixin Granules may be of great value in the treatment of heart failure by regulating the TGF-ß1/Smads signaling pathway, inhibiting the expression of inflammation-related proteins, reducing the deposition of extracellular matrix, and alleviating myocardial fibrosis.
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Medicamentos Herbarios Chinos , Fibrosis , Insuficiencia Cardíaca , Miocardio , Ratas Wistar , Transducción de Señal , Proteínas Smad , Factor de Crecimiento Transformador beta1 , Animales , Masculino , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Ratas , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Transducción de Señal/efectos de los fármacos , Miocardio/patología , Miocardio/metabolismo , Proteínas Smad/metabolismo , Proteínas Smad/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , HumanosRESUMEN
The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.
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Células Productoras de Anticuerpos , Camelus , Inmunoglobulina A , Inmunoglobulina G , Animales , Camelus/inmunología , Inmunoglobulina A/análisis , Células Productoras de Anticuerpos/inmunología , Envejecimiento , Factores de Edad , Masculino , Inmunidad Mucosa , Tonsila Faríngea/inmunología , Femenino , Tonsila Palatina/inmunología , Tonsila Palatina/citologíaRESUMEN
Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.
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Esclerosis Amiotrófica Lateral , Autoanticuerpos , Esclerosis Amiotrófica Lateral/inmunología , Esclerosis Amiotrófica Lateral/sangre , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Relevancia ClínicaRESUMEN
Cadmium (Cd) pollution severely affects plant growth and development, posing risks to human health throughout the food chain. Improved iron (Fe) nutrients could mitigate Cd toxicity in plants, but the regulatory network involving Cd and Fe interplay remains unresolved. Here, a transcription factor gene of alfalfa, MsbHLH115 was verified to respond to iron deficiency and Cd stress. Overexpression of MsbHLH115 enhanced tolerance to Cd stress, showing better growth and less ROS accumulation in Arabidopsis thaliana. Overexpression of MsbHLH115 significantly enhanced Fe and Zn accumulation and did not affect Cd, Mn, and Cu concentration in Arabidopsis. Further investigations revealed that MsbHLH115 up-regulated iron homeostasis regulation genes, ROS-related genes, and metal chelation and detoxification genes, contributing to attenuating Cd toxicity. Y1H, EMSA, and LUC assays confirmed the physical interaction between MsbHLH115 and E-box, which is present in the promoter regions of most of the above-mentioned iron homeostasis regulatory genes. The transient expression experiment showed that MsbHLH115 interacted with MsbHLH121pro. The results suggest that MsbHLH115 may directly regulate the iron-deficiency response system and indirectly regulate the metal detoxification response mechanism, thereby enhancing plant Cd tolerance. In summary, enhancing iron accumulation through transcription factor regulation holds promise for improving plant tolerance to Cd toxicity, and MsbHLH115 is a potential candidate for addressing Cd toxicity issues.
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BACKGROUND: Respiratory muscle training is a continuous and standardized training of respiratory muscles, but the evidence of the effects on early stroke patients is not clear. This meta-analysis aimed to investigate the effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke. METHODS: PubMed, Embase, PEDro, ScienceDirect, AMED, CINAHL, and China National Knowledge Infrastructure databases were searched from inception to December 8, 2023 for articles about studies that 1) stroke patients with age ≥ 18 years old. Early stroke < 3 months at the time of diagnosis, 2) respiratory muscle training, including inspiratory and expiratory muscle training, 3) the following measurements are the outcomes: respiratory muscle strength, respiratory muscle endurance, pulmonary function testing, dyspnea fatigue score, and functional capacity, 4) randomized controlled trials. Studies that met the inclusion criteria were extracted data and appraised the methodological quality and risk of bias using the Physiotherapy Evidence Database scale and the Cochrane Risk of Bias tool by two independent reviewers. RevMan 5.4 with a random effect model was used for data synthesis and analysis. Mean differences (MD) or standard mean differences (SMD), and 95% confidence interval were calculated (95%CI). RESULTS: Nine studies met inclusion criteria, recruiting 526 participants (mean age 61.6 years). Respiratory muscle training produced a statistically significant effect on improving maximal inspiratory pressure (MD = 10.93, 95%CI: 8.51-13.36), maximal expiratory pressure (MD = 9.01, 95%CI: 5.34-12.69), forced vital capacity (MD = 0.82, 95%CI: 0.54-1.10), peak expiratory flow (MD = 1.28, 95%CI: 0.94-1.63), forced expiratory volume in 1 s (MD = 1.36, 95%CI: 1.13-1.59), functional capacity (SMD = 0.51, 95%CI: 0.05-0.98) in patients with early stroke. Subgroup analysis showed that inspiratory muscle training combined with expiratory muscle training was beneficial to the recovery of maximal inspiratory pressure (MD = 9.78, 95%CI: 5.96-13.60), maximal expiratory pressure (MD = 11.62, 95%CI: 3.80-19.43), forced vital capacity (MD = 0.87, 95%CI: 0.47-1.27), peak expiratory flow (MD = 1.51, 95%CI: 1.22-1.80), forced expiratory volume in 1 s (MD = 0.76, 95%CI: 0.41-1.11), functional capacity (SMD = 0.61, 95%CI: 0.08-1.13), while inspiratory muscle training could improve maximal inspiratory pressure (MD = 11.60, 95%CI: 8.15-15.05), maximal expiratory pressure (MD = 7.06, 95%CI: 3.50-10.62), forced vital capacity (MD = 0.71, 95%CI: 0.21-1.21), peak expiratory flow (MD = 0.84, 95%CI: 0.37-1.31), forced expiratory volume in 1 s (MD = 0.40, 95%CI: 0.08-0.72). CONCLUSIONS: This study provides good-quality evidence that respiratory muscle training is effective in improving respiratory muscle strength, pulmonary function, and functional capacity for patients with early stroke. Inspiratory muscle training combined with expiratory muscle training seems to promote functional recovery in patients with early stroke more than inspiratory muscle training alone. TRIAL REGISTRATION: Prospero registration number: CRD42021291918.
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PURPOSE: The motor symptoms (MS) of Parkinson's disease (PD) have been affecting the quality of life in patients. In clinical practice, most patients with PD report that MS are more severe in winter than in summer, and hyperthermic baths (HTB) could temporarily improve MS. The study aimed to evaluate the effects of seasonal variation and aquatic thermal environment of HTB on the MS of PD. PATIENTS AND METHODS: A cross-sectional study of 203 Chinese Han patients was performed. Univariate and multivariate analyses were performed to analyze seasonal variation in MS relative to baseline data (sex, age at onset, duration, season of birth, Hoehn and Yahr stage, family history, levodopa equivalent dose, and the effect of HTB on MS). Ten subjects participated in the HTB study, and one patient dropped out. The paired Wilcoxon rank test was used to assess the differences in the Movement Disorder Society-United Parkinson's disease Rating Scale (MDS-UPDRS) part III motor examination total scores and the modified Webster Symptoms Score between non-HTB and before HTB and between non-HTB and after HTB. RESULTS: The improvement of MS after HTB was an independent risk factor for seasonal variation in MS (OR, 25.203; 95% CI, 10.951-58.006; p = .000). Patients with PD had significant improvements in the MDS-UPDRS part III motor examination total scores, especially in bradykinesia (p = .043), rigidity (p = .008), posture (p = .038), and rest tremor amplitude (p = .047). CONCLUSION: Seasonal variation in temperature and water temperature of HTB may affect MS in some patients with PD. Simple HTB could be recommended as physiotherapy for patients with PD who report temperature-sensitive MS.
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Enfermedad de Parkinson , Salicilatos , Humanos , Estudios Transversales , Enfermedad de Parkinson/tratamiento farmacológico , Proyectos Piloto , Calidad de Vida , TemperaturaRESUMEN
This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shenmai Injection + conventio-nal western medicine > Shenfu Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Puerarin Injection + conventional wes-tern medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine > Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
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Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Medicina Tradicional China , Péptido Natriurético Encefálico , Metaanálisis en Red , Calidad de Vida , Volumen Sistólico , Función Ventricular Izquierda , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Hepatitis E virus (HEV) is a frequently overlooked causative agent of acute hepatitis. Evaluating the long-term durability of hepatitis E vaccine efficacy holds crucial importance. METHODS: This study was an extension to a randomised, double-blind, placebo-controlled, phase-3 clinical trial of the hepatitis E vaccine conducted in Dontai County, Jiangsu, China. Participants were recruited from 11 townships in Dongtai County. In the initial trial, a total of 112 604 healthy adults aged 16-65 years were enrolled, stratified according to age and sex, and randomly assigned in a 1:1 ratio to receive three doses of hepatitis E vaccine or placebo intramuscularly at month 0, month 1, and month 6. A sensitive hepatitis E surveillance system including 205 clinical sentinels, covering the entire study region, was established and maintained for 10 years after vaccination. The primary outcome was the per-protocol efficacy of hepatitis E virus vaccine to prevent confirmed hepatitis E occurring at least 30 days after administration of the third dose. Throughout the study, the participants, site investigators, and laboratory staff remained blinded to the treatment assignments. This study is registered with ClinicalTrials.gov (NCT01014845). FINDINGS: During the 10-year study period from Aug 22, 2007, to Oct 31, 2017, 90 people with hepatitis E were identified; 13 in the vaccine group (0·2 per 10 000 person-years) and 77 in the placebo group (1·4 per 10 000 person-years), corresponding to a vaccine efficacy of 83·1% (95% CI 69·4-91·4) in the modified intention-to-treat analysis and 86·6% (73·0 to 94·1) in the per-protocol analysis. In the subsets of participants assessed for immunogenicity persistence, of those who were seronegative at baseline and received three doses of hepatitis E vaccine, 254 (87·3%) of 291 vaccinees in Qindong at the 8·5-year mark and 1270 (73·0%) of 1740 vaccinees in Anfeng at the 7·5-year mark maintained detectable concentrations of antibodies. INTERPRETATION: Immunisation with this hepatitis E vaccine offers durable protection against hepatitis E for up to 10 years, with vaccine-induced antibodies against HEV persisting for at least 8·5 years. FUNDING: National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and the Fundamental Research Funds for the Central Universities.
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Hepatitis E , Vacunas contra Hepatitis Viral , Adulto , Humanos , Anticuerpos Antivirales , Hepatitis E/prevención & control , VacunaciónRESUMEN
Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E-driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E-driven PTCs and that loss of cilia may be associated with lymph node metastasis. In PTC cells, the BRAFV600E mutation maintained the aggressiveness of PTC, which was partially related to loss of PCs. Our work confirms that BRAFV600E mutation-driven PC downregulation contributes to maintaining the aggressiveness of PTCs and that manipulating PC can potentially reduce the adverse incidence of PTC in a range of conditions.
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Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/patología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Cilios/metabolismo , Regulación hacia Abajo/genética , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Mutación/genéticaRESUMEN
Background: Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision-making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods: A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5- and 10-year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C-index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan-Meier (K-M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five- and ten-year survival rates for the two groups were shown using K-M curves. Results: The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C-indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5- and 10-year risk of cardiac death. The model exhibited moderate predictive power for 5- and 10-year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions: Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.
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BACKGROUND: Toll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling cascades. However, the precise distribution and age-related alterations of TLR8 in the spleens of Bactrian camels have not yet been investigated. This study aimed to prepare a rabbit anti-Bactrian camel TLR8 polyclonal antibody and elucidate the distribution of TLR8 in the spleens of Bactrian camels at different age groups. The methodology involved the construction of the pET-28a-TLR8 recombinant plasmid, followed by the expression of TLR8 recombinant protein via prokaryotic expression. Subsequently, rabbits were immunized with the purified protein to prepare the TLR8 polyclonal antibody. Finally, twelve Alashan Bactrian camels were categorized into four groups: young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). These camels received intravenous sodium pentobarbital (20 mg/kg) anesthesia and were exsanguinated to collect spleen samples. Immunohistochemical techniques were employed to observe and analyze the distribution patterns and age-related changes of TLR8 in the spleen. RESULTS: The results showed that the TLR8 recombinant protein was expressed in the form of inclusion body with a molecular weight of 52 kDa, and the optimal induction condition involved 0.3 mmol/L IPTG induction for 8 h. The prepared antibody yielded a titer of 1:32 000, and the antibody demonstrated specific binding to TLR8 recombinant protein. TLR8 positive cells exhibited a consistent distribution pattern in the spleen across different age groups of Bactrian camels, primarily scattered within the periarterial lymphatic sheath of the white pulp, marginal zone, and red pulp. The predominant cell type expressing TLR8 was macrophages, with expression also observed in neutrophils and dendritic cells. Statistical analysis revealed that there were significant differences in the distribution density of TLR8 positive cells among different spleen regions at the same age, with the red pulp, marginal zone, and white pulp showing a descending order (P<0.05). Age-related changes indicated that the distribution density in the marginal zone and red pulp exhibited a similar trend of initially increasing and subsequently decreasing from young to old camels. As camels age, there was a significant decrease in the distribution density across all spleen regions (P<0.05). CONCLUSIONS: The results confirmed that this study successfully prepared a rabbit anti-Bactrian camel TLR8 polyclonal antibody with good specificity. TLR8 positive cells were predominantly located in the red pulp and marginal zone of the spleen, signifying their pivotal role in the innate immune response of the spleen. Aging was found to significantly reduce the density of TLR8 positive cells, while leaving their scattered distribution characteristics unaffected. These findings provide valuable support for further investigations into the immunomorphology and immunosenescence of the spleen in Bactrian camels.
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Camelus , Bazo , Animales , Conejos , Bazo/metabolismo , Camelus/anatomía & histología , Receptor Toll-Like 8 , Inmunoglobulina G , Proteínas RecombinantesRESUMEN
BACKGROUND: Currently, a variety of new nursing methods and routine nursing have been widely used in the nursing of gastrointestinal surgery patients. AIM: To investigate the effect of follow-up protocol based on the Omaha System on self-care ability and quality of life of gastrointestinal surgery patients. METHODS: A total of 128 patients with inflammatory bowel disease in gastrointestinal surgery in gastrointestinal surgery from March 2019 to August 2021 were divided into A (n = 64) and B (n = 64) groups according to different nursing methods. The group A received a follow-up program Omaha System-based intervention of the group B, whereas the group B received the routine nursing intervention. Medical Coping Modes Questionnaire, Crohn's and Colitis Knowledge Score (CCKNOW), inflammatory bowel disease questionnaire (IBDQ), Exercise of Self-nursing Agency Scale (ESCA), The Modified Mayo Endoscopic Score, and Beliefs about Medicine Questionnaire (BMQ) were compared between the two groups. RESULTS: Following the intervention, the group A were facing score significantly increased than group B, while the avoidance and yield scores dropped below of group B (all P < 0.05); in group A, the level of health knowledge, personal care abilities, self-perception, self-awareness score and ESCA total score were more outstanding than group B (all P < 0.05); in group A the frequency of defecation, hematochezia, endoscopic performance, the total evaluation score by physicians and the disease activity were lower than group B (all P < 0.05); in the group A, the total scores of knowledge in general, diet, drug, and complication and CCKNOW were higher than group B (all P < 0.05); in group A, the necessity of taking medicine, score of medicine concern and over-all score of BMQ were more significant than group B (all P < 0.05); at last in the group A, the scores of systemic and intestinal symptoms, social and emotional function, and IBDQ in the group A were higher than group B (all P < 0.05). CONCLUSION: For gastrointestinal surgery patients, the Omaha System-based sequel protocol can improve disease awareness and intervention compliance, help them to face the disease positively, reduce disease activity, and improve patients' self-nursing ability and quality of life.
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Background: The pathogen of angiostrongyliasis is the parasite Angiostrongylus cantonensis, and the transcriptome profiling of the male adult was unclear. We aimed to understand how the male adults adapt, so the expression profile of A. cantonensis adult males was analyzed. Methods: In order to improve the understanding of the transcriptome of adult males, RNA from three groups of male adult A. cantonensis was extracted and reverse transcribed to construct cDNA libraries. After sequencing, annotation of unigenes and transcripts was performed by querying the NR (Non-Redundant Protein Sequence Database), GO (Gene Ontology) and COG/KOG (Clusters of Orthologous Groups of proteins/euKaryotic Ortholog Groups) databases. Results: For each group of adults, 43,260,894 raw reads and 43,200,341 clean reads were obtained. After successful assembly, 87,649 unigenes and 146,895 transcripts were obtained. Annotation of the unigenes and transcripts was identical and male adults expressed a series of genes encoding proteins specific to the male gender at the adult stage, such as proteins involved in energy metabolism, energy synthesis and transport. Expression of the ribosome pathway suggests a relationship with the physical activities during the adult male stage. Conclusion: The transcriptome analysis is a good reference to understand further the expression profile of male adult A. cantonensis.
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Seed size and weight are important factors that influence soybean yield. Combining the weighted gene co-expression network analysis (WGCNA) of 45 soybean accessions and gene dynamic changes in seeds at seven developmental stages, we identified candidate genes that may control the seed size/weight. Among these, a PLATZ-type regulator overlapping with 10 seed weight QTLs was further investigated. This zinc-finger transcriptional regulator, named as GmPLATZ, is required for the promotion of seed size and weight in soybean. The GmPLATZ may exert its functions through direct binding to the promoters and activation of the expression of cyclin genes and GmGA20OX for cell proliferation. Overexpression of the GmGA20OX enhanced seed size/weight in soybean. We further found that the GmPLATZ binds to a 32-bp sequence containing a core palindromic element AATGCGCATT. Spacing of the flanking sequences beyond the core element facilitated GmPLATZ binding. An elite haplotype Hap3 was also identified to have higher promoter activity and correlated with higher gene expression and higher seed weight. Orthologues of the GmPLATZ from rice and Arabidopsis play similar roles in seeds. Our study reveals a novel module of GmPLATZ-GmGA20OX/cyclins in regulating seed size and weight and provides valuable targets for breeding of crops with desirable agronomic traits.
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Glycine max , Transcriptoma , Glycine max/genética , Transcriptoma/genética , Fitomejoramiento , Sitios de Carácter Cuantitativo , Semillas/genéticaRESUMEN
HLA-B*15:270 differs from HLA-B*15:12:01 by one nucleotide substitution at position 679 in exon 4.
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Antígenos HLA-B , Nucleótidos , Humanos , Alelos , Secuencia de Bases , Antígenos HLA-B/genética , Exones/genética , Análisis de Secuencia de ADNRESUMEN
Background: Chronic urticaria (CU) is a commonly seen skin disorder featured by recurring wheals, with or without angioedema, lasting for at least 6 weeks. Runzao Zhiyang capsule (RZC) has been widely applied to treat patients with CU. This study is aimed at systematically evaluating the efficacy and safety of RZC in treating CU. Materials and Methods: Randomized controlled trials (RCTs) of RZC on treating CU from Chinese and English databases were searched. Data were collected by two independent researchers. The Cochrane Collaboration tool was adopted for evaluating the risk of bias. The meta-analysis was performed with Review Manager 5.3 software. Sensitivity analysis and publication bias assessment were conducted by Stata 14.0 software. Results: Totally 27 studies were included in the analysis, involving 2,703 patients. The pooled results showed that compared with second-generation H1-antihistamines (sgAHs) therapy alone, RZC combined with sgAHs is more effective in improving the total effective rate (RR = 1.32, 95% CI: 1.25 to 1.39, p < 0.00001), the quality of life measured by Dermatology Life Quality Index (DLQI) (MD = -2.63, 95% CI: -3.68 to -1.58, p < 0.00001) and the serum IFN-γ level (SMD = 3.10, 95% CI: 1.58 to 4.62, p < 0.0001), and reducing the recurrence rate (RR = 0.39, 95% CI: 0.27 to 0.55, p < 0.00001), the serum total IgE level (SMD = -2.44, 95% CI: -3.51 to -1.38, p < 0.00001), the serum IL-4 level (SMD = -2.96, 95% CI: -4.10 to -1.83, p < 0.00001), and the incidence of adverse events including dizziness, fatigue, dry mouth, and constipation (RR = 0.53, 95% CI: 0.33 to 0.85, p = 0.009; RR = 0.46, 95% CI: 0.26 to 0.84, p = 0.01; RR = 0.57, 95% CI: 0.34 to 0.95, p = 0.03; RR = 0.24, 95% CI: 0.07 to 0.85, p = 0.03). Conclusion: The current evidence indicates that RZC may be an efficient therapeutic regimen in patients with CU. Nevertheless, owing to the suboptimal quality of the included studies, more large-scale, well-designed RCTs are required to verify the obtained findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier: CRD42022313177.
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BACKGROUND: Hepatocellular carcinoma (HCC) is an exceedingly prevalent malignancy with an exceptionally poor prognosis. Targeted therapy is an effective treatment option for patients with advanced HCC. However, there have been no bibliometric analyses of targeted therapies for HCC. METHODS: This study aimed to assess the current status and future directions of targeted therapy for HCC to provide future scholars with clearer research contents and popular themes. Methods: Literature on targeted therapy for HCC from 2008 to 2022 was obtained from the Web of Science (WoS) and assessed using bibliometric methodology. Additionally, the VOS viewer was applied in the visualization study to conduct bibliographic coupling, co-authorship, co-citation, and co-occurrence analyses of publications. RESULTS: A total of 10,779 papers were subsequently selected. Over the past 15 years, there has been a progressive increase in the number of publications on an annualized basis. China released the most publications in the field, whereas the United States had the highest H-index. Cancers published the most papers. Fudan University had the greatest sway in this area. Studies could be divided into 5 clusters: "Gene and expression research," "Mechanism study," "Nanoparticle study," "Targeted drug research," and "Clinical study." CONCLUSIONS: In the upcoming years, more papers on targeted therapy for HCC are expected to be released, demonstrating the potential for this topic to flourish. Particularly, "Clinical study" is the following trendy topic in this field. Other research subfields may likewise exhibit a continuous tendency towards balanced development.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Autoria , Bibliometría , ChinaRESUMEN
Bisabosqual-type meroterpenoids are fungi-derived polyketide-terpenoid hybrids bearing a 2,3,3a,3a1,9,9a-hexahydro-1H-benzofuro[4,3,2-cde]chromene skeleton (6/6/6/5 ring system) or its seco-C-ring structure, and exhibit diverse bioactivities. Their unique structural architecture and impressive biological activities have led to considerable interest in discovering new analogues. However, to date, only nine analogues have been identified. Herein, we reported the isolation and identification of six new bisabosqual-type meroterpenoids stachybisbins C-H (1-6), together with one known compound bisabosqual C (7), from Stachybotrys bisbyi PYH05-7. Intriguingly, we found that 7, which contains the intact tetracyclic skeleton, can be non-enzymatically converted into its seco derivative stachybisbin I (8), unveiling the biosynthetic relationship between bisabosquals and seco-bisabosquals. Moreover, based on CRISPR/Cas9-mediated gene disruption, we revealed that the three-gene cluster responsible for the formation of LL-Z1272ß is associated with the biosynthesis of bisabosqual-type meroterpenoids, and then proposed a plausible route to 1-8.
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Benzopiranos , Policétidos , Radiofármacos , TerpenosRESUMEN
Exploring the expression characteristics of FcµR in small intestinal lymph nodes of bactrian camels can lay the foundation for further revealing the function of FcµR. The FcµR expression characteristics were systematically analysed by using prokaryotic expression, antibody preparation, immunohistochemical staining and statistical analysis. FcµR positive cells were mainly located in the lymphoid follicles and their numbers decreased in the order of duodenal lymph nodes, jejunal lymph nodes and ileal lymph nodes, and the number of positive cells was statistically significant between different intestinal segments (P<0.05). The FcµR is expressed in lymphoid follicular B cells, which not only facilitates the body's ability to regulate secretory IgM levels, but also acts as a local immune defence barrier. The small intestine has dual functions of immune tolerance and immune response, the proximal part mainly focuses on immune tolerance, and the distal part mainly focuses on immune response. This distribution ensures the unity of the duodenal absorption and immune defence, and also significantly increases the efficiency of the entire small intestine, which is why the number of FcµR positive cells decreases in the order of duodenal lymph nodes, jejunal lymph nodes and ileal lymph nodes.