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Protein scaffolds play a vital role in drug delivery systems. However, few research studies have been focused on loading hydrophobic drugs on protein scaffolds in biomedical fields. Here, we report on the development of protein microspheres and nanofibers by a simple ice-templating approach and their use as scaffolds for the controlled release of hydrophobic drugs, with bovine serum albumin (BSA) as the model protein and curcumin as the model hydrophobic drug. The BSA scaffolds display the unique nanofibrous and microspherical structures. This is a surprising discovery because there has been no report on the formation of microspheres via simple ice-templating of solutions or suspensions. To further understand the formation of microspheres by this approach, lysozyme, papain, and their composites with BSA are also studied. It is speculated that nanoparticles are first formed in aqueous BSA solution, attributed to the overlapping of hydration layers and autoassembly of inner hydrophobic cores of BSA globular molecules. Nanoprecipitation and soaking evaporation approaches are then used to load curcumin into the BSA scaffolds, followed by cross-linking with glutaraldehyde vapor to improve stability in an aqueous medium. The controlled release of curcumin is demonstrated, paving the way for various hydrophobic drugs loaded into this biodegradable and nonimmunogenic protein scaffold for potential treatments of diverse diseases.
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BACKGROUND: Whether hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and acute esophagogastric variceal bleeding (EGVB) can improve the success rate of endoscopic hemostasis and overall survival (OS) from transjugular intrahepatic portosystemic shunt (TIPS) remains controversial. AIM: To compare the clinical outcomes between TIPS and standard treatment for such HCC patients. METHODS: This monocenter, retrospective cohort study included patients diagnosed as HCC with PVTT and upper gastrointestinal bleeding. Patients were grouped by the treatment (TIPS or standard conservative treatment). The success rate of endoscopic hemostasis, OS, rebleeding rates, and main causes of death were analyzed. RESULTS: Between July 2015 and September 2021, a total of 77 patients (29 with TIPS and 48 with standard treatment) were included. The success rate of endoscopic hemostasis was 96.6% in the TIPS group and 95.8% in the standard treatment group. All the 29 patients in TIPS group successful underwent TIPS procedure and had a better OS compared with standard treatment within the first 160 days after treatment (68 days vs 43 days, P = 0.022), but shorter OS after 160 days (298 days vs 472 days, P = 0.022). Cheng's Classification of PVTT, total bilirubin and Child-Pugh class were independently negative associated with OS (all P < 0.05). The main causes of death were liver failure or hepatic encephalopathy (75.9%) in the TIPS group and rebleeding (68.8%) in the standard treatment. CONCLUSION: TIPS could reduce the risk of early death due to rebleeding and prolong short-term survival in HCC patients with PVTT and acute EGVB, which deserves further investigation.
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BACKGROUND: Stellate ganglion block is a commonly used sympathetic nerve block technique that restores the balance of the sympathetic and vagal nervous systems of the body and inhibits sympathetic nerve activity. AIM: To analyze the effect of a stellate ganglion block combined with total diploma intravenous anesthesia on postoperative pain and immune function in patients undergoing laparoscopic radical gastric cancer (GC) surgery to provide a reference basis for the formulation of anesthesia protocols for radical GC surgery. METHODS: This study included 112 patients who underwent laparoscopic radical surgery for GC between January 2022 and March 2024. There was no restriction on sex. The patient grouping method used was a digital random table method, and the number of cases in each group was 56. The control group was administered total intravenous anesthesia, and the observation group compounded the stellate ganglion block according to the total intravenous anesthesia protocol. Postoperative hemodynamics, pain levels, and immune indices were compared between the groups. RESULTS: The heart rate and mean arterial pressure in the observation group after intubation were lower than those in the control group (P < 0.05). Pain levels were compared between the two groups at 2 hours, 12 hours, 24 hours, and 48 hours after surgery (P > 0.05). The number of CD3+, CD4+, and CD4+/CD8+ cells at the end of surgery was higher in the observation group than in the control group, and the number of CD8+ cells was lower in the observation group than in the control group (P < 0.05). There were no significant differences between the two groups in terms of propofol dosage, awakening time, extubation time, or postoperative adverse reactions (P > 0.05). CONCLUSION: The application of a stellate ganglion block combined with total intravenous anesthesia had no significant effect on postoperative pain levels in patients undergoing laparoscopic radical GC surgery. However, it can safely reduce the effect of surgery on the immune function of patients and is worth applying in clinical practice.
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BACKGROUND: Osteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes. METHODS: A proteome-wide association study (PWAS) was performed based on OA and its subtypes genome-wide association studies (GWAS) summary datasets and the protein quantitative trait loci (pQTL) data. Subsequently, Mendelian randomization (MR) and colocalization analysis was conducted to estimate the associations between protein and OA risk. The replication analysis was performed in an independent dataset of human plasma pQTL data. RESULTS: The abundance of seven proteins was causally related to OA, two proteins to knee OA and six proteins to hip OA, respectively. We replicated 2 of these proteins using an independent pQTL dataset. With the further support of colocalization, and higher ECM1 level was causally associated with a higher risk of OA and hip OA. Higher PCSK1 level was causally associated with a lower risk of OA. And higher levels of ITIH1, EFEMP1, and ERLEC1 were associated with decreased risk of hip OA. CONCLUSION: Our study provides new insights into the genetic component of protein abundance in OA and a promising therapeutic target for future drug development.
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Estudo de Associação Genômica Ampla , Proteoma , Locos de Características Quantitativas , Humanos , Osteoartrite/genética , Osteoartrite/sangue , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/sangue , Predisposição Genética para Doença/genética , Osteoartrite do Quadril/genética , Osteoartrite do Quadril/sangue , Análise da Randomização Mendeliana , Masculino , Feminino , Terapia de Alvo Molecular/métodosRESUMO
Simultaneous detection of the dynamic distribution of long-chain fatty acid ethyl esters (LCFAEEs) during Baijiu distillation is crucial for optimizing its flavor and health attributes. In this study, we synthesized a simple, cost-effective Fe3O4@NH2 adsorbent to simultaneously extract eight LCFAEEs from Baijiu. Through density functional theory and adsorption experiments, we elucidated 1,6-hexanediamine as a surface modifier, with the -NH2 groups providing adsorption sites for the LCFAEEs via hydrogen-bonding interactions and van der Waals forces. Additionally, we established the magnetic solid-phase extraction-GC-MS extraction technique combined with stable isotope dilution analysis to analyze LCFAEEs. This method revealed the dynamic distribution patterns of LCFAEEs during strong aroma-type Baijiu (SAB) distillation. We observed that the concentrations of the eight LCFAEEs gradually decreased with prolonged distillation and were significantly correlated with ethanol concentration. To ensure optimal flavor and clarity in SAB, it is recommended to select the heart-stage base Baijiu with an alcohol content of 58%-63%.
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Destilação , Ésteres , Ácidos Graxos , Aromatizantes , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Ésteres/química , Destilação/métodos , Adsorção , Ácidos Graxos/química , Odorantes/análise , Aromatizantes/química , Extração em Fase Sólida/métodos , Extração em Fase Sólida/instrumentação , Nanopartículas de Magnetita/química , Bebidas Alcoólicas/análiseRESUMO
This review summarizes the progress in the research on polyoxometalate (POM)-decorated gold (Au) and silver (Ag) core-shell structures (Au/Ag@POMs), emphasizing their substantial application potential in catalysis, medicine, and biology. It outlines the central strategies for fabricating Au/Ag@POMs with diverse morphologies and dimensions, leveraging POMs as protective ligands and reducing agents as well as for ligand exchange. Of particular note is the focus on the analysis of the nanoparticle size, shape, and intricate architecture of POM shells using cryo-electron microscopy techniques. By integrating recent findings on atomically precise POM-stabilized nanoclusters, this review delves deeper into understanding surface interface structures, intrinsic atomic architectures, and electronic interactions between POM shells and metallic cores. Collectively, advancements in this field underscore significant strides in the controllable synthesis and precise structural manipulation of Au/Ag@POM architectures, thus paving the way for engineering high-performance metal catalysts.
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BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory and highly pruritic skin condition characterized by the infiltration of immune cells, notably eosinophils and mast cells. Mast cells (MCs) critically participate in the complex pathogenesis of AD through multiple pathways and have recently garnered growing attention in research. Despite the abundance of related studies published over the years, a comprehensive bibliometric analysis on this topic remains lacking. OBJECTIVE: Our objective was to perform an up-to-date bibliometric analysis of the literature focusing on the relationship between MCs and AD. This analysis would provide valuable insights through a thorough bibliometric review, enabling a clearer understanding of the current research landscape, pinpointing key studies, and detecting emerging trends within this field. METHODS: We searched the Web of Science Core Collection (WoSCC) database on 15 July 2024. The data retrieval strategy was structured as follows: #1: TS = ("mast cells") OR TS = ("mast cell") OR TS = ("mastocyte"); #2: TS = ("atopic dermatitis") OR TS = ("atopic eczema") Final data: (#1 AND #2). A total of 2272 items published between 2001 and 2024 were included. Several scientometric visualization tools, including VOSviewer, R-bibliometrix, CiteSpace and an online analytical platform, were utilized to conduct text mining and to visualize the bibliometric data, facilitating a comprehensive analysis of research trends and patterns. RESULTS: Out of the initial 2272 articles retrieved, 2168 were selected for analysis after applying inclusion and exclusion criteria based on publication type. The findings indicate a steady and substantial exponential growth in the annual number of publications focused on the relationship between over the years. The South Korea (547/2168), USA (465/2168) and Japan (436/2168) were the major contributors within this field, collectively constituting more than half of the total publications. To clarify the underlying mechanisms and role of MCs in the pathogenesis of AD and to make MCs prime targets for therapeutic intervention have garnered the most attention in this field. According to references analysis, the research emphasis has shifted to developing MC-related therapeutics and intervention and regulating the immune system of AD patients through modulating the activity of various immune cells. On the basis of keywords analysis, we outlined the following research frontiers and hotpots in the future: the role of oxidative stress in the pathogenesis; imbalance in the different types of T helper (Th) cells during immune response; skin barrier and barrier dysfunction; improving quality of life; sensory neurons; biological agents and small-molecule drugs. Furthermore, IL-13, IL-4, NFKB1, BCGF-1 and CD4 ranked as the top five genes that have received the most investigative attention in the intersection of MCs and AD. CONCLUSION: In a word, this analysis would greatly benefit from a thorough bibliometric review to gain a deeper understanding of the current research landscape, identify pivotal studies and pinpoint emerging trends in the field of MCs and AD. Meanwhile, our findings offered researchers a holistic perspective of ongoing developments, serving as a valuable resource for guiding future research and informing decision-making for both researchers and policymakers in this area.
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Bibliometria , Dermatite Atópica , Mastócitos , Dermatite Atópica/imunologia , Humanos , Mastócitos/imunologia , AnimaisRESUMO
BACKGROUND: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. MATERIALS AND METHODS: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 µM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. RESULTS: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. CONCLUSION: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.
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AIM: To psychometrically validate the Chinese version of the dry eye-related quality-of-life score questionnaire (DEQS-CHN) among Chinese patients with dry eye. METHODS: This study involved 231 participants, including 191 with dry eye disease (DED) comprising the dry eye disease group, and 40 healthy participants forming the control group. Participants were required to complete the DEQS-CHN, and Chinese dry eye questionnaire and undergo clinical tests including the fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I test. To assess the internal consistency and retest reliability, Cronbach's α and the intraclass correlation coefficient (ICC) were employed. Content validity was assessed by item-level content validity index (ICV) and an average scale-level content validity index (S-CVI/Ave). Construct validity was assessed by confirmatory factor analysis. The concurrent validity was assessed by calculating correlations between DEQS-CHN and Chinese dry eye questionnaire. Discriminative validity was evaluated through non-parametric tests, with receiver operating characteristic (ROC) curve serving as conclusive indicators of the questionnaire's distinguishing capability. RESULTS: The Cronbach's α coefficients for frequency and degree of ocular symptoms, impact on daily life, and summary score were 0.736, 0.704, 0.811, 0.818, 0.861, and 0.860, respectively, and the ICC were 0.611, 0.677, 0.715, 0.769, 0.711, and 0.779, respectively. All I-CVI scores ranged from 0.833 to 1.000, with an S-CVI/Ave of 0.956. Confirmatory factor analysis results exhibited a well-fitting model consistent with the original questionnaire [χ 2/df=2.653, incremental fit index (IFI)=0.924, comparative fit index (CFI)=0.924, Tucker-Lewis index (TLI)=0.909, and root mean square error of approximation (RMSEA)=0.065]. There was a moderate positive correlation between the DEQS-CHN and the Chinese dry eye questionnaire (r 2=0.588). The dry eye group demonstrated significantly higher scores compared to the control group, and the area under the curve (AUC) value was 0.8092. CONCLUSION: The DEQS-CHN has been demonstrated as a valid and reliable instrument for assessing the impact of dry eye disease on the quality of life among Chinese individuals with DED.
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BACKGROUND: The incidence and mortality rates of primary hepatocellular carcinoma (HCC) are high, and the conventional treatment is radiofrequency ablation (RFA) with transcatheter arterial chemoembolization (TACE); however, the 3-year survival rate is still low. Further, there are no visual methods to effectively predict their prognosis. AIM: To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model. METHODS: Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded. We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software (version 4.1.2). Internal verification was performed using the bootstrapping technique. The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index (CI), calibration curve, and receiver operating characteristic curve. RESULTS: Of the 150 patients treated with RFA and TACE, 92 (61.33%) developed recurrence and metastasis. Logistic regression analysis identified six variables, and a predictive model was created. The internal validation results of the model showed a CI of 0.882. The correction curve trend of the prognosis prediction model was always near the diagonal, and the mean absolute error before and after internal validation was 0.021. The area under the curve of the prediction model after internal verification was 0.882 [95% confidence interval (95%CI): 0.820-0.945], with a specificity of 0.828 and sensitivity of 0.656. According to the Hosmer-Lemeshow test, χ 2 = 3.552 and P = 0.895. The predictive model demonstrated a satisfactory calibration, and the decision curve analysis demonstrated its clinical applicability. CONCLUSION: The prognosis of patients with HCC after RFA and TACE is affected by several factors. The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.
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Statins are well-tolerated and widely available lipid-lowering medications with neuroprotective effects against traumatic brain injury (TBI). However, whether delayed statin therapy starting in the subacute phase promotes recovery after TBI is unknown. Elongation of the very long-chain fatty acid protein 1 (ELOVL1) is involved in astrocyte-mediated neurotoxicity, but its role in TBI and the relationship between ELOVL1 and statins are unclear. We hypothesized that delayed simvastatin treatment promotes neurological functional recovery after TBI by regulating the ELOVL1-mediated production of very long-chain fatty acids (VLCFAs). ICR male mice received daily intragastric administration of 1, 2 or 5mg/kg simvastatin on Days 1-14, 3-14, 5-14, or 7-14 after cryogenic TBI (cTBI). The results showed that simvastatin promoted motor functional recovery in a dose-dependent manner, with a wide therapeutic window of at least 7 days postinjury. Meanwhile, simvastatin inhibited astrocyte and microglial overactivation and glial scar formation, and increased total dendritic length, neuronal complexity and spine density on day 14 after cTBI. The up-regulation of ELOVL1 expression and saturated VLCFAs concentrations in the cortex surrounding the lesion caused by cTBI was inhibited by simvastatin, which was related to the inhibition of the mTOR signaling. Overexpression of ELOVL1 in astrocytes surrounding the lesion using HBAAV2/9-GFAP-m-ELOVL1-3xFlag-EGFP partially attenuated the benefits of simvastatin. These results showed that delayed simvastatin treatment promoted functional recovery and brain tissue repair after TBI through the downregulation of ELOVL1 expression by inhibiting mTOR signaling. Astrocytic ELOVL1 may be a potential target for rehabilitation after TBI.
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Low temperature (LT) is an important environmental factor affecting the growth and yield of plants. Melatonin (MT) can effectively enhance the LT tolerance of cucumber. This study found that LT stress induced the expression of Comt1 (caffeic acid O-methyltransferase 1), with the highest expression being about 2-times that of the control. Meanwhile, the content of MT was found to be roughly 63.16% of that in the control samples. Compared with LT treatment alone, exogenous MT pretreatment upregulated the expression levels of TOR (Target of rapamycin), PIN1 (Pin-formed 1), and YUC4 (YUCCA 4), with maximum upregulations reaching approximately 66.67%, 79.32%, and 42.86%, respectively. These results suggest that MT may modulate the tolerance of cucumber seedlings to LT stress by regulating the expression of TOR, PIN1, and YUC4. In addition, co-treatment with AZD-8055 (a TOR inhibitor) or NPA (N-1-naphthylphthalamic acid, an auxin polar transport inhibitor) and MT attenuated MT-induced resistance to LT stress, leading to higher levels of reactive oxygen species (ROS), reduced antioxidant defense capacity, and increased damage to the membrane system in cucumber seedlings. Concurrently, the content of osmoregulatory substances and the photosynthesis decreased. These results demonstrate that both TOR and auxin were required for MT to alleviate LT-induced damage in cucumber. In summary, the present study demonstrates that TOR and auxin signaling synergistically contribute to alleviating LT damage in cucumber seedlings by exogenous MT. These findings help us understand the function of MT and provide insights into the regulatory network of MT that regulates the LT tolerance of plants.
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Cucumis sativus , Ácidos Indolacéticos , Melatonina , Plântula , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Melatonina/farmacologia , Melatonina/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Ácidos Indolacéticos/metabolismo , Temperatura Baixa , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Serina-Treonina Quinases TOR/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The emergence of carbapenem-resistant bacteria especially carbapenem-resistant Escherichia coli (CREC) in food animals poses a serious threat to food safety and public health. Reports about the dissemination of carbapenem-resistant bacteria along the food animal production chain are scattered and mainly focus on swine and chicken. Abuse of antibiotics in duck farms is common especially in China which has the largest duck production industry, however, the CREC transmission between farmed ducks and slaughtered meats remains unclear and the role of slaughterhouse in disseminating CREC among duck meats remains largely unknown. Herein, we collected 251 fecal samples from five typical duck farms along with 125 slaughtered meat samples (25 from each farm) in the corresponding slaughterhouse in Anhui Province, China, in December 2018. All samples were screened for CREC isolates which were analyzed for the presence of carbapenemase genes and colistin resistance gene mcr. The resistance profiles, transferability, pulsed-field gel electrophoresis (PFGE), whole-genome sequencing and phylogenetic analysis of the CREC isolates from both ducks and meats were further characterized. This is the first report presenting the high prevalence of blaNDM-positive CREC isolates in ducks from duck farms (57.8 %) and slaughtered meats (33.6 %) in the corresponding slaughterhouse. Among the 203 blaNDM-positive CREC isolates obtained in this study, 19.2 % harbored mcr-1 and all CREC isolates showed resistance to nearly all currently available antibiotics (except tigecycline). Of note, mcr-1 was found in 17.8 % of the meat-derived CREC carrying blaNDM. Based on the PFGE analysis, clonal spread of blaNDM-positive CREC including some also carrying mcr-1 was found between farmed ducks and slaughtered duck meats even from different farms. Special attention should be paid to the clonal dissemination of meat-derived CREC within the slaughterhouse, which contributed to the high prevalence of blaNDM in slaughtered meats. Additionally, horizontal transmission mainly mediated by transferable blaNDM-5-bearing IncX3 plasmids, untypable blaNDM-1-bearing plasmids and mcr-1-bearing IncHI2 plasmids further facilitated the rapid spread of such multidrug-resistant strains. Notably, the blaNDM-bearing plasmids and mcr-1-bearing plasmids in CREC from meats were highly similar to those from animals and humans. More worryingly, the phylogenomic analysis showed that CREC isolates from both ducks and corresponding meats clustered with previously reported human CREC isolates carrying mcr-1 in different geographical areas including China. These findings further prove that the CREC and resistance plasmids in farmed ducks could transmit to meats even from different farms via the slaughterhouse and then trigger infections in humans. The high prevalence and clonal transmission of CREC isolates including those also carrying mcr-1 between ducks and meats are alarming, and urgent control measures are required to reduce the dissemination of such organisms.
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Matadouros , Antibacterianos , Patos , Escherichia coli , Carne , beta-Lactamases , Animais , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Carne/microbiologia , China/epidemiologia , Prevalência , beta-Lactamases/genética , Antibacterianos/farmacologia , Inocuidade dos Alimentos , Fazendas , Infecções por Escherichia coli/transmissão , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Filogenia , Fezes/microbiologia , Microbiologia de Alimentos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Proteínas de Escherichia coli/genética , Proteínas de Bactérias/genéticaRESUMO
Background: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals. Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated. Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05). Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.
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BACKGROUND & AIMS: The aim of this study was to investigate the persistence of Lugol-unstained lesions (LULs) in the esophagus detected by chromoendoscopy and explore their association with progression to malignancy. METHODS: We enrolled 647 participants from a population-based screening trial who had biopsied LULs at the baseline chromoendoscopy and underwent a chromoendoscopy reexamination after a median of 4.39 years. Cases of persistent LUL were defined as those in whom a visible LUL was observed during reexamination at the documented location (±2 cm) where a LUL was detected at baseline chromoendoscopy. Logistic regression was applied to explore risk factors for the persistence of LULs. The primary outcome was clinical-stage esophageal squamous cell carcinoma identified over 6.78 years of follow-up, and the secondary outcome was re-examination-detected severe dysplasia and above lesions. The cumulative incidence was calculated to assess the progression risk associated with the persistence of LULs. RESULTS: The proportion of participants with persistent LULs was 81.92%. Dysplasia (adjusted odds ratio [OR], 6.16; 95% confidence interval [CI], 2.70-17.80), large LULs (adjusted OR, 1.90; 95% CI, 1.18-3.15), and irregularly shaped LULs (adjusted OR, 1.63; 95% CI, 1.03-2.56) at baseline were associated with an increased risk of LUL persistence. Eleven clinical-stage esophageal squamous cell carcinoma cases and 31 severe dysplasia and above lesions detected during reexamination were identified, all of which originated from patients with persistent LULs (Pclinical-stage ESCC = .136; Preexamination-detected SDA = .015). CONCLUSION: The persistence of LULs is associated with progression to malignancy in the esophagus, even in individuals without dysplastic lesions. Based on this, a more efficient post-screening surveillance strategy could be established.
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Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 µM, respectively.
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OBJECTIVE: A robotic system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter, prospective, randomized controlled trial (RCT) was to determine whether robotic-arm-assisted TKA improves clinical and radiological outcomes when compared to conventional TKA. METHODS: One hundred and thirty patients who underwent primary TKA were enrolled in this prospective, randomized controlled trial, which was conducted at three hospitals. Five patients were lost to follow-up 6 weeks after surgery. Therefore, 125 participants (63 in the intervention group and 62 in the control group) remained in the final analysis. The primary outcome was the rate at which the mechanical axis of the femur deviated by less than 3° from the mechanical axis of the tibia. This was evaluated by full-length weight-bearing X-rays of the lower limb 6 weeks postoperatively. Secondary outcomes included operation times, 6-week postoperative functional outcomes evaluated by the American Knee Society score (KSS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), short form-36 (SF-36) health survey results, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: At 6 weeks postoperatively, we found that the rate of radiographic inliers was significantly higher in the intervention group (78.7% vs 51.6%; p = 0.00; 95% confidence interval, 10.9% to 43.2%). The operation was significantly longer in the intervention group than in the control group (119.5 vs 85.0 min; p = 0.00). There were no significant differences in the 6-week postoperative functional outcomes, SF-36, AEs, and SAEs between the two groups. There were no AEs or SAEs that were determined to be "positively related" to the robotic system. CONCLUSION: Robotic-arm-assisted TKA is safe and effective, as demonstrated in this trial.
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OBJECTIVE: To analyze the relationship between serum cystatin C (CysC), ß2-microglobulin (ß2-MG) and the efficacy of demethylation therapy in patients with acute myeloid leukemia (AML). METHODS: A prospective cohort study was conducted on 98 AML patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from February 2019 to January 2022. All patients were treated with decitabine (DAC) + HAG regimen, 28 days as a course and treated for 3-4 courses. At the end of each course of treatment, the treatment effect of the patients was evaluated, and the patients who achieved complete remission (CR) transferred to consolidation therapy, while the patients who did not reach CR at the end of the course of treatment were considered as treatment failure. The examination items before treatment include routine blood parameters, serum CysC, and ß2-MG, and general clinical data of the patients were collected. According to the statistical results, logistic regression model was used to analyze the relationship between serum CysC, ß2-MG and the efficacy of demethylation therapy in AML patients. The ROC curves were drawn, and the predictive efficacy of serum CysC, ß2-MG on demethylation therapy in AML patients was evaluated by the area under the curve (AUC). RESULTS: Of the 98 AML patients enrolled in the study, 5 cases were excluded during the treatment period, and 93 cases finally completed the chemotherapy courses. Among them, 23 patients achieved CR after the initial induction chemotherapy (course 1-2), and 11 patients achieved CR after the re-induction chemotherapy (course 3-4). The success rate of demethylation therapy was 36.56 % (34/93). Compared with the patients in treatment success group, patients in treatment failure group had a higher proportion of intermediate- and adverse-risk, lower levels of platelet (PLT) and hemoglobin (Hb), and higher expression levels of serum CysC and ß2-MG, all of which were statistically significant (P < 0.05). Logistic regression analysis showed that high expression of serum CysC, ß2-MG and adverse-risk were independent risk factors for failure of demethylation treatment in AML patients (OR >1, P < 0.05). The ROC curves showed that the AUC values of serum CysC, ß2-MG alone and combined in predicting the efficacy of demethylation therapy in AML patients were 0.788, 0.785 and 0.834, respectively. CONCLUSION: The failure of demethylation therapy in AML patients is related to the high expression of serum CysC and ß2-MG, and detection of serum CysC and ß2-MG before treatment can predict the risk of demethylation therapy failure in AML patients.
Assuntos
Cistatina C , Leucemia Mieloide Aguda , Microglobulina beta-2 , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/sangue , Estudos Prospectivos , Microglobulina beta-2/sangue , Cistatina C/sangue , Desmetilação , Indução de Remissão , Decitabina , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-IdadeRESUMO
The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.
Assuntos
Diferenciação Celular , Proteína 3 de Resposta de Crescimento Precoce , Melanoma , Células de Schwann , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Proteína 3 de Resposta de Crescimento Precoce/genética , Proteína 3 de Resposta de Crescimento Precoce/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Melanoma/genética , Células de Schwann/metabolismoRESUMO
T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8-/- mice received DCPC daily by transiently inhaling 10% CO2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8-/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8-/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC.