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Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation. Through this approach, we identified a candidate proteolysis-targeting chimera (PROTAC), 22-SLF, that induces the degradation of FK506-binding protein 12 when the transcription of FBXO22 gene is activated. Subsequent mechanistic investigations revealed that 22-SLF interacts with C227 and/or C228 in F-box protein 22 (FBXO22) to achieve target degradation. Lastly, we demonstrated the versatility of FBXO22-based PROTACs by effectively degrading additional endogenous proteins, including bromodomain-containing protein 4 and the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein.
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Brassinazole resistant 1 (BZR1), a brassinosteroid (BR) signaling component, plays a pivotal role in regulating numerous specific developmental processes. Our study demonstrated that exogenous treatment with 2,4-epibrassinolide (EBR) significantly enhanced the accumulation of carotenoids and chlorophylls in Chinese kale (Brassica oleracea var. alboglabra). The underlying mechanism was deciphered through yeast one-hybrid (Y1H) and dual-luciferase (LUC) assays, whereby BoaBZR1.1 directly interacts with the promoters of BoaCRTISO and BoaPSY2, activating their expression. This effect was further validated through overexpression of BoaBZR1.1 in Chinese kale calli and plants, both of which exhibited increased carotenoid accumulation. Additionally, qPCR analysis unveiled upregulation of carotenoid and chlorophyll biosynthetic genes in the T1 generation of BoaBZR1.1-overexpressing plants. These findings underscored the significance of BoaBZR1.1-mediated BR signaling in regulating carotenoid accumulation in Chinese kale and suggested the potential for enhancing the nutritional quality of Chinese kale through genetic engineering of BoaBZR1.1.
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Background: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC. Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI. Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells. Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy.
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Since the COVID-19, cough sounds have been widely used for screening purposes. Intelligent analysis techniques have proven to be effective in detecting respiratory diseases. In 2021, there were up to 10 million TB-infected patients worldwide, with an annual growth rate of 4.5%. Most of the patients were from economically underdeveloped regions and countries. The PPD test, a common screening method in the community, has a sensitivity of as low as 77%. Although IGRA and Xpert MTB/RIF offer high specificity and sensitivity, their cost makes them less accessible. In this study, we proposed a feature fusion model-based cough sound classification method for primary TB screening in communities. Data were collected from hospitals using smart phones, including 230 cough sounds from 70 patients with TB and 226 cough sounds from 74 healthy subjects. We employed Bi-LSTM and Bi-GRU recurrent neural networks to analyze five traditional feature sets including the Mel frequency cepstrum coefficient (MFCC), zero-crossing rate (ZCR), short-time energy, root mean square, and chroma_cens. The incorporation of features extracted from the speech spectrogram by 2D convolution training into the Bi-LSTM model enhanced the classification results. With traditional futures, the best TB patient detection result was achieved with the Bi-LSTM model, with 93.99% accuracy, 93.93% specificity, and 92.39% sensitivity. When combined with a speech spectrogram, the classification results showed 96.33% accuracy, 94.99% specificity, and 98.13% sensitivity. Our findings underscore that traditional features and deep features have good complementarity when fused using Bi LSTM modelling, which outperforms existing PPD detection methods in terms of both efficiency and accuracy.
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Tosse , Redes Neurais de Computação , Tuberculose Pulmonar , Humanos , Tosse/diagnóstico , Tuberculose Pulmonar/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , COVID-19/diagnóstico , Idoso , Sensibilidade e EspecificidadeRESUMO
Background: Imbalance in intestinal microbiota caused by microbial species and proportions or metabolites derived from microbes are associated with hypertension, as well as diabetic nephropathy. However, the involvement of the intestinal microbiota and metabolites in hypertension and diabetic nephropathy comorbidities (HDN) remains to be elucidated. Methods: We investigated the effects of intestinal microbiota on HDN in a rat model and determined the abundance of the intestinal microbiota using 16S rRNA sequencing. Changes in fecal and serum metabolites were analyzed using ultra-high-performance liquid chromatography-mass spectrometry. Results: The results showed abundance of Proteobacteria and Verrucomicrobia was substantially higher, whereas that of Bacteroidetes was significant lower in the HDN group than in the sham group. Akkermansia, Bacteroides, Blautia, Turicibacter, Lactobacillus, Romboutsia, and Fusicatenibacter were the most abundant, and Prevotella, Lachnospiraceae_NK4A136_group, and Prevotella_9 were the least abundant in the HDN group. Further analysis with bile acid metabolites in serum showed that Blautia was negatively correlated with taurochenodeoxycholic acid, taurocholic acid, positively correlated with cholic acid and glycocholic acid in serum. Conclusions: These findings suggest that the gut microbiota and metabolites in feces and serum substantially differed between the HDN and sham groups. The F/B ratio was higher in the HDN group than in the sham group. Blautia is potentially associated with HDN that correlated with differentially expressed bile acid metabolites, which might regulate the pathogenesis of HDN via the microorganism-gut-metabolite axis.
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Machine learning has been increasingly used to retrieve chlorophyll-a (Chl-a) in optically variable waters. However, without the guidance of physical principles or expert knowledge, machine learning may produce biased mapping relationships, or waste considerable time searching for physically infeasible hyperparameter domains. In addition, most Chl-a retrieval models cannot evaluate retrieval uncertainty when ground observations are not available, and the retrieval uncertainty is crucial for understanding the model limitations and evaluating the reliability of retrieval results. In this study, we developed a novel knowledge-guided mixture density network to retrieve Chl-a in optically variable inland waters based on Sentinel-3 Ocean and Land Color Instrument (OLCI) imagery. The proposed method embedded prior knowledge derived from spectral shape classification into the mixture density network. Compared to another deterministic model, the knowledge-guided mixture density network outputted the conditional distribution of Chl-a given an input spectrum, enabling us to estimate the optimal retrieval and the associated uncertainty. The proposed method showed favorable correspondence with the field Chl-a, with root mean square error (RMSE) of 6.56 µg/L, and mean absolute percentage error (MAPE) of 43.64 %. Calibrated against Sentinel-3 OLCI spectrum, the proposed method also performed well when applied to field spectrum (RMSE = 4.58 µg/L, MAPE = 72.70 %), suggesting its effectiveness and good generalization. The proposed method provided the standard deviation of each estimated Chl-a, which enabled us to inspect the reliability of the estimated results and understand the model limitations. Overall, the proposed method improved the Chl-a retrieval in terms of model accuracy and uncertainty evaluation, providing a more comprehensive Chl-a observation of inland waters.
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Melatonin, a pleiotropic small molecule, is employed in horticultural crops to delay senescence and preserve postharvest quality. In this study, 100 µM melatonin treatment delayed a decline in the color difference index h* and a*, maintaining the content of chlorophyll and carotenoids, thereby delaying the yellowing and senescence of Chinese kale. Transcriptome analysis unequivocally validates melatonin's efficacy in delaying leaf senescence in postharvest Chinese kale stored at 20 °C. Following a three-day storage period, the melatonin treatment group exhibited 1637 differentially expressed genes (DEGs) compared to the control group. DEG analysis elucidated that melatonin-induced antisenescence primarily governs phenylpropanoid biosynthesis, lipid metabolism, plant signal transduction, and calcium signal transduction. Melatonin treatment up-regulated core enzyme genes associated with general phenylpropanoid biosynthesis, flavonoid biosynthesis, and the α-linolenic acid biosynthesis pathway. It influenced the redirection of lignin metabolic flux, suppressed jasmonic acid and abscisic acid signal transduction, and concurrently stimulated auxin signal transduction. Additionally, melatonin treatment down-regulated RBOH expression and up-regulated genes encoding CaM, thereby influencing calcium signal transduction. This study underscores melatonin as a promising approach for delaying leaf senescence and provides insights into the mechanism of melatonin-mediated antisenescence in postharvest Chinese kale.
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Brassica , Melatonina , Humanos , Brassica/genética , Brassica/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Senescência Vegetal , Cálcio/metabolismo , Atraso no Tratamento , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , TranscriptomaRESUMO
A novel Gram-positive strain WQ 127069T that was isolated from the soil of Baima Snow Mountain, a habitat of highly endangered Yunnan snub-nosed monkeys (Rhinopithecus bieti), was subjected to a polyphasic taxonomic study. Phylogenetic analysis based on the 16S rRNA gene sequences showed that the isolate belongs to the genus Paenibacillus, showing 98.4 and 96.08â% sequence similarity to the type strains Paenibacillus periandrae PM10T and Paenibacillus foliorum LMG 31456T, respectively. The G+C content of the genomic DNA of strain WQ127069T was 45.6 mol%. The predominant isoprenoid quinone was MK-7, and meso-diaminopimelic acid was present in peptidoglycan. The major cellular fatty acids were antiiso-C15â:â0, iso-C15â:â0 and C16â:â0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylmonomethylethanolamine. The whole genome average nucleotide identity and digital DNA-DNA hybridization values between strain WQ 127069T and strain PM10T were 93.2 and 52.5â%, respectively. Growth occurred at 5-40â°C (optimally at 20-35â°C), pH 6-8 (optimally at pH7.0) and with 0.5-2â% (w/v) NaCl (optimally at 0.5â%). On the basis of the taxonomic evidence, a novel species, Paenibacillus baimaensis sp. nov., is proposed. The type strain is WQ 127069T (=KCTC 43480T=CCTCC AB 2022381T).
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Paenibacillus , Presbytini , Animais , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Solo , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , China , EcossistemaRESUMO
The pleiotropic effects of TGR5 make it an appealing target for intervention of metabolic and inflammatory disorders, but systemic activation of TGR5 faces challenges of on-target side effects, especially gallbladder filling. Gut-restricted agonists were proved to be sufficient to circumvent these side effects, but extremely low systemic exposure may not be effective in activating TGR5 since it is located on the basolateral membrane. Herein, to balance potency and physicochemical properties, a series of gut-restricted TGR5 agonists with diversified kinetophores had been designed and synthesized. Compound 22-Na exhibited significant antidiabetic effect, and showed favorable gallbladder safety after 7 days of oral administration in humanized TGR5H88Y mice, confirming that gut-restricted agonism of TGR5 is a viable strategy to alleviate systemic target-related effects.
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Ácido Betulínico , Receptores Acoplados a Proteínas G , Camundongos , Animais , Receptores Acoplados a Proteínas G/metabolismo , Hipoglicemiantes/farmacologia , Vesícula Biliar/metabolismoRESUMO
Fabricating an efficient electrocatalyst for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) isthe most challenging task for overall water splitting. Herein, we utilized the confinement effect of molten sodium chloride (NaCl) to controllably prepare hollow Co/Co3O4 nanoparticles embedded into nitrogen-doped carbon (H-Co/Co3O4-NC). Experimental and theoretical investigations revealed that the interfacial interaction within Co/Co3O4 heterostructure played a pivotal role in modulating the electronic structure and facilitating the electron transfer. Meanwhile, the superiority of hollow nanostructure could promote the mesoscale mass diffusion. Remarkably, the as-prepared H-Co/Co3O4-NC catalyst achieved the low overpotentials of 316 mV and 252 mV towards OER and HER, respectively, which delivered overall water splitting with the potential of 1.76 V at a current density of 10 mA cm-2.
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Simultaneous detection of multiple foodborne pathogens is of great importance for ensuring food safety. Herein, we present a sensitive dual-channel electrochemical biosensor based on copper metal organic frameworks (CuMOF) and lead metal organic framework (PbMOF) for simultaneous detection of Salmonella typhimurium (S. typhimurium) and Listeria monocytogenes (L. monocytogenes). The MOF-based nanotags were prepared by functionalizing gold nanoparticles loaded CuMOF (Au@CuMOF) and PbMOF (Au@PbMOF) with signal DNA sequences 1 (sDNA1) and sDNA2, respectively. By selecting invA of S. typhimurium and inlA gene of L. monocytogenes as targe sequences, a sandwich-typed dual-channel biosensor was developed on glassy carbon electrodes (GCE) through hybridization reactions. The sensitive detection of S. typhimurium and L. monocytogenes was achieved by the direct differential pulse voltametric (DPV) signals of Cu2+ and Pb2+. Under optimal conditions, channel 1 of the biosensor showed linear range for invA gene of S. typhimurium in 1 × 10-14-1 × 10-8 M with low detection limit (LOD) of 3.42 × 10-16 M (S/N = 3), and channel 2 of the biosensor showed linear range for inlA gene of L. monocytogenes in 1 × 10-13-1 × 10-8 M with LOD of 6.11 × 10-15 M (S/N = 3). The dual-channel biosensor showed good selectivity which were used to detect S. typhimurium with linear range of 5-1.0 × 104 CFU mL-1 (LOD of 2.33 CFU mL-1), and L. monocytogenes with linear range of 10 - 1.0 × 104 CFU mL-1 (LOD of 6.61 CFU mL-1).
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Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , Ouro , Salmonella typhimurium , Limite de DetecçãoRESUMO
Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. This expansion will broaden the scope of potential protein targets, accommodating those with varying subcellular localizations and expression patterns. In this study, we describe a CRISPR-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation. This approach allows us to address the limitations associated with investigating candidate degrader molecules in specific cell lines that either lack or have low levels of the desired E3 ligases. Through this approach, we identified a candidate proteolysis-targeting chimera (PROTAC), 22-SLF, that induces the degradation of FKBP12 when the FBXO22 gene transcription is activated. 22-SLF induced the degradation of endogenous FKBP12 in a FBXO22-dependent manner across multiple cancer cell lines. Subsequent mechanistic investigations revealed that 22-SLF interacts with C227 and/or C228 in FBXO22 to achieve the target degradation. Finally, we demonstrated the versatility of FBXO22-based PROTACs by effectively degrading another endogenous protein BRD4. This study uncovers FBXO22 as an E3 ligase capable of supporting ligand-induced protein degradation through electrophilic PROTACs. The platform we have developed can readily be applied to elucidate protein degradation pathways by identifying E3 ligases that facilitate either small molecule-induced or endogenous protein degradation.
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Sepsis, a life-threatening condition caused by an inflammatory response to systemic infection, results in a significant social burden and healthcare costs. This study aimed to investigate the relationship between the C-reactive protein (CRP) trajectories of patients with sepsis in the intensive care unit (ICU) and the in-hospital mortality rate. We reviewed 1464 patients with sepsis treated in the ICU of Dongyang People's Hospital from 2010 to 2020 and used latent growth mixture modeling to divide the patients into four classes according to CRP trajectory (intermediate, gradually increasing, persistently high, and persistently low CRP levels). We found that patients with intermediate and persistently high CRP levels had the lowest (18.1%) and highest (32.6%) in-hospital mortality rates, respectively. Multiple logistic regression analysis showed that patients with persistently high (odds ratio [OR] = 2.19, 95% confidence interval [CI] = 1.55-3.11) and persistently low (OR = 1.41, 95% CI = 1.03-1.94) CRP levels had a higher risk of in-hospital mortality than patients with intermediate CRP levels. In conclusion, in-hospital mortality rates among patients with sepsis differ according to the CRP trajectory, with patients with intermediate CRP levels having the lowest mortality rate. Further research on the underlying mechanisms is warranted.
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Proteína C-Reativa , Sepse , Humanos , Mortalidade Hospitalar , Estado Terminal , Custos de Cuidados de SaúdeRESUMO
Objectives: The aim is to evaluate the effect of a novel 14-day fasting regimen on the balance between skeletal muscle and adipose tissue composition which might associate with inflammatory factors. Our analysis includes basic physical examinations, clinical laboratory analysis, bioelectrical impedance and biochemical analytic assessments of healthy volunteers. Methods: Eight healthy subjects were randomly selected from a pool of volunteers to undergo a continual dietary deprivation (CDD) regimen. Individuals were assigned to take Flexible Abrosia (FA, prebiotic combination) plus appropriate mineral supplement of potassium and magnesium at 3 mealtime every day to prevent potential injury from starved intestinal flora and avoid spasms of smooth muscle due to hunger. Physical and medical examinations were conducted and blood samples were collected at following timepoints: before CDD as self-control (0D), day 7 and day 14 during fasting, and 7-21days and/or 2~3mo after refeeding. Results: The combination of FA and mineral supplements significantly decreased self-reported physical response of starvation, with tolerable hunger-mediated sensations experienced during CDD. Bioelectrical and biochemical results indicated significant reduction in both muscle lean and fat mass on day 7. Meanwhile, markers related to fat composition consistently decreased during and after CDD. In addition, most biochemical marker levels, including serum proteins, reached their inflection points at the 7th day of CDD as compared to the control measurements. Levels of these factors started to show a relative plateau, or reversed direction upon the 14th day of CDD. The exceptions of above factors were myostatin and complement protein C3, which remained at lower concentrations in the blood throughout CDD, and were unable to fully recover toward baseline levels even after 3 months' refeeding. Conclusion: Our results indicated that human subjects undergoing prolonged dietary restriction were well protected by FA and mineral ions from gut injury or physical discomfort of starvation. Most factors showed a relative plateau response at the end of 14D-CDD. The muscle tissues were well preserved during prolonged fasting, and an improved protein/lipid ratio was observed. Upon refeeding, constant lower levels of myostatin and complement C3 were maintained after CDD implies a long-term beneficial effect in dealing with anti-aging and inflammation.
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Miostatina , Inanição , Humanos , Complemento C3 , Regulação para Baixo , Jejum , DietaRESUMO
Malabar spinach (Basella alba), amaranth (Amaranthus tricolor), and sweet potato (Ipomoea batatas) are leafy vegetables found in Southwest China. The variation of chlorophyll, carotenoids, ascorbic acid, total flavonoids, phenolic compounds, and antioxidant capacity was studied in the leaves and stems of the three vegetables. The content of main health-promoting compounds and the antioxidant capacity in the leaves were higher than that in the stems, indicating that the leaves of the three vegetables possess greater nutritional value. The trend of total flavonoids in all three vegetables was similar to the trend of antioxidant capacity, suggesting that the total flavonoids may be the major antioxidants wihin these vegetables. Eight individual phenolic compounds were detected in three different vegetables. The most abundant levels of individual phenolic compounds in the leaves and stems of malabar spinach, amaranth, and sweet potato were 6'-O-feruloyl-d-sucrose (9.04 and 2.03 mg g-1 DW), hydroxyferulic acid (10.14 and 0.73 mg g-1 DW), and isorhamnetin-7-O-glucoside (34.93 and 6.76 mg g-1 DW), respectively. Sweet potato exhibited a higher total and individual phenolic compound content compared to malabar spinach and amaranth. Overall, the results demonstrate that the three leafy vegetables possess high nutritional value, and could be used not only for consumption but also in various other fields, including medicine and chemistry.
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Antioxidantes , Verduras , Antioxidantes/química , Verduras/química , Flavonoides/análise , Ácido Ascórbico/análise , Fenóis/análise , Folhas de Planta/químicaRESUMO
Chinese kale is a widely cultivated plant in the genus Brassica in the family Brassicaceae. The origin of Brassica has been studied extensively, but the origin of Chinese kale remains unclear. In contrast to Brassica oleracea, which originated in the Mediterranean region, Chinese kale originated in southern China. The chloroplast genome is often used for phylogenetic analysis because of its high conservatism. Fifteen pairs of universal primers were used to amplify the chloroplast genomes of white-flower Chinese kale (Brassica oleracea var. alboglabra cv. Sijicutiao (SJCT)) and yellow-flower Chinese kale (Brassica oleracea var. alboglabra cv. Fuzhouhuanghua (FZHH)) via PCR. The lengths of the chloroplast genomes were 153,365 bp (SJCT) and 153,420 bp (FZHH) and both contained 87 protein-coding genes and eight rRNA genes. There were 36 tRNA genes in SJCT and 35 tRNA genes in FZHH. The chloroplast genomes of both Chinese kale varieties, along with eight other Brassicaceae, were analyzed. Simple sequence repeats, long repeats, and variable regions of DNA barcodes were identified. An analysis of inverted repeat boundaries, relative synonymous codon usage, and synteny revealed high similarity among the ten species, albeit the slight differences that were observed. The Ka/Ks ratios and phylogenetic analysis suggest that Chinese kale is a variant of B. oleracea. The phylogenetic tree shows that both Chinese kale varieties and B. oleracea var. oleracea were clustered in a single group. The results of this study suggest that white and yellow flower Chinese kale comprise a monophyletic group and that their differences in flower color arose late in the process of artificial cultivation. Our results also provide data that will aid future research on genetics, evolution, and germplasm resources of Brassicaceae.
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Brassica , Genoma de Cloroplastos , Brassica/genética , Filogenia , Análise de Sequência de DNA , FloresRESUMO
OBJECTIVE: To assess the postoperative quality of life and prognosis of patients with intracranial aneurysm (IA) after nursing based on a time-based concept. METHODS: Data of 84 patients with IA who underwent treatment at the Shengjing Hospital Affiliated to China Medical University from February 2019 to February 2021 were analyzed retrospectively. Among them, the control group (n=41) received conventional nursing. On this basis, the observation group (n=43) received nursing based on the concept of time. Patients' limb motor function and quality of life before and after treatment, postoperative complications and prognosis, and nursing satisfaction were evaluated. Also, risk factors for poor prognosis were analyzed through multifactorial analysis. RESULTS: One month after surgery, the scores of Fugl-Meyer Assessment (FMA) and Quality-of-Life Questionnaire Core in both groups were higher than those before nursing, and both scores were dramatically higher in the observation group than in the control group (P<0.05). The overall postoperative complication rate was markedly higher in the control group than in the observation group (P<0.05). Patients in the observation group were more satisfied with the nursing than those in the control group (P<0.05). The postoperative prognosis in the observation group was dramatically better than that in the control group (P<0.05). There were statistical differences in age, timing of intervention, hypertension, aneurysm diameter, Hunt-Hess classification, Fisher grade, FMA score and nursing regimen at one month postoperatively between the good prognosis group and the poor prognosis group (P<0.05). Older age, delayed timing of intervention, aneurysm ≥15 mm and Fisher grade ≥3 were independent risk factors for poor prognosis. CONCLUSION: In summary, a nursing model based on the concept of time can effectively improve the rehabilitation outcome, improve the prognosis, and enhance the quality of life in IA patients.
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Background: Direct antihypertensive therapy in hypertensive patients with a high CVD risk can reduce the incidence of cardiovascular death but increase adverse cardiovascular events, so additional ways to identify hypertensive patients at high risk may be needed. Studies have shown that immunity and inflammation affect the prognoses of patients with hypertension and that the pan-immune-inflammation value (PIV) is an index to assess immunity and inflammation, but few studies have applied the PIV index to patients with hypertension. Objective: To explore the relationship between the PIV and long-term all-cause and cardiovascular mortality in patients with hypertension. Method: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 with a mortality follow-up through December 31, 2019, were analyzed. A total of 26,781 participants were evaluated. The patients were grouped based on PIV levels as follows: T1 group (n = 8,938), T2 group (n = 8,893), and T3 group (n = 8,950). The relationship between the PIV and long-term all-cause and cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights. Result: The PIV was significantly associated with long-term all-cause and cardiovascular mortality in patients with hypertension. After full adjustment, patients with higher PIV have a higher risk of all-cause [Group 3: HR: 1.37, 95% CI: 1.20-1.55, p < 0.001] and cardiovascular [Group 3: HR: 1.62, 95% CI: 1.22-2.15, p < 0.001] mortality. Conclusion: Elevated PIV was associated with increased all-cause mortality and cardiovascular mortality in hypertensive patients.
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Considerable evidence shows that oxidative stress exists in the pathophysiological process of female reproductive system diseases. At present, there have been many studies on oxidative stress of placenta during pregnancy, especially for preeclampsia. However, studies that directly focus on the effects of oxidative stress on blood vessels at the maternal-fetal interface and their associated possible outcomes are still incomplete and ambiguous. To provide an option for early clinical prediction and therapeutic application of oxidative stress in female reproductive system diseases, this paper briefly describes the composition of the maternal-fetal interface and the molecular mediators produced by oxidative stress, focuses on the sources of oxidative stress and the signaling pathways of oxidative stress at the maternal-fetal interface, expounds the adverse consequences of oxidative stress on blood vessels, and deeply discusses the relationship between oxidative stress and some pregnancy complications and other female reproductive system diseases.
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Doenças dos Genitais Femininos , Pré-Eclâmpsia , Complicações na Gravidez , Gravidez , Feminino , Humanos , Estresse Oxidativo/fisiologia , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Pré-Eclâmpsia/metabolismo , Genitália Feminina/metabolismoRESUMO
Background: Liposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment. Case presentation: A 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1-14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months. Conclusion: This case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy.