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Background: The effectiveness of coronary computed tomography (CT) angiography in assessing stent restenosis is hindered by heavy metal artifacts. This study aimed to evaluate the image quality of monoenergetic reconstructions and iodine density map for coronary stent imaging using an 8-cm dual-layer detector spectral CT. Methods: In this study, 8 stents with a diameter <3 mm (group A) and 10 with a diameter ≥3 mm (group B) were placed in plastic tubes filled with iodinated contrast media and scanned. The internal diameter of the prepared stents was then measured by intravascular ultrasound. The reconstructed images included iodine density maps, conventional images, and different energy levels. The visualization of the stent lumen and stent structure was subjectively assessed using a 4-point Likert scale. The objective evaluation was performed using the in-stent lumen signal-to-noise ratio (SNRis), non-stent lumen SNR (SNRns), internal diameter difference (IDD), and blooming artifact index (BAI). The Friedman test and analysis of variance were used for multiple comparisons. Results: For lumen visualization, the optimal monoenergetic images received the highest score for both group A (2.56±0.51) and group B (3.1±0.55). Multiple comparisons showed that there were significant differences between the optimal monoenergetic images and iodine density maps. However, for stent structure, iodine density maps received the highest score for group A (3.0±0.52) and group B (3.8±0.41). For quantitative assessment, the optimal monoenergetic images had the highest SNRis and SNRns, while the iodine density maps had the lowest SNRis and SNRns. For IDD and BAI, the iodine density maps yielded the smallest value. Conclusions: The monoenergetic images on the second-generation dual-layer detector CT provide better visualization of the lumen and higher SNR. However, iodine density maps are superior for evaluating stent structure and IDD and BAI compared to monoenergetic and conventional reconstructions.
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The regulation of the mammalian circadian clock is largely dependent on heredity. In model animals for circadian rhythm studies, C57BL/6 and BALB/c mice exhibit considerable differences in their adaptation to circadian disruption, yet deeper comparisons remain unexplored. Here, we have established embryonic fibroblast cells derived from C57BL/6 mice (MEF) and BALB/c (BALB/3T3) mice, which have been transfected with the Bmal1 promoter-driven luciferase (Bmal1-Luc) reporter gene. Next, dexamethasone was applied for various cyclic stimulations, which revealed that Bmal1 bioluminescence of MEF cells was entrained to 24 to 26 h cycles, whereas BALB/3T3 cells have a wider range (22 to 28 h) with lower amplitudes. Behaviorally, BALB/c mice swiftly adapted to a 6-h advance light/dark cycle, unlike C57BL/6 mice. Furthermore, we found the expression of the circadian rhythm gene Npas2 in BALB/c mice is significantly lower than that in C57BL/6 mice. This observation is consistent with the differentially expressed genes (DEGs) in the intestine and lung tissues of C57BL/6 and BALB/c mice, based on the RNA-seq datasets downloaded from the Gene Expression Omnibus (GEO). In summary, our study uncovers that BALB/c mice possess greater resilience in circadian rhythm than C57BL/6 mice, both cellular and behaviorally, identifying potential genes underlying this difference.
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Fatores de Transcrição ARNTL , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Relógios Circadianos , Ritmo Circadiano , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Animais , Camundongos , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Relógios Circadianos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fibroblastos/metabolismo , Fotoperíodo , Comportamento Animal , Dexametasona/farmacologia , Especificidade da Espécie , Adaptação Fisiológica/genética , Células 3T3 BALB , Proteínas do Tecido NervosoRESUMO
With the escalating crisis of bacterial multidrug resistance, anti-virulence therapeutic strategies have emerged as a highly promising alternative to conventional antibiotic treatments. Anti-virulence compounds are specifically designed to target virulence factors (VFs), disarming pathogens without affecting bacterial growth and thus reduce the selective pressure for resistance development. However, due to the complexity of bacterial pathogenesis, no anti-virulence small molecules have been approved for clinical use thus far, despite the documentation of hundreds of potential candidates. To provide valuable reference resources for drug design, repurposing, and target selection, the virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) has systematically collected public data on anti-virulence compounds through extensive literature mining, and further integrated this information with its existing knowledge of bacterial VFs. To date, the VFDB has curated a comprehensive dataset of 902 anti-virulence compounds across 17 superclasses reported by 262 studies worldwide. By cross-linking the current knowledge of bacterial VFs with information on relevant compounds (e.g. classification, chemical structure, molecular targets and mechanisms of action), the VFDB aims to bridge the gap between chemists and microbiologists, providing crucial insights for the development of innovative and effective antibacterial therapies to combat bacterial infections and address antibiotic resistance.
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BACKGROUND: Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS: In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS: 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION: The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING: Akeso Biopharma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Recidiva Local de Neoplasia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Pessoa de Meia-Idade , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , China , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Adulto Jovem , Adolescente , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Intervalo Livre de ProgressãoRESUMO
The association between vitamin D concentrations and the occurrence of diabetic foot ulcers (DFUs) remains a topic of ongoing debate. In order to provide a comprehensive and updated review, we conducted this meta-analysis to further investigate the relationship between vitamin D concentrations and DFUs occurrence. The following databases, including Cochrane Library, EMBASE, Web of Science, PubMed, CBM, CNKI, WANFANG DATA and VIP Database, were systematically searched for studies published up to Dec. 20th, 2023. The combined estimation was calculated using both fixed-effects and random-effects models. The overall effect size was reported as a weighted mean difference (WMD) with a corresponding 95% confidence interval (95%CI). Data analysis was performed utilizing Review Manager 5.4 and Stata 14. The Protocol has been registered in PROSPERO CRD42024503468. This updated meta-analysis, incorporating thirty-six studies encompassing 11,298 individuals with or without DFUs, demonstrated a significant association between vitamin D deficiency/insufficiency and an elevated risk of DFUs occurrence (< 25 nmol/L, OR 3.28, P < 0.00001; < 50 nmol/L, OR 2.25, P < 0.00001; < 75 nmol/L, OR 1.67, P = 0.0003). Vitamin D concentrations were significantly lower in individuals with DFUs compared to those without DFUs (P < 0.00001). Subgroup analyses consistently demonstrated this trend among the older population (> 50 years, P < 0.00001), individuals with long duration of diabetes (> 10 years, P < 0.00001), and those with poor glycemic control (mean HbA1c 8%-9% and > 9%, P < 0.00001).
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Pé Diabético , Deficiência de Vitamina D , Vitamina D , Humanos , Pé Diabético/sangue , Pé Diabético/epidemiologia , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/complicaçõesRESUMO
As the core of modern energy technology, lithium-ion batteries (LIBs) have been widely integrated into many key areas, especially in the automotive industry, particularly represented by electric vehicles (EVs). The spread of LIBs has contributed to the sustainable development of societies, especially in the promotion of green transportation. However, the high demand for battery performance and safety in these fields has made the high viscosity, volatility, and potential leakage inherent in traditional organic liquid electrolytes a constraint on their further expansion. Especially at low temperature, the increased viscosity of the electrolyte, reduced solubility of lithium salts, crystallization or solidification of the electrolyte, increased resistance to charge transfer due to interfacial by-products, and short-circuiting due to the growth of anode lithium dendrites all affect the performance and safety of LIBs. Therefore, improving the safety performance of LIBs under low-temperature environments has become a focus of current research. This paper primarily reviews the progress made in utilizing different types of electrolytes in LIBs to enhance safety and optimize low temperature performance and discusses the current research progress as well as the future development direction of the field.
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A simple button press towards a prime stimulus enhances subsequent visual search for objects that match the prime. The present study investigated whether this action effect is a general phenomenon across different task domains, and the underlying neural mechanisms. The action effect was measured in an unspeeded size-matching task, with the presentation of the central target and the surrounding inducers of the Ebbinghaus illusion together to one eye or separately to each eye, and when repetitive TMS was applied over right primary motor cortex (M1). The results showed that a prior key-press significantly reduced the illusion effect compared to passive viewing. Notably, the action effect persisted with dichoptic presentation of the Ebbinghaus configuration, but disappeared with the right M1 disruption. These results suggest that action guides visual perception to influence human behavior, which mainly affects the late visual processing stage and probably relies on feedback projections from the motor cortex.
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Córtex Motor , Desempenho Psicomotor , Percepção de Tamanho , Estimulação Magnética Transcraniana , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Córtex Motor/fisiologia , Percepção de Tamanho/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Estimulação LuminosaRESUMO
In order to address the increasingly prominent issues of water resource protection and agricultural non-point source pollution in the Erhai Lake Basin, this study conducted a two-year field experiment in Gusheng Village, located in the Erhai Lake Basin. In 2022, two irrigation treatments were set up: conventional flooding irrigation (CK) and controlled irrigation (C), with three replicates for each treatment. In 2023, aiming to enhance the utilization rate of rainwater resources and reduce the direct discharge of dry-farming tailwater from upstream into Erhai Lake. The paddy field was used as an ecological storage basin, and the water storage depth of the paddy field was increased compared to the depth of 2022. Combined with the deep storage of rainwater, the dry-farming tailwater was recharged into the paddy field to reduce the drainage. In 2023, two water treatments, flooding irrigation with deep storage and controlled drainage (CKCD) and water-saving irrigation with deep storage and controlled drainage (CCD) were set up, and each treatment was set up with three replicates. The growth and physiological index of rice at various stages were observed. Nitrogen leaching of paddy field in surface water, soil water, and groundwater under different water treatments after tillering fertilizer were observed. The research results show that the combined application of organic and inorganic fertilizers under organic planting can provide more reasonable nutrient supply for rice, promote dry matter accumulation and other indices, and also reduce the concentration of NH4+-N in surface water. Compared with CK, the yield, 1000-grain weight, root-to-shoot ratio, and leaf area index of C are increased by 4.8%, 4.1%, 20.9%, and 9.7%, respectively. Compared with CKCD, the yield, 1000-grain weight, root-to-shoot ratio, and leaf area index of CCD are increased by 6.5%, 3.8%, 19.6%, and 21.9%, respectively. The yield in 2023 is 19% higher than that in 2022. Treatment C can increase the growth indicators and reduce the net photosynthetic rate to a certain extent, while CCD rain-flood storage can alleviate the inhibition of low irrigation lower limit on the net photosynthetic rate of rice. Both C and CCD can reduce nitrogen loss and irrigation amount in paddy fields. CCD can reduce the tailwater in the Gusheng area of the Erhai Lake Basin to Erhai Lake, and also can make full use of N, P, and other nutrients in the tailwater to promote the formation and development of rice. In conclusion, the paddy field rain-flood storage methodology in the Erhai Lake Basin can promote various growth and physiological indicators of rice, improve water resource utilization efficiency, reduce direct discharge of tailwater into Erhai Lake, and decrease the risk of agricultural non-point source pollution.
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Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.
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Cisplatino , Resistencia a Medicamentos Antineoplásicos , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neovascularização Patológica , Neoplasias Ovarianas , Transdução de Sinais , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Animais , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Camundongos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Camundongos Nus , Células Endoteliais da Veia Umbilical Humana/metabolismo , Movimento Celular , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , AngiogêneseRESUMO
The p53 tumor suppressor is inactivated by mutations in about 50% of tumors. Rescuing the transcriptional function of mutant p53 has potential therapeutic benefits. Approximately 15% of p53 mutants are temperature sensitive (TS) and regain maximal activity at 32°C. Proof of concept study showed that induction of 32°C hypothermia in mice restored TS mutant p53 activity and inhibited tumor growth. However, 32°C is the lower limit of therapeutic hypothermia procedures for humans. Higher temperatures are preferable but result in suboptimal TS p53 activation. Recently, arsenic trioxide (ATO) was shown to rescue the conformation of p53 structural mutants by stabilizing the DNA binding domain. We examined the responses of 17 frequently observed p53 TS mutants to functional rescue by temperature shift and ATO. The results showed that ATO only rescued mild p53 TS mutants with high basal activity at 37°C. Mild TS mutants showed a common feature of regaining significant activity at the semi-permissive temperature of 35°C and could be further stimulated by ATO at 35°C. TS p53 rescue by ATO was antagonized by the cellular redox mechanism and was rapidly reversible. Inhibition of glutathione (GSH) biosynthesis enhanced ATO rescue efficiency and sustained p53 activity after ATO washout. The results suggest that mild TS p53 mutants are uniquely responsive to functional rescue by ATO due to small thermostability deficits and inherent potential to regain active conformation. Combining mild hypothermia and ATO may provide an effective and safe procedure for targeting tumors with p53 TS mutations.
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Trióxido de Arsênio , Arsenicais , Mutação , Óxidos , Proteína Supressora de Tumor p53 , Trióxido de Arsênio/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Arsenicais/farmacologia , Óxidos/farmacologia , Animais , Humanos , Camundongos , Hipotermia Induzida/métodos , Temperatura , Glutationa/metabolismoRESUMO
Rationale and objectives: To investigate the relationship between the pericoronary adipose tissue CT mean attenuation (PCATMA) measurement and image reconstruction parameters (adaptive statistical iterative reconstruction-veo (ASIR-V) percentage, kernel, and slice thickness). Materials and methods: One hundred and ninety-eight consecutive patients underwent CT coronary angiography at 100 kilovoltage peak (kVp) (n = 102) and 120 kVp (n = 96) were included. All scans were reconstructed by three means: 1. with 11 different ASIR-V percentages, standard kernel and 0.625 mm; 2. with soft, standard, detail, and bone kernels, 60 % ASIR-V, and 0.625 mm; 3. at 0.625 mm and 1.25 mm slice thickness, standard kernel and 60 % ASIR-V. PCATMA of the three main coronary arteries was calculated using a dedicated software. Linear regression, analysis of variance (ANOVA), Friedman test, and paired t-test were used for statistical analysis. Results: Linear regression of pooled average data showed that the PCATMA was positively and linearly correlated with the ASIR-V percentage (all R squared >0.99). Regression analysis of individual data showed that most R squared were greater than 0.8 or 0.9, but their slope consisted of a relatively wide range. The difference of PCATMA among different kernels for each coronary artery reached statistically significant levels (P < 0.001), particularly for the difference between standard and bone kernel. Most of the differences between 0.625 mm and 1.25 mm for LAD, LCX, and RCA at 100 kVp and 120 kVp reached statistical significance (P < 0.001). Conclusions: PCATMA correlates linearly with the strength of ASIR-V. Reconstruction kernel and slice thickness also affect PCATMA, especially for the sharp kernels.
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Chronic wounds impose a substantial economic burden on healthcare systems and result in decreased productivity. Honey possesses diverse properties, rendering it a promising, cost-effective, and efficacious intervention strategy for the management of chronic wounds. However, the findings are controversial. We have presented an updated and comprehensive systematic review and meta-analysis to evaluate the efficacy and safety of honey dressings in the management of chronic wounds. Nine electronic databases were systematically searched to identify relevant studies published prior to 22 March 2024. A total of eight studies, including 906 individuals that met the inclusion criteria, were incorporated. The findings demonstrated a significant acceleration in wound healing time with honey dressings (MD = -17.13, 95% CI -26.37 to -7.89, p = 0.0003) and an increase in the percentage of wound healing (MD = 18.31, 95% CI 8.86 to 27.76, p = 0.0001). No statistically significant differences were observed in the healing rate (RR = 2.00, 95% CI 0.78 to 5.10, p = 0.15), clearance time of bacteria (MD = -11.36, 95% CI: -25.91 to 3.18, p = 0.13) and hospital stay duration. Honey may decrease the VAS score but may increase the incidence of painful discomfort during treatment. The topical application of honey is an effective therapeutic approach for managing chronic wounds, but the quality of the evidence was very low due to the quality of risk of bias, inconsistency, and publication bias, highlighting the necessity for larger-scale studies with adequately powered RCTs to ensure the safety and efficacy of honey dressings in chronic wound healing.
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Bandagens , Mel , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Doença Crônica , Resultado do Tratamento , Ferimentos e Lesões/terapiaRESUMO
Objective: To investigate the risk factors associated with prolonged hospitalization in patients diagnosed with diabetic foot ulcers (DFU), to develop a predictive model, and to conduct internal validation of the model. Methods: The clinical data of DFU patients admitted to West China Hospital, Sichuan University between January 2012 and December 2022 were retrospectively collected. The subjects were randomly assigned to a training cohort and a validation cohort at a ratio of 7 to 3. Hospital stays longer than 75th percentile were defined as prolonged length-of-stay. A thorough analysis of the risk factors was conducted using the training cohort, which enabled the development of an accurate risk prediction model. To ensure robustness, the model was internally validated using the validation cohort. Results: A total of 967 inpatients with DFU were included, among whom 245 patients were identified as having an extended length-of-stay. The training cohort consisted of 622 patients, while the validation cohort comprised 291 patients. Multivariate logistic regression analysis revealed that smoking history (odds ratio [OR]=1.67, 95% confidence interval [CI], 1.13 to 2.48, P=0.010), Wagner grade 3 or higher (OR=7.13, 95% CI, 3.68 to 13.83, P<0.001), midfoot ulcers (OR=1.99, 95% CI, 1.07 to 3.72, P=0.030), posterior foot ulcers (OR=3.68, 95% CI, 1.83 to 7.41, P<0.001), multisite ulcers (OR=2.91, 95% CI, 1.80 to 4.69, P<0.001), wound size≥3 cm2 (OR=2.00, 95% CI, 1.28-3.11, P=0.002), and white blood cell count (OR=1.11, 95% CI, 1.05 to 1.18, P<0.001) were associated with an increased risk of prolonged length of stay. Additionally, a nomogram was constructed based on the identified risk factors. The areas under the receiver operating characteristic (ROC) curves for both the training cohort and the validation cohort were 0.782 (95% CI, 0.745 to 0.820) and 0.756 (95% CI, 0.694 to 0.818), respectively, indicating robust predictive performance. Furthermore, the calibration plot demonstrated optimal concordance between the predicted probabilities and the observed outcomes in both the training and the validation cohorts. Conclusion: Smoking history, Wagner grade≥3, midfoot ulcers, posterior foot ulcers, multisite ulcers, ulcer area≥3 cm2, and elevated white blood cell count are identified as independent predictors of prolonged hospitalization. Therefore, it is imperative that clinicians conduct a comprehensive patient evaluation and implement appropriate diagnostic and therapeutic strategies to effectively shorten the length of stay for DFU patients.
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Pé Diabético , Hospitalização , Tempo de Internação , Humanos , Estudos Retrospectivos , Fatores de Risco , Tempo de Internação/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , China/epidemiologia , Masculino , Feminino , Modelos Logísticos , Pessoa de Meia-Idade , Fumar/efeitos adversos , IdosoRESUMO
OBJECTIVES: To develop a prediction model based on spectral computed tomography (CT) to evaluate axillary lymph node (ALN) with macrometastases in clinical T1/2N0 invasive breast cancer. METHODS: A total of 217 clinical T1/2N0 invasive breast cancer patients who underwent spectral CT scans were retrospectively enrolled and categorized into a training cohort (n = 151) and validation cohort (n = 66). These patients were classified into ALN nonmacrometastases (stage pN0 or pN0 [i+] or pN1mi) and ALN macrometastases (stage pN1-3) subgroups. The morphologic criteria and quantitative spectral CT parameters of the most suspicious ALN were measured and compared. Least absolute shrinkage and selection operator (Lasso) was used to screen predictive indicators to build a logistic model. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the models. RESULTS: The combined arterial-venous phase spectral CT model yielded the best diagnostic performance in discrimination of ALN nonmacrometastases and ALN macrometastases with the highest AUC (0.963 in the training cohort and 0.945 in validation cohorts). Among single phase spectral CT models, the venous phase spectral CT model showed the best performance (AUC = 0.960 in the training cohort and 0.940 in validation cohorts). There was no significant difference in AUCs among the 3 models (DeLong test, P > .05 for each comparison). CONCLUSION: A Lasso-logistic model that combined morphologic features and quantitative spectral CT parameters based on contrast-enhanced spectral imaging potentially be used as a noninvasive tool for individual preoperative prediction of ALN status in clinical T1/2N0 invasive breast cancers.
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Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown. Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize. We show that their triple knockout mutants are nearly complete lack of stigmatic papilla, resulting in a severe reduction in kernel setting. Cellular examination reveals that stigmatic papilla is developed from a precursor cell, which is the smaller daughter cell resulting from asymmetric cell division of a silk epidermal cell. In situ hybridization shows that ZmSPL10, ZmSPL14 and their target genes SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A are preferentially expressed in the precursor cells of stigmatic papillae. Moreover, ZmSPL10, ZmSPL14 and ZmSPL26 directly bind to the promoters of SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A and promote their expression. Further, Zmwox3a knockout mutants display severe defects in stigmatic papilla formation and reduced seed setting. Collectively, our results demonstrate that ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla development through regulating auxin signaling and ZmWOX3A expression.
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Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Proteínas de Plantas , Transdução de Sinais , Zea mays , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação/genética , Flores/genética , Flores/crescimento & desenvolvimento , Regiões Promotoras Genéticas/genética , Genes de Plantas , Ligação Proteica , FenótipoRESUMO
Background: Several studies have shown that sodium-dependent glucose transporter 2 inhibitors can be used in the treatment of heart failure. This article summarized systematic reviews of sodium-dependent glucose transporter 2 inhibitors in the treatment of heart failure in order to evaluate efficacy and safety. Methods: We systematically searched eight electronic databases from inception to July 2023. We used Assessment of Multiple Systematic Reviews 2 to evaluate the methodological quality, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 to assess report quality, Risk of Bias in Systematic Review to assess the risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation to rate the quality of evidence. Outcome: A total of 36 systematic reviews were included. Our results were classified as clear evidence of benefit: hospitalization for heart failure; possible benefit: cardiovascular death (mortality) and renal outcome composite; clear evidence of no effect or equivalence: atrial arrhythmias, ventricular arrhythmia, atrial fibrillation, and hypotension; possible harm: genital infection; insufficient evidence to draw a conclusion: atrial flutter, major adverse cardiovascular events, urinary tract infection, acute kidney injury, hypoglycemia, and bone fracture. Conclusions: Sodium-dependent glucose transporter 2 inhibitors are beneficial for the treatment of heart failure, especially in terms of heart failure hospitalization.
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Since the patients suffering from female lower genital tract diseases are getting younger and younger and the human papilloma virus (HPV) infection is becoming more widespread, the novel non-invasive precise modalities of diagnosis and therapy are required to remain structures of the organ and tissue, and fertility as well, by which the less damage to normal tissue and fewer adverse effects are able to be achieved. In all nucleated mammalian cells, 5-Aminolevulinic acid (5-ALA) is an amino acid that occurs spontaneously, which further synthesizes in the heme biosynthetic pathway into protoporphyrin IX (PpIX) as a porphyrin precursor and photosensitizing agent. Exogenous 5-ALA avoids the rate-limiting step in the process, causing PpIX buildup in tumor tissues. This tumor-selective PpIX distribution after 5-ALA application has been used successfully for tumor photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Several ALA-based drugs have been used for ALA-PDD and ALA-PDT in treating many (pre)cancerous diseases, including the female lower genital tract diseases, yet the ALA-induced fluorescent theranostics is needed to be explored further. In this paper, we are going to review the studies of the mechanisms and applications mainly on ALA-mediated photodynamic reactions and its effectiveness in treating female lower genital tract diseases.