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1.
Int J Surg ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954672

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

2.
J Microbiol Biotechnol ; 34(7): 1544-1549, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38956864

RESUMO

This study presents a fluorescent mechanism for two-step amplification by combining two widely used techniques, exponential amplification reaction (EXPAR) and catalytic hairpin assembly (CHA). Pseudomonas aeruginosa (P. aeruginosa) engaged in competition with the complementary DNA in order to attach to the aptamer that had been fixed on the magnetic beads. The unbound complementary strand in the liquid above was utilized as a trigger sequence to initiate the protective-EXPAR (p-EXPAR) process, resulting in the generation of a substantial quantity of short single-stranded DNA (ssDNA). The amplified ssDNA can initiate the second CHA amplification process, resulting in the generation of many double-stranded DNA (dsDNA) products. The CHA reaction was initiated by the target/trigger DNA, resulting in the release of G-quadruplex sequences. These sequences have the ability to bond with the fluorescent amyloid dye thioflavin T (ThT), generating fluorescence signals. The method employed in this study demonstrated a detection limit of 16 cfu/mL and exhibited a strong linear correlation within the concentration range of 50 cfu/mL to 105 cfu/mL. This method of signal amplification has been effectively utilized to create a fluorescent sensing platform without the need for labels, enabling the detection of P. aeruginosa with high sensitivity.

3.
J Cancer ; 15(13): 4219-4231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947379

RESUMO

Background: Hepatocellular carcinoma (HCC), the predominant malignancy of the digestive tract, ranks as the third most common cause of cancer-related mortality globally, significantly impeding human health and lifespan. Emerging immunotherapeutic approaches have ignited fresh optimism for patient outcomes. This investigation probes the link between 731 immune cell phenotypes and HCC through Mendelian Randomization and single-cell sequencing, aiming to unearth viable drug targets and dissect HCC's etiology. Methods: We conducted an exhaustive two-sample Mendelian Randomization analysis to ascertain the causal links between immune cell features and HCC, utilizing publicly accessible genetic datasets to explore the causal connections of 731 immune cell traits with HCC susceptibility. The integrity, diversity, and potential horizontal pleiotropy of these findings were rigorously assessed through extensive sensitivity analyses. Furthermore, single-cell sequencing was employed to penetrate the pathogenic underpinnings of HCC. Results: Establishing a significance threshold of pval_Inverse.variance.weighted at 0.05, our study pinpointed five immune characteristics potentially elevating HCC risk: B cell % CD3- lymphocyte (TBNK panel), CD25 on IgD+ (B cell panel), HVEM on TD CD4+ (Maturation stages of T cell panel), CD14 on CD14+ CD16- monocyte (Monocyte panel), CD4 on CD39+ activated Treg ( Treg panel). Conversely, various cellular phenotypes tied to BAFF-R expression emerged as protective elements. Single-cell sequencing unveiled profound immune cell phenotype interactions, highlighting marked disparities in cell communication and metabolic activities. Conclusion: Leveraging MR and scRNA-seq techniques, our study elucidates potential associations between 731 immune cell phenotypes and HCC, offering a window into the molecular interplays among cellular phenotypes, and addressing the limitations of mono-antibody therapeutic targets.

4.
J Transl Med ; 22(1): 606, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951801

RESUMO

BACKGROUND: The spatial context of tumor-infiltrating immune cells (TIICs) is important in predicting colorectal cancer (CRC) patients' clinical outcomes. However, the prognostic value of the TIIC spatial distribution is unknown. Thus, we aimed to investigate the association between TIICs in situ and patient prognosis in a large CRC sample. METHODS: We implemented multiplex immunohistochemistry staining technology in 190 CRC samples to quantify 14 TIIC subgroups in situ. To delineate the spatial relationship of TIICs to tumor cells, tissue slides were segmented into tumor cell and microenvironment compartments based on image recognition technology, and the distance between immune and tumor cells was calculated by implementing the computational pipeline phenoptr. RESULTS: MPO+ neutrophils and CD68+IDO1+ tumor-associated macrophages (TAMs) were enriched in the epithelial compartment, and myeloid lineage cells were located nearest to tumor cells. Except for CD68+CD163+ TAMs, other cells were all positively associated with favorable prognosis. The prognostic predictive power of TIICs was highly related to their distance to tumor cells. Unsupervised clustering analysis divided colorectal cancer into three subtypes with distinct prognostic outcomes, and correlation analysis revealed the synergy among B cells, CD68+IDO1+TAMs, and T lineage cells in producing an effective immune response. CONCLUSIONS: Our study suggests that the integration of spatial localization with TIIC abundance is important for comprehensive prognostic assessment.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Microambiente Tumoral/imunologia , Análise por Conglomerados , Idoso , Linfócitos do Interstício Tumoral/imunologia , Imuno-Histoquímica , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Análise Espacial
5.
Transfus Apher Sci ; 63(4): 103964, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38959809

RESUMO

BACKGROUND: Platelet plays a vital role in both physiological and pathological processes. However, the limited storage time of platelet in vitro poses an immense challenge for its applications because of the increased risk of bacterial contamination and platelet storage lesions. Agitation can inhibit lesions by facilitating continuous oxygenation of platelets and permitting excess carbon dioxide to be removed during storage. However, it is still not known whether agitating BCs gives a positive effect on platelet quality. OBJECTIVES: To evaluate the quality difference between platelet concentrates (PCs) from buffy coats (BCs) held rest and agitation. METHODS: Samples were withdrawn for cell count, blood gas analysis, free hemoglobin level, hypotonic shock response, maximum aggregation rate, activation marker expression (CD62P and CD42b) and coagulation function. RESULTS: We found the PCs prepared from the agitating BCs had fewer residual WBCs, exhibited a better gas exchange ability, slower metabolism (higher pH, higher content glucose, and lower lactic acid levels), better hypotonic shock response, and lower levels of CD62P. The TEG-PC assays showed no difference in coagulation function. CONCLUSION: Our findings showed that BC can be agitated overnight before a soft spin.

6.
Clin Exp Hypertens ; 46(1): 2373467, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38963020

RESUMO

BACKGROUND: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. METHODS: db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. RESULTS: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. CONCLUSIONS: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.


Assuntos
Diferenciação Celular , Diabetes Mellitus Experimental , Interleucina-17 , Condicionamento Físico Animal , Fator de Transcrição STAT3 , Células Th17 , Vasodilatação , Animais , Camundongos , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Vasodilatação/fisiologia , Fator de Transcrição STAT3/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/terapia , Masculino , Interleucina-17/sangue , Interleucina-17/metabolismo , Endotélio Vascular/fisiopatologia , Resistência à Insulina/fisiologia , Transdução de Sinais , Camundongos Endogâmicos C57BL , Aorta/fisiopatologia
7.
Orphanet J Rare Dis ; 19(1): 247, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38956624

RESUMO

BACKGROUND: The safety and efficacy of vaccination against coronavirus disease 2019 (COVID-19) in patients with lymphangioleiomyomatosis (LAM) is still unclear. This study investigates COVID-19 vaccine hesitancy, vaccine safety and efficacy, and COVID-19 symptoms in LAM patients. RESULTS: In total, 181 LAM patients and 143 healthy individuals responded to the questionnaire. The vaccination rate of LAM patients was 77.34%, and 15.7% of vaccinated LAM patients experienced adverse events. Vaccination decreased the risk of LAM patients developing anorexia [OR: 0.17, 95% CI: (0.07, 0.43)], myalgia [OR: 0.34, 95% CI: (0.13, 0.84)], and ageusia [OR: 0.34, 95% CI: (0.14, 0.84)]. In LAM patients, a use of mTOR inhibitors reduced the risk of developing symptoms during COVID-19, including fatigue [OR: 0.18, 95% CI: (0.03, 0.95)], anorexia [OR: 0.30, 95% CI: (0.09, 0.96)], and ageusia [OR: 0.20, 95% CI: (0.06, 0.67)]. CONCLUSIONS: Vaccination rates in the LAM population were lower than those in the general population, as 22.7% (41/181) of LAM patients had hesitations regarding the COVID-19 vaccine. However, the safety of COVID-19 vaccination in the LAM cohort was comparable to the healthy population, and COVID-19 vaccination decreased the incidence of COVID-19 symptoms in LAM patients. In addition, mTOR inhibitors seem not to determine a greater risk of complications in patients with LAM during COVID-19.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Linfangioleiomiomatose , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Feminino , Estudos Retrospectivos , Adulto , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Pessoa de Meia-Idade , Masculino , SARS-CoV-2 , Vacinação , China/epidemiologia , População do Leste Asiático
8.
Front Pharmacol ; 15: 1349105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962301

RESUMO

Emergence delirium is a common postoperative complication in patients undergoing general anesthesia, especially in children. In severe cases, it can cause unnecessary self-harm, affect postoperative recovery, lead to parental dissatisfaction, and increase medical costs. With the widespread use of inhalation anesthetic drugs (such as sevoflurane and desflurane), the incidence of emergence delirium in children is gradually increasing; however, its pathogenesis in children is complex and unclear. Several studies have shown that age, pain, and anesthetic drugs are strongly associated with the occurrence of emergence delirium. Alterations in central neurophysiology are essential intermediate processes in the development of emergence delirium. Compared to adults, the pediatric nervous system is not fully developed; therefore, the pediatric electroencephalogram may vary slightly by age. Moreover, pain and anesthetic drugs can cause changes in the excitability of the central nervous system, resulting in electroencephalographic changes. In this paper, we review the pathogenesis of and prevention strategies for emergence delirium in children from the perspective of brain electrophysiology-especially for commonly used pharmacological treatments-to provide the basis for understanding the development of emergence delirium as well as its prevention and treatment, and to suggest future research direction.

9.
Phytomedicine ; 132: 155848, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38964157

RESUMO

BACKGROUND: Borneol, a highly lipid-soluble bicyclic terpene mainly extracted from plants, is representative of monoterpenoids. Modern medicine has established that borneol exhibits a range of pharmacological activities and used in the treatment of many diseases, particularly Cardio-cerebrovascular diseases (CVDs). The crucial role in enhancing drug delivery and improving bioavailability has attracted much attention. In addition, borneol is also widely utilized in food, daily chemicals, fragrances, and flavors industries. PURPOSE: This review systematically summarized the sources, pharmacological activities and mechanisms, clinical trial, pharmacokinetics, toxicity, and application of borneol. In addition, this review describes the pharmacological effects of borneol ester and the combination of borneol with nanomaterial. This review will provide a valuable resource for those pursuing researches on borneol inspiring the pharmacological applications in the medicine, food and daily chemical products, and developing of new drugs containing borneol or its derivatives. METHODS: This review searched the keywords ("borneol" or "bornyl esters") and ("pharmacology" or "Traditional Chinese medicine" or "Cardio-cerebrovascular diseases" or "blood-brain barrier" or "ischemic stroke" or "nanomaterials" or "neurodegenerative diseases" or "diabetes" or "toxicity") in Web of Science, PubMed, Google Scholar and China National Knowledge Infrastructure (CNKI) from January 1990 to May 2024. The search was limited to articles published in English and Chinese. RESULTS: Borneol exhibits extensive pharmacological activities including anti-inflammatory effects, analgesia, antioxidation, and has the property of crossing biological barriers and treating CVDs. The intrinsic molecular mechanisms are involved in multiple components, such as regulation of various key factors (including Tumor necrosis factor-α, Nuclear factor kappa-B, Interleukin-1ß, Malondialdehyde), inhibiting transporter protein function, regulating biochemical levels, and altering physical structural changes. In addition, this review describes the pharmacological effects of borneol ester and the combination of borneol with nanomaterial. CONCLUSION: The pharmacological properties and applications of borneol are promising, including anti-inflammatory, analgesic, antimicrobial, and antioxidant properties, as well as enhancing drug delivery and treating CVDs. However, its clinical application is hindered by the limited research on safety, efficacy, and pharmacokinetics. Therefore, this review systemically summarized the advances on pharmacological activities and mechanisms of the borneol. Standardized clinical trials and exploration of synergistic effects with other drugs were also are outlined.

10.
Front Pharmacol ; 15: 1433540, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966543

RESUMO

This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease's epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients.

11.
J Med Chem ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968440

RESUMO

Herein, a series of novel arylpiperazine (piperidine) derivatives were designed, synthesized, and evaluated for mechanisms of action through in vitro and in vivo studies. The most promising compound, II-13 (later named as MT-1207), is a potent α1 and 5-HT2A receptor antagonist with remarkable IC50 in the picomolar level. Importantly, in the in vivo assay, II-13 achieved an effective blood pressure (BP) reduction in the 2K2C rat model without damaging renal function. Compound II-13, with its significant advantages in terms of pharmacological effects, pharmacokinetic parameters, and a large safety window, was extensively investigated. Moreover, data also showed that compound II-13 had fewer side effects in a postural BP assay and could prevent the onset of postural hypotension. Together, these results suggested that compound II-13 is a highly potent antihypertensive drug candidate with multitarget mechanisms of action in preclinical models. Currently, MT-1207 is in phase II hypertensive clinical trials in China.

12.
Eur J Surg Oncol ; 50(9): 108516, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38968853

RESUMO

OBJECTIVE: To investigate the association between household income and overall survival (OS) of patients with cervical adenocarcinoma. METHODS: We conducted a retrospective cohort study involving participants selected from the Surveillance, Epidemiology, and End Results (SEER) database. Data were collected on various variables, including demographic variables such as median household income and clinicopathological characteristics for all participants. Cox regression analysis was utilized to examine the association between household income and OS. Subgroup analysis, sensitivity analysis, and E-value were used to further confirm the association. RESULTS: A total of 2217 patients were included in the study. Compared with low-income (<$35,000-$54,999), middle-income (55,000-$69,999) or high-income (≥$70,000) was significantly associated with a higher 5-year OS (70.8 %, 58.7 % vs 50 %) in patients with cervical adenocarcinoma. The HR was 0.49, 95 % CI 0.41-0.58, p < 0.001 and 0.66 (0.55-0.78), p < 0.001 respectively, in the unadjusted model. After adjustment for potential confounders, the results were similar (adjusted HR 0.54 (0.45-0.65), p < 0.001) and 0.79 (0.66-0.94), p = 0.01), respectively. This significant association was also present in the various adjusted models. Subgroup and sensitivity analyses suggested that the relationship remained robust and reliable. The E-value analysis indicated robustness to unmeasured confounding. There was evidence of an interaction between age at diagnosis, race, primary site, tumor grade, T, N, M, or Scope Reg LN Sur, and household income on increasing the 5-year OS of cervical adenocarcinoma. CONCLUSIONS: Our study found that middle or high household income was significantly associated with a better 5-year OS compared with low household income in patients with cervical adenocarcinoma.

13.
Sci Rep ; 14(1): 15400, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965329

RESUMO

The clinical incidence of sjogren's syndrome combined with gastroesophageal reflux disease is high. Existing observational studies have shown inconsistent results in the association between gastroesophageal reflux disease (GERD) and Sjogren's syndrome (SS).We observed that the symptoms of SS patients also improved after receiving GERD-related treatment. Therefore, we aimed to investigate the relationship between GERD and SS through a bidirectional two-sample Mendelian randomization (MR) study. Independent SNPs associated with GERD and SS were selected from a genome-wide association study (GWAS) as instrumental variables to conduct a bidirectional two-sample Mendelian analysis of GERD and SS. Genetic data were obtained from two databases for the following two outcomes: Gastroesophageal reflux (IEU Open GWAS) [sample size = 602,604 (patients = 129,080; nonpatients = 473,524)] and SS (FinnGen) [sample size = 392,423 (patients = 2,495; nonpatients = 389,928)]. Statistical methods for the MR analysis included the inverse-variance weighting method, weighted median, simple mode and weighted mode, as well as heterogeneity and sensitivity analyses using the Cochran Q statistic, MR‒Egger regression, outlier detection methods (MR-PRESSO). In addition, Steiger Test was conducted to test the direction of causality. MR analysis showed a positive correlation between GERD and SS risk [odds ratio (OR) = 1.3279 (95% confidence interval 1.0312-1.7099, P = 0.0280)]. However, in contrast, no significant causal effect of SS on GERD was observed [OR = 1.0024 (95% CI 0.9651-1.0412; P = 0.8995)]. This bidirectional two-sample Mendelian randomization study confirmed a causal relationship between SS and GERD, and suggested that GERD is a risk factor for SS, while SS does not affect GERD.


Assuntos
Refluxo Gastroesofágico , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren , Humanos , Refluxo Gastroesofágico/genética , Síndrome de Sjogren/genética , Síndrome de Sjogren/complicações , Predisposição Genética para Doença , Feminino
14.
J Environ Manage ; 366: 121675, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971068

RESUMO

This study provides first evidence on the effects of Chinese FDI (Foreign Direct Investment) outflows on host country environments. The study draws upon a comprehensive dataset covering aggregate Chinese FDI outflows and sector specific data into 65 host nations over the 2007-2019 period. Employing a STIRPAT (Stochastic Regression on Population, Affluence and Technology) model and several different techniques including DID (Difference-in-Difference), pooled OLS (Ordinary Least Squares), quantile regression, IV (Instrumental Variable) estimation, threshold and Tobit regression, the findings suggest that Chinese FDI leads to an increase in host country CO2 (Carbon Dioxide) emissions, aligning with the pollution haven hypothesis at the aggregate level. A closer investigation at the development regime and sectoral levels indicates that in the low development regime, FDI inflows into the financial and real estate sector increase emissions. Conversely in the high-income regime, Chinese FDI into the entertainment sector is associated with an increase in carbon emissions. Chinese FDI is further found to lead to an increase in emissions in countries with a per capita GDP (Gross Domestic Product) of below USD72041.7. However, as per capita income rises above USD72041.7, FDI leads to a fall in carbon emissions.

15.
Int Immunopharmacol ; 138: 112463, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971110

RESUMO

Intestinal ischemia/reperfusion injury (IRI) poses a serious threat to human survival and quality of life with high mortality and morbidity rates. The current absence of effective treatments for intestinal IRI highlights the urgent need to identify new therapeutic targets. Ursolic acid (UA), a pentacyclic triterpene natural compound, has been shown to possess various pharmacological properties including intestinal protection. However, its potential protective efficacy on intestinal IRI remains elusive. This study aimed to investigate the effect of UA on intestinal IRI and explore the underlying mechanisms. To achieve this, we utilized network pharmacology to analyze the mechanism of UA in intestinal IRI and assessed UA's effects on intestinal IRI using a mouse model of superior mesenteric artery occlusion/reperfusion and an in vitro model of oxygen-glucose deprivation and reperfusion-induced IEC-6 cells. Our results demonstrated that UA improved necroptosis through the RIP1/RIP3/MLKL pathway, reduced necroinflammation via the HMGB1/TLR4/NF-κB pathway, attenuated morphological damage, and enhanced intestinal barrier function. Furthermore, UA pretreatment downregulated the phosphorylation level of signal transducer and activator of transcription 3 (STAT3). The effects of UA were attenuated by the STAT3 agonist Colivelin. In conclusion, our study suggests that UA can improve intestinal IRI by inhibiting necroptosis in enterocytes via the suppression of STAT3 activation. These results provide a theoretical basis for UA treatment of intestinal IRI and related clinical diseases.

16.
Front Oncol ; 14: 1418417, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978732

RESUMO

Background: Imatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system. Methods: We retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores. Results: The area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778-0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P<0.05). Conclusion: We constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.

18.
Front Med (Lausanne) ; 11: 1415545, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988359

RESUMO

Acquired reactive perforating collagenosis (ARPC) is a rare dermatological disorder condition defined by the perforation of altered collagen fibers through the epidermis. The presence of underlying conditions such as diabetes or renal disease is helpful in the ARPC diagnosis. Although skin rashes related to ARPC have been reported, the exact causative factors and mechanisms remain unclear. Here, we present a unique case of ARPC triggered by trauma in a 67-year-old male without concurrent systemic alterations. The diagnosis of ARPC with eosinophilia was made following comprehensive diagnostic testing, including clinical presentation, histological results, and blood tests, ruling out other possible diseases. Intriguingly, the histopathological examination revealed collagen penetration into the epidermis at different tissue sections. In addition, we reviewed existing literature on ARPC, which documented the causation. To help confirm the diagnosis, clinicians have to pay attention to traumatic triggers for ARPC and its rare manifestation with eosinophilia.

20.
Heliyon ; 10(12): e32781, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975116

RESUMO

Background: Type 1 diabetes mellitus (T1DM) may be associated with various autoimmune diseases, but the causal relationship between T1DM and autoimmune skin diseases is not yet clear. Methods: The summary statistical data on T1DM and nine autoimmune skin diseases in European populations were extracted for mendelian randomization (MR) analysis. Subsequently, the analysis was replicated in East Asian populations. In the MR estimation, inverse variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were utilized. Outliers were excluded using MR-PRESSO, and horizontal pleiotropy was assessed with MR-Egger. Additionally, a multivariable MR analysis was conducted to investigate whether T1DM has an independent effect on autoimmune skin diseases after adjusting for potential confounders. Results: In Europe, the MR estimated based on IVW method indicated a causal association between genetically determined T1DM and systemic lupus erythematosus (SLE) (OR = 1.38, 95%CI: 1.26-1.50, p<0.01), rheumatoid arthritis (RA) (OR = 1.15, 95%CI: 1.05-1.25, p<0.01), as well as multiple sclerosis (MS) (OR = 1.17, 95%CI: 1.01-1.36, p = 0.04), but there is no association between T1DM and atopic dermatitis (AD), vitiligo, lichen planus (LP), hidradenitis suppurativa (HS), alopecia areata (AA) and systemic sclerosis (SS). After adjusting for time spent watching television, body mass index, type 2 diabetes mellitus, and body fat percentage, we found a causal relationship between T1DM and SLE (OR = 1.29, 95%CI: 1.16-1.44, p < 0.01), RA (OR = 1.28, 95%CI: 1.20-1.38 p < 0.01) and MS (OR = 1.11, 95%CI: 1.04-1.18, p < 0.01). Then, no genetic causal association was found between TIDM and SLE, and AD in East Asia. These results didn't exhibit horizontal pleiotropy, and "leave-one-out" analysis demonstrated result stability. Conclusion: Our MR research indicates a causal relationship between T1DM and SLE, RA, and MS in Europe. However, no causal relationship between T1DM and SLE has been observed in East Asia. Therefore, it is important to regularly monitor relevant immunological markers of SLE, RA, and MS in T1DM patients and take preventive measures.

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