RESUMO

BACKGROUND: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. OBJECTIVE: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. METHODS: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. RESULTS: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. CONCLUSION: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Assuntos

Doenças Cardiovasculares , Glicopeptídeos , Falência Renal Crônica , Diálise Renal , Humanos , Glicopeptídeos/sangue , Diálise Renal/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Idoso , Biomarcadores/sangue

RESUMO

Thrombosis, a prevalent condition, can provoke severe health issues like acute coronary syndrome (ACS), deep vein thrombosis (DVT), and pulmonary embolism (PE). The rising incidence of these diseases annually significantly impacts patient wellbeing and poses a substantial burden on healthcare systems. Recombinant neorudin is a developing anticoagulant drug for thrombotic diseases whose phase I clinical trials has been completed. The distribution pattern of it and its active metabolite, hirudin, in thrombi, blood surrounding the thrombus and peripheral blood remains uncertain. This study explored their distribution using a rat arteriovenous bypass thrombosis model, revealing higher neorudin levels in blood surrounding the thrombus and elevated hirudin concentrations in thrombus. Recombinant neorudin significantly increased Thrombin Time (TT) in both plasma surrounding the thrombus and peripheral blood, and reduced the wet weight of the thrombus. The results above demonstrated the anticoagulant and antithrombotic efficacy of recombinant neorudin in vivo. Give the distribution pattern of neorudin and hirudin, we hypothesized that neorudin was cleaved at the site of thrombus formation to produce hirudin, leading to the rapid accumulation of hirudin within local thrombi and resulting in a higher concentration inside the thrombus. This insight was crucial for understanding the action mechanisms of anticoagulants in thrombosis management and provided a valuable guidance for therapeutic strategies in treating thrombotic diseases.

RESUMO

Bioelectronic implants featuring soft mechanics, excellent biocompatibility, and outstanding electrical performance hold promising potential to revolutionize implantable technology. These biomedical implants can record electrophysiological signals and execute direct therapeutic interventions within internal organs, offering transformative potential in the diagnosis, monitoring, and treatment of various pathological conditions. However, challenges remain in improving excessive impedance at the bioelectronic-tissue interface and thus the efficacy of electrophysiological signaling and intervention. Here, we devise orbit symmetry breaking in MXene (a low-cost scalability, biocompatible, and conductive two dimensionally layered material, which we refer to as OBXene), which exhibits low bioelectronic-tissue impedance, originating from the out-of-plane charge transfer. Furthermore, the Schottky-induced piezoelectricity stemming from the asymmetric orbital configuration of OBXene facilitates interlayered charge transport in the device. We report an OBXene-based cardiac patch applied on the left ventricular epicardium of both rodent and porcine models to enable spatiotemporal epicardium mapping and pacing while coupling the wireless and battery-free operation for long-term real-time recording and closed-loop stimulation.

Assuntos

Próteses e Implantes , Animais , Suínos , Órbita/cirurgia , Impedância Elétrica , Materiais Biocompatíveis/química

RESUMO

With the in-depth knowledge of the pathological and physiological characteristics of the intestinal barrier-portal vein/intestinal lymphatic vessels-systemic circulation axis, oral targeted drug delivery is frequently being renewed. With many advantages, such as high safety, convenient administration, and good patient compliance, many researchers have begun to explore targeted drug delivery from intravenous injections to oral administration. Over the past few decades, the fields of materials science and nanomedicine have produced various drug delivery platforms that hold great potential in overcoming the multiple barriers associated with oral drug delivery. However, the oral transport of particles into the systemic circulation is extremely difficult due to immune rejection and biochemical invasion in the intestine, which limits absorption and entry into the bloodstream. The feasibility of the oral delivery of targeted drugs to sites outside the gastrointestinal tract (GIT) is unknown. This article reviews the biological barriers to drug absorption, the in vivo fate and transport mechanisms of drug carriers, the theoretical basis for oral administration, and the impact of carrier structural evolution on oral administration to achieve this goal. Finally, this article reviews the characteristics of different nano-delivery systems that can enhance the bioavailability of oral therapeutics and highlights their applications in the efficient creation of oral anticancer nanomedicines.

Assuntos

Antineoplásicos , Nanomedicina , Neoplasias , Humanos , Nanomedicina/métodos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/química , Administração Oral , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Disponibilidade Biológica , Nanopartículas/química , Nanopartículas/administração & dosagem

RESUMO

This retrospective study demonstrated that patients with advanced non-small cell lung cancer who experienced any-grade or grade 1-2 immune-related adverse events (irAEs) with immune checkpoint inhibitor plus chemotherapy (ICI+Chemo) as first-line treatment regimen had significantly longer progression-free survival (PFS; p < 0.001) and overall survival (OS; p < 0.05) compared with patients without any irAE. Three variables were identified as predictors of favorable PFS and OS: absence of baseline brain metastasis (p < 0.05), receiving first-line ICI+Chemo (p < 0.01), and occurrence of any grade adverse events (p < 0.001). Using these three variables, two nomograms were generated to predict PFS and OS, which were validated using two independent cohorts treated with Chemo or ICI+Chemo (n = 161) or ICI monotherapy (n = 109). Patients with low scores in discovery and validation cohorts consistently had significantly longer PFS (p < 0.001) and OS (p < 0.05) than those with high scores. Our findings provide preliminary evidence of the clinical utility of a nomogram in prognosticating ICI-treated patients.

RESUMO

In order to understand the status of aflatoxin contamination in dried chilli products in Gansu Province and the risk of dietary exposure, a total of 106 samples of dried chilli products from farmers' markets and supermarkets in 14 prefecture-cities of Gansu Province were collected and analysed by isotope dilution liquid chromatography-tandem mass spectrometry. The results showed that the detection rate of aflatoxin in dried chilli products in Gansu Province was 30.2%, and the average level was 1.57 µg/kg. The detection rates of dried chillies, paprika, and chilli powders were 16.7%, 43.6%, and 46.2%, respectively. The detection rates of aflatoxin in dried chilli products from shops and farmers' markets were 22.5% and 40.0%, respectively. The dietary exposure of AFB1 was 0.0001 µg/kg bw/day, and the MOE calculated from its average concentration was 305.

RESUMO

Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

Assuntos

COVID-19 , Miastenia Gravis , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Fatores de Risco , Idoso , Índice de Gravidade de Doença , Comorbidade

RESUMO

Coastal areas are regions of active interaction between the sea and land and are highly sensitive to changes in heavy metal contamination caused by natural and anthropogenic activities. The contents of heavy metals in 80 surface sediments in the Qizhou Island sea area in the northeast of Hainan Island were determined to assess the contamination status, spatial distribution, sources, and ecological risks. The results indicate that the main factors influencing the distribution patterns and contents of heavy metals are hydrodynamic conditions and sources of materials. The accumulation of Cd and Pb in the sediments is attributed to the combined effects of natural sources and anthropogenic input. In addition to widespread anthropogenic influence, the enrichment of Cd in the southeastern outer shelf area of the study region may be controlled by biogenic carbonate rocks or enhanced input of near-source materials during the late Pleistocene low sea level period.

RESUMO

BACKGROUND: It is uncertain whether the weekend warrior pattern is associated with all-cause mortality among adults living with type 2 diabetes. This study explored how the 'weekend warrior' physical activity (PA) pattern was associated with all-cause mortality among adults living with type 2 diabetes. METHODS: This prospective cohort study investigated US adults living with type 2 diabetes in the National Health and Nutrition Examination Survey (NHANES). Mortality data was linked to the National Death Index. Based on self-reported leisure-time and occupational moderate-to-vigorous PA (MVPA), participants were categorized into 3 groups: physically inactive (< 150 min/week of MVPA), weekend warrior (≥ 150 min/week of MVPA in 1 or 2 sessions), and physically active (≥ 150 min/week of MVPA in 3 or more sessions). RESULTS: A total of 6067 participants living with type 2 diabetes [mean (SD) age, 61.4 (13.5) years; 48.0% females] were followed for a median of 6.1 years, during which 1206 deaths were recorded. Of leisure-time and occupational activity, compared with inactive individuals, hazard ratios (HRs) for all-cause mortality were 0.49 (95% CI 0.26-0.91) and 0.57 (95% CI 0.38-0.85) for weekend warrior individuals, and 0.55 (95% CI 0.45-0.67) and 0.64 (95% CI 0.53-0.76) for regularly active individuals, respectively. However, when compared leisure-time and occupational weekend warrior with regularly active participants, the HRs were 0.82 (95% CI 0.42-1.61) and 1.00 (95% CI 0.64-1.56) for all-cause mortality, respectively. CONCLUSIONS: Weekend warrior PA pattern may have similar effects on lowering all-cause mortality as regularly active pattern among adults living with type 2 diabetes, regardless of leisure-time or occupational activity. Therefore, weekend warrior PA pattern may be sufficient to reduce all-cause mortality for adults living with type 2 diabetes.

RESUMO

This study aimed to evaluate the safety and efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) and stenting for treating acute iliofemoral deep venous thrombosis (DVT) combined with iliac vein compression syndrome (IVCS), and to identify the predictors of stent restenosis. Patients with acute proximal DVT combined with IVCS underwent PCDT and stenting from January 2017 to December 2022 were enrolled. Primary and secondary patency were assessed by duplex ultrasound (DUS). The morbidity of postthrombotic syndrome (PTS) was assessed by the Villalta score. Risk factors for stent restenosis were assessed using univariate and multivariate Cox regression models. Total of 254 patients were included. The mean follow-up time was 36.06 ± 17.66 months. The primary patency rates at 1 year, 3 years, and 5 years were 92.5%±1.7%, 85.4%±2.4%, and 82.4%±2.9%, respectively. The incidence of stent restenosis was 14.2%. Discontinuation of anticoagulants within one year [hazard ratio (HR) = 5.03; P = .048] was the factor associated with acute in-stent thrombosis. Previous DVT history (HR =2.29; P = .037) and stent placement across the inguinal ligament (HR =6.70; P < .001) were identified as independent risk factors significantly associated with stent restenosis. The overall PTS rate was 19.3%. PCDT with stenting is safe and effective for patients with iliofemoral DVT secondary to IVCS, leading to low rates of PTS. Previous DVT history and stents placed across the inguinal ligament may be predictors of stent restenosis. Furthermore, stent restenosis typically occurs within one year and is mainly caused by acute thrombosis due to discontinuation of anticoagulants.

Assuntos

Veia Ilíaca , Stents , Trombose Venosa , Humanos , Masculino , Feminino , Trombose Venosa/etiologia , Stents/efeitos adversos , Fatores de Risco , Pessoa de Meia-Idade , Síndrome de May-Thurner/complicações , Síndrome de May-Thurner/terapia , Adulto , Resultado do Tratamento , Idoso , Síndrome Pós-Trombótica/etiologia

RESUMO

Elucidating exposure risks associated with the most widely used agrochemicals and their metabolites in celery agrosystems are vital for food safety and human health. The occurrence, distribution, dissipation and metabolism of imidacloprid (IMI), acetamiprid (ACE), thiamethoxam (THM) and difenoconazole (DIF) in celery tissues reflected by initial depositions, uptake characteristics, half-lives, concentration variations. DIF exhibited unacceptable ecological risk to soil organisms under multi-risk evaluation models, including toxicity exposure ratio, risk quotient, and BITSSD model. The joint dietary risks of target pesticides were 37.273-647.454% and 0.400-2522.016% based on deterministic and probabilistic models, with non-carcinogenic risks of 30.207-85.522% and 1.229-2524.662%, respectively. Children aged 1-6 years suffered the highest exposure, with the leaves posing higher risk than other tissues. Long-term exposure risks should be continuously assessed for ecological sustainability and human health, given the widespread usage and cumulative effects of target pesticides, especially for rural children.

RESUMO

BACKGROUND: Inadequate postoperative analgesia greatly affects the recovery of patients, can poses a substantial health and economic burden. Patient-controlled analgesia is the most commonly used method for postoperative pain relief. However, the situation of inadequate analgesia still exists. Artificial intelligent Patient-controlled analgesia (Ai-PCA) system can make it easier for medical staff to understand the pain level of patients in order to deal with it in time. So far, several studies have investigated anesthesiologists' knowledge and management of Ai-PCA. OBJECTIVE: This study aimed to assess the degree of anesthesiologists' knowledge, attitude and their practice (KAP) towards Ai-PCA in east China's Jiangsu Province. METHODS: This cross-sectional study was conducted among 396 anesthesiologists working in tertiary hospitals. The data were collected using a pretested, structured and self-administered KAP questionnaire. The data were analyzed using Independent t-test, analysis of variance, Pearson's correlation and multiple linear regression tests. RESULTS: Five hundred twelve questionnaires were collected, 396 anesthesiologists (190 Male, and 206 Female) were included in our study for statistical analysis. The score of knowledge, attitude, practice was 5.49 ((SD = 1.65; range:0-8), 37.45 (SD = 4.46; range:9-45), and 26.41 (SD = 9.61; range:9-45), respectively. Among the participants, 309 (78%) and 264 (66.7%) had good knowledge and positive attitudes toward Ai-PCA, respectively. However, only 81 (20.5%) of the participants exhibited good practice regarding Ai-PCA. Participation in Ai-PCA training showed a significant correlation with knowledge, attitude and practice scores. Besides, age, years of experience and professional titles of anesthesiologists were correlated with knowledge scores. The title of the anesthesiologist was associated with attitude scores. And the marital status of anesthesiologists was correlated with practice scores. CONCLUSION: Our findings revealed the score of practice regarding Ai-PCA are very poor among anesthesiologists in east China's Jiangsu Province. The utilization of Ai-PCA was found to be impacted by whether the individual had received training. This calls for a comprehensive approach should be conducted for raising the level of knowledge, attitude, and practice of anesthesiologist on using Ai-PCA and more Ai-PCA training to be included in the daily learning. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org.cn ; 27/10/2023; ChiCTR2300077070).

Assuntos

Analgesia Controlada pelo Paciente , Anestesiologistas , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Transversais , China , Masculino , Feminino , Adulto , Analgesia Controlada pelo Paciente/métodos , Inquéritos e Questionários , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Inteligência Artificial , Dor Pós-Operatória/tratamento farmacológico

RESUMO

BACKGROUND: Onychomycosis (OM) is a common nail infection treated with amorolfine hydrochloride nail lacquer in China. Monitoring drug concentrations and using dermoscopy to evaluate treatment efficacy may provide new insights. OBJECTIVE: The study aims to analyse amorolfine concentrations in nails with mild to moderate OM, assess treatment outcomes using dermoscopy and explore factors influencing drug concentrations and efficacy. METHODS: Patients with mild to moderate OM confirmed by fungal microscopy were enrolled. Amorolfine nail lacquer was applied twice weekly for 36 weeks. Monthly nail samples measured amorolfine concentrations using liquid chromatography. Dermoscopy was performed before and after treatment to evaluate responses. Mixed-effects models and logistic regression analysed factors affecting drug concentrations and outcomes. RESULTS: Ninety-seven nails were included. Amorolfine concentrations increased over time, with higher levels in females, fingernails, 2nd-5th digits and superficial white OM (p < 0.05). Age was a risk factor, while drug concentration and OM type were protective for clinical efficacy (p < 0.05). Peak concentration correlated with clinical (r = 0.487, p = 0.000) and mycological (r = 0.433, p = 0.000) responses. Dermoscopic features improved significantly in successful cases (p < 0.05). LIMITATIONS: In the assessment of fungal efficacy, only fungal microscopy was used, and fungal cultures were not performed. The study was limited by a small sample size and the lack of a longer follow-up to assess relapse. CONCLUSION: Amorolfine concentrations vary with patient and nail characteristics, influencing efficacy. Dermoscopy is valuable for monitoring OM treatment.

Assuntos

Antifúngicos , Morfolinas , Unhas , Onicomicose , Humanos , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Resultado do Tratamento , Morfolinas/uso terapêutico , Morfolinas/administração & dosagem , Unhas/microbiologia , Idoso , Adulto Jovem , Modelos Logísticos , China , Dermoscopia , Análise Multivariada , Adolescente

RESUMO

5-Aminolevulinic acid (5-ALA) is an endogenous non-protein amino acid and has been used as a new type of growth promoter in aquaculture feed. This study explored the effects of 5-ALA on growth and intestinal health in juvenile shrimp, Litopenaeus vannamei. Shrimps were fed diets containing five different 5-ALA levels (0, 15, 30, 45, and 60 g/t) for 90 days. A concentration of 45 g/t 5-ALA significantly improved growth metrics, including the specific growth rate, protein efficiency, and feed conversion (P < 0.05). The optimal concentration of 5-ALA was 38.3 g/t, as indicated by broken-line regression. Dietary supplementation with 5-ALA increased the crude protein content of whole shrimp, but had no significant effect on the moisture, ash, or crude lipid content (P > 0.05). Suitable supplementation of 5-ALA (45 g/t, 60 g/t) improved the activities of the digestive enzymes alpha-amylase, pepsin, trypsin, and lipase, thus promoting digestion and absorption. Shrimp fed with 45 g/t 5-ALA had increased levels of essential amino acids in the muscles and a higher proportion of polyunsaturated fatty acids in the hepatopancreas. Supplementation with 45 or 60 g/t 5-ALA upregulated the expression of genes related to growth and molting, including chitinase, ecdysone receptor, retinoic X receptor, calcium/calmodulin-dependent protein kinase I, heat shock protein 60, and heat shock protein 70. Moreover, dietary supplementation with 5-ALA affected the abundance of intestinal flora, increased the number of beneficial bacteria, and improved intestinal health. These results indicated that 5-ALA may significantly benefit shrimp health and aquaculture productivity, providing a novel theoretical basis for further research into 5-ALA as a dietary supplement.

RESUMO

BACKGROUND: The prevention of coronary artery disease (CAD) faces dual challenges: the aspirin-induced gastrointestinal injury, and the residual cardiovascular risk after statin treatment. Geraniol acetate (Gefarnate) is an anti-ulcer drug. It was reported that geraniol might participate in lipid metabolism through a variety of pathways. The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia. METHODS: In this prospective, open-label, randomized, controlled trial, 69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group, received gefarnate (100 mg/3 times a day) combined with statin and statin alone, respectively. At baseline and after one-month treatment, the levels of plasma triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol were tested. RESULTS: After one-month gefarnate treatment, triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L (P = 0.0018), LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L (P = 0.0004), HDL-C level increased from 0.97 mmol/L to 1.17 mmol/L (P = 0.0228). Based on statin therapy, gefarnate could significantly reduce the plasma triglyceride level (P = 0.0148) and increase the plasma HDL-C level (P = 0.0307). Although the LDL-C and total cholesterol levels tended to decrease, there was no statistically significant difference. CONCLUSIONS: The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia. This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

RESUMO

The accumulation of heavy metal in circulating TCMs has attracted widespread attention because the security and therapeutic efficacy are inevitably imperiled by the survival ecological environment and human production activities. How to reduce the pollution level and improve the toxicity damage becomes an urgent issue. This article provides a comprehensive overview of the current status of heavy metal contamination over a thousand types of single herbal (botanical, animal and mineral medicines) and TCM preparations published over nearly two decades. The survey revealed that growth ecosystems (soil, water sources), anthropogenic factors (harvesting, processing, storage), specific varieties and medicinal parts utilized as well as the inherent resistance capacity are the key factors that affect the accumulation of heavy metals in TCMs. And Pb, Cu and Cr are the major cumulative elements for botanicals, while mineral and animal medicines are dominated by As and Cu elements, respectively. Ongoing efforts aimed at mitigating the level and translocation rate of heavy metals by optimized cultivation processes, appropriate processing methodologies and advanced adsorption techniques are effective removal strategies. And the prospects of TCMs as a detoxifying agent for heavy metal toxicity damage posed development potential. Besides, the correlation between the speciation of arsenic (As) and chromium (Cr) and their toxicity should also be elaborated in order to provide effective references for standardizing drug dosage and cycle. And the imperative from the perspective of improving limitations standards of HMs for animal medicines, external preparations and folk medicines as well as exploring the interaction mechanisms between heavy metals and active ingredients of TCMs provides the direction for the follow-up study.

Assuntos

Medicina Tradicional Chinesa , Metais Pesados , Metais Pesados/análise , Medicamentos de Ervas Chinesas , Contaminação de Medicamentos , Poluição Ambiental , Monitoramento Ambiental , Humanos

RESUMO

Skin aging has been associated with the onset of various skin issues, and recent studies have identified an increase in Cdc42 activity in naturally aging mice. While previous literature has suggested that CASIN, a specific inhibitor of Cdc42 activity, may possess anti-aging properties, its specific effects on the epidermis and dermis, as well as the underlying mechanisms in naturally aging mice, remain unclear. Our study revealed that CASIN demonstrated the ability to increase epidermal and dermal thickness, enhance dermal-epidermal junction, and stimulate collagen and elastic fiber synthesis in 9-, 15-, and 24-month-old C57BL/6 mice in vivo. Moreover, CASIN was found to enhance the proliferation, differentiation, and colony formation and restore the cytoskeletal morphology of primary keratinocytes in naturally aging skin in vitro. Furthermore, the anti-aging properties of CASIN on primary fibroblasts in aging mice were mediated by the ribosomal protein RPL4 using proteomic sequencing, influencing collagen synthesis and cytoskeletal morphology both in vitro and in vivo. Meanwhile, both subcutaneous injection and topical application exhibited anti-aging effects for a duration of 21 days. Additionally, CASIN exhibited anti-inflammatory properties, while reduced expression of RPL4 was associated with increased inflammation in the skin of naturally aging mice. Taken together, our results unveil a novel function of RPL4 in skin aging, providing a foundational basis for future investigations into ribosomal proteins. And CASIN shows promise as a potential anti-aging agent for naturally aging mouse skin, suggesting potential applications in the field.

RESUMO

To assess the association between the timing of postsurgical adjuvant chemotherapy and overall survival (OS) and disease-free survival (DFS) in patients with pancreatic cancer (PC). Literature search of PubMed, EMBASE, and Scopus databases was done for randomized controlled trials (RCTs) or observational studies (cohort studies, case-control studies), reporting outcomes of adult PC patients (aged 18 and above) who underwent surgery and received adjuvant chemotherapy at different time points after the operation. Pooled effect sizes were quantified and reported as hazard ratio (HR). The primary outcomes were OS and DFS. A random effects model to was used account for potential variability across studies. Sixteen studies were included. There was no significant difference between early and delayed initiation of adjuvant chemotherapy in terms of OS (HR 1.03, 95% CI: 0.98, 1.08) and DFS (HR 1.09, 95% CI: 0.91, 1.31). Subgroup analyses based on tumour stage, sample size, and the number of chemotherapeutic agents used did not reveal significant associations. Delayed initiation was associated with reduced OS in patients with well- to moderately differentiated tumours, with the confidence intervals approaching statistical significance (HR 1.12, 95% CI: 1.00,1.25). There was no significant association between the timing of postoperative adjuvant chemotherapy initiation and OS and DFS in patients with pancreatic cancer. These findings underscore the importance of optimizing treatment strategies and suggest that clinicians need to focus on other critical aspects such as drug selection, dosage, and patient-specific factors that might substantially impact treatment efficacy.

RESUMO

Solvent engineering is one of the most effective strategies to control perovskite film quality, which directly affects the performance of perovskite solar cells (PSCs). Here, we introduce volatile acetonitrile (ACN) into the traditional solvent system (i.e., N,N-dimethylformamide and N-methyl-2-pyrrolidone) to dilute the perovskite precursors from 1.43 M to lower concentration (0.6-0.8 M). The dilution strategy can effectively improve the stability of the precursor solution and maintain similar film quality and device performance as those with high solution concentration (1.43 M). Notably, the devices with low-concentration precursors (0.6-0.8 M) show efficiency of 20.85% and improved long-term (>1000 h) storage stability compared to the device with high precursor concentration by blade-coating. Meanwhile, the material cost can be reduced by more than 50% when diluting to 0.6-0.8 M. These results demonstrate a universal dilution method which can provide guidance for the research and development of low-cost and high stability PSCs.