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This work reports a molecular-scale capacitance effect of the double helical nucleic acid duplex structure for the first time. By quantitatively conducting large sample measurements of the electrostatic field effect using a type of high-accuracy graphene transistor biosensor, an unusual charge-transport behavior is observed in which the end-immobilized nucleic acid duplexes can store a part of ionization electrons like molecular capacitors, other than electric conductors. To elucidate this discovery, a cascaded capacitive network model is proposed as a novel equivalent circuit of nucleic acid duplexes, expanding the point-charge approximation model, by which the partial charge-transport observation is reasonably attributed to an electron-redistribution behavior within the capacitive network. Furthermore, it is experimentally confirmed that base-pair mismatches hinder the charge transport in double helical duplexes, and lead to directly identifiable alterations in electrostatic field effects. The bioelectronic principle of mismatch impact is also self-consistently explained by the newly proposed capacitive network model. The mesoscopic nucleic acid capacitance effect may enable a new kind of label-free nucleic acid analysis tool based on electronic transistor devices. The in situ and real-time nucleic acid detections for virus biomarkers, somatic mutations, and genome editing off-target may thus be predictable.
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Técnicas Biossensoriais , Grafite , Ácidos Nucleicos , Capacitância Elétrica , Grafite/química , Transistores EletrônicosRESUMO
Heat stroke (HS) is a life-threatening systemic disease characterized by an elevated core body temperature of more than 40 â and subsequent multiple organ dysfunction syndrome. With the growing frequency of global heatwaves, the incidence rate of HS has increased significantly, which has caused a huge burden on people's lives and health. Liver injury is a well-documented complication of HS and usually constitutes the direct cause of patient death. In recent years, a lot of research has been carried out on the pathogenesis and treatment strategies of HS-induced liver injury. In this review, we summarized the important pathogenesis of HS-induced liver injury that has been confirmed so far. In addition to the comprehensive effect of systemic factors such as heat cytotoxicity, coagulopathy, and systemic inflammatory response syndrome, excessive hepatocyte cell pyroptosis, dysfunction of Kupffer cells, abnormal expression of heat shock protein expression, and other factors are also involved in the pathogenesis of HS-induced liver injury. Furthermore, we have also established the current therapeutic strategies for HS-induced liver injury. Our study is of great significance in promoting the understanding of the pathogenesis and treatment of HS-induced liver injury.
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Transtornos da Coagulação Sanguínea , Doença Hepática Crônica Induzida por Substâncias e Drogas , Golpe de Calor , Humanos , Doença Hepática Crônica Induzida por Substâncias e Drogas/complicações , Golpe de Calor/complicações , Golpe de Calor/terapia , Golpe de Calor/patologia , Insuficiência de Múltiplos Órgãos/complicaçõesRESUMO
AIMS: To retrospectively compare the efficacy of transcatheter chemoembolization (TACE) plus percutaneous radiofrequency ablation (PRFA) (hereafter, TACE + PRFA) and laparoscopic radiofrequency ablation (LRFA) in the treatment of inoperable hepatocellular carcinoma (HCC). METHODS: From July 2014 to December 2017, 132 consecutive patients with inoperable HCC were treated with TACE + PRFA (n = 86) or LRFA (n = 46). Overall survival (OS) and recurrence-free survival (RFS) were analyzed using log-rank test and Cox regression analysis. Propensity score matched (PSM) analyses based on patient and tumor characteristics were also conducted. Additionally, we performed exploratory analyses to determine the effectiveness of TACE + PRFA and LRFA in clinically relevant subsets. RESULTS: The baseline characteristics of TACE + PRFA patients displayed relatively inferior liver status and a higher rate of BCLC-B disease. For unmatched patients, median OS (55.0 vs. 42.0 months; p = .019) and RFS (20.0 vs. 11.0 months; p < .001) were significantly longer in TACE + PRFA group than that in the LRFA group. After PSM, 39 matched pairs were identified. The difference in median OS (60.0 vs. 44.0 months; p = .009) and RFS (27.0 vs. 11.0 months; p < .001) between the two groups remained significant. Multivariate analysis in matched patients showed that treatment modality and response to initial treatment were significant predictors of OS and RFS, while recurrence after resection was an independent prognostic factor of OS. The benefits of TACE + PRFA were consistent across all the subgroups examined. The different treatments had shared a similar complication rate. CONCLUSIONS: Compared to LRFA, TACE + PRFA results in improved OS and RFS in patients not amenable to resection.
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Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Laparoscopia , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
MicroRNAs are small noncoding RNAs which regulate gene expression at the posttranscriptional level. miR-155 is encoded by the miR-155 host gene (miR155HG), also known as the noncoding B cell integration cluster (BIC). MicroRNAs are widely expressed in various hematopoietic cells and are involved in regulating the immune system. In this review, we summarized how miR-155 modulates specific immune cells and the regulatory role of miR-155 in sepsis. miR-155 is expressed by different populations of innate and adaptive immune cells and is involved in the regulation of development, proliferation, and function in these cells. Sepsis is associated with uncontrollable inflammatory responses, accompanied by unacceptably high mortality. Due to the inadequacy of diagnostic markers as well as treatment strategies, treating sepsis can be a huge challenge. So far, a large number of experiments have shown that the expression of miR-155 is increased at an early stage of sepsis and that this increase is positively correlated with disease progression and severity. In addition, by blocking the proinflammatory effects of miR-155, it can effectively improve sepsis-related organ injury, providing novel insights to identify potential biomarkers and therapeutic targets for sepsis. However, since most of the current research is limited to animal experiments, further clinical research is required to determine the function of miR-155 and its mechanism related to sepsis.
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MicroRNAs/metabolismo , Sepse/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Humanos , MicroRNAs/genética , Sepse/genéticaRESUMO
Sepsis-associated acute lung injury (ALI) is a clinically critical disease that carries a high mortality rate. The pathogenesis of sepsis-associated ALI has not yet been precisely elucidated and there is a lack of effective treatment. As a new endogenous docosahexaenoic acid (DHA)-derived lipid mediators, Maresin1 has a significant dual role of anti-inflammatory and promoting inflammation regression. In this study, we established the sepsis model by the cecal ligation and puncture method (CLP) to explore the effect of Maresin1 on sepsis-induced lung injury. We found that the intervention of Maresin1 could significantly attenuate the sepsis-induced inflammatory responses, characterized by the down-regulation of the level of IL-1ß, IL-6, TNF-α, MPO, etc. Maresin1 could also significantly decrease the number of neutrophils in lung tissue, thus improving the related lung injury indicators. Our experiment clarified that the protective effect of Maresin1 on sepsis-associated lung injury is closely related to its inhibition function of JAK2/STAT3 and MAPK/NF-κB signaling pathways. Our findings provide new research directions and therapeutic targets for sepsis-associated ALI.
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Lesão Pulmonar Aguda , Sepse , Humanos , Janus Quinase 2 , Pulmão/metabolismo , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Fator de Transcrição STAT3 , Sepse/complicações , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND Intrathecal dexmedetomidine (DEX) can improve the blockade of spinal anesthesia, but there is no clear conclusion on whether it has an effect on the fetus during cesarean section. Our meta-analysis evaluated the safety and efficacy of intrathecal DEX in cesarean delivery. MATERIAL AND METHODS We searched Cochrane, Embase, PubMed, and CBM for eligible studies, and used the Revised Cochrane Risk of Bias Tool (RoB 2.0) to assess the risk of bias of each study. RevMan was used for statistical analyses. We have registered this meta-analysis on PROSPERO (CRD42019120995). RESULTS The meta-analysis included 10 RCTs, but only 5 were prospectively registered. The results of preregistration studies, including the 1- or 5-min Apgar score (mean difference [MD], -0.03; 95% confidence intervals [CI], -0.16 to 0.10; P=0.64 or MD, 0.00; 95% CI, -0.09 to 0.09; P=1), the umbilical arterial oxygen or carbon dioxide partial pressure (MD, 0.90; 95% CI, -4.92 to 6.72; P=0.76 or MD, 1.20; 95% CI, -2.06 to 4.46; P=0.47), and the cord blood pH (MD, -0.01; 95% CI, -0.05 to 0.03; P=0.72), showed that intrathecal DEX had no significant difference in neonatal outcomes compared with placebo. In maternal outcomes, intrathecal DEX significantly prolonged postoperative pain-free period and reduced the incidence of postoperative shivering, which did not increase spinal anesthesia-associated adverse effects. CONCLUSIONS Intrathecal DEX is safe for the fetus during cesarean section and can improve the blockade effects of spinal anesthesia on puerperae.
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Raquianestesia , Cesárea , Feto/fisiologia , Índice de Apgar , Dexmedetomidina/efeitos adversos , Dexmedetomidina/farmacologia , Feminino , Feto/efeitos dos fármacos , Humanos , Recém-Nascido , Período Pós-Operatório , Gravidez , Resultado da Gravidez , Viés de Publicação , Risco , Estremecimento/efeitos dos fármacos , Escala Visual AnalógicaRESUMO
BACKGROUND: The comparative efficacy of ancillary drugs on sevoflurane related emergence agitation (EA) in children undergoing ophthalmic surgery remains controversial. METHODS: The databases were retrieved in an orderly manner from the dates of their establishment to October, 2018, including PubMed, The Cochrane Library and Web of Science, to collect randomized controlled trials (RCT) of different anesthetic drugs combined with sevoflurane for ophthalmic surgery. Then a network meta-analysis was conducted using R and Stata 12.0 softwares. RESULTS: The meta-analysis showed that, in reducing sevoflurane related EA, dexmedetomidine, ketamine, propofol, fentanyl, midazolam, sufentanil, remifentanil and clonidine were superior to placebo (P < 0.05). The network meta-analysis showed that the effects of ancillary drugs combine with sevoflurane in reducing risk of EA in children undergoing ophthalmic surgery was superior to placebo: dexmedetomidine (OR = 0.17, 95% CrI 0.12-0.22), ketamine (OR = 0.30, 95% CrI 0.11-0.49), propofol (OR = 0.24, 95% CrI 0.09-0.63), fentanyl (OR = 0.16, 95% CrI 0.08-0.56), midazolam (OR = 0.20, 95% CrI 0.09-0.40), sufentanil (OR = 0.27, 95% CrI 0.14-0.41), remifentanil (OR = 0.18, 95% CrI 0.08-0.54) and clonidine (OR = 0.14, 95% CrI 0.07-0.41). The SUCRA of placebo, dexmedetomidine, ketamine, propofol, fentanyl, midazolam, sufentanil, remifentanil, clonidine were respectively 0.26, 77.93, 27.71, 42.8, 69.43, 52.89, 59.83, 57.62 and 61.53%. CONCLUSIONS: The effects of dexmedetomidine combine with sevoflurane in reducing risk of emergence agitation in children undergoing ophthalmic surgery was superior to other drugs.
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Acatisia Induzida por Medicamentos/prevenção & controle , Período de Recuperação da Anestesia , Anestésicos Inalatórios/efeitos adversos , Sevoflurano/efeitos adversos , Analgésicos/uso terapêutico , Teorema de Bayes , Criança , Clonidina/uso terapêutico , Dexmedetomidina/uso terapêutico , Quimioterapia Combinada , Fentanila/uso terapêutico , Humanos , Ketamina/uso terapêutico , Midazolam/uso terapêutico , Metanálise em Rede , Procedimentos Cirúrgicos Oftalmológicos , Propofol/uso terapêutico , Agitação Psicomotora , Remifentanil/uso terapêutico , Sufentanil/uso terapêuticoRESUMO
OBJECTIVE: To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE). MATERIALS AND METHODS: HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment. RESULTS: RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed. CONCLUSION: RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.
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Quimioembolização Terapêutica , Neoplasias Hepáticas , Relaxina , Animais , Quimioembolização Terapêutica/métodos , Coelhos , Relaxina/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Doxorrubicina/administração & dosagem , Humanos , Terapia Combinada , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Metástase NeoplásicaRESUMO
Purpose: The purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM). Methods: From December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events. Results: Ninety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed. Conclusion: In patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.
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Consumed VOCs are the compounds that have reacted to form ozone and secondary organic aerosol (SOA) in the atmosphere. An approach that can apportion the contributions of primary sources and reactions to the consumed VOCs was developed in this study and applied to hourly VOCs data from June to August 2022 measured in Shijiazhuang, China. The results showed that petrochemical industries (36.9 % and 51.7 %) and oxidation formation (20.6 % and 35.6 %) provided the largest contributions to consumed VOCs and OVOCs during the study period, whereas natural gas (5.0 % and 7.6 %) and the mixed source of liquefied petroleum gas and solvent use (3.1 % and 4.2 %) had the relatively low contributions. Compared to the non-O3 pollution (NOP) period, the contributions of oxidation formation, petrochemical industries, and the mixed source of gas evaporation and vehicle emissions to the consumed VOCs during the O3 pollution (OP) period increased by 2.8, 3.8, and 9.3 times, respectively. The differences in contributions of liquified petroleum gas and solvent use, natural gas, and combustion sources to consumed VOCs between OP and NOP periods were relatively small. Transport of petrochemical industries emissions from the southeast to the study site was the primary consumed pathway for VOCs emitted from petrochemical industries.
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BACKGROUND: The goal of the research was to examine the value of peripheral blood indicators in forecasting survival and recurrence among people suffering central-type non-small cell lung cancer (NSCLC) undergoing sleeve lobectomy (SL). METHODS: Clinical information was gathered from 146 individuals suffering from NSCLC who had SL at our facility between January 2014 and May 2023. Peripheral blood neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR) levels were determined by receiver operating characteristic (ROC) curve to establish the threshold points. Kaplan-Meier survival analysis was employed to evaluate the prognostic value of different groupings, and both univariate and multivariate Cox proportional hazards model (referred to as COX) were performed. RESULTS: The disease-free survival (DFS) and overall survival (OS) cutoff values were carried out via ROC analysis. Kaplan-Meier survival analysis revealed notable differences in OS for NLR (≥2.196 vs. <2.196, p = 0.0009), MLR (≥0.2763 vs. <0.2763, p = 0.0018), and PLR (≥126.11 vs. <126.11, p = 0.0354). Similarly, significant differences in DFS were observed for NLR (≥3.010 vs. <3.010, p = 0.0005), MLR (≥0.2708 vs. <0.2708, p = 0.0046), and PLR (≥126.11 vs. <126.11, p = 0.0028). Univariate Cox analysis showed that NLR (hazard ratio [HR]: 2.469; 95% confidence interval [CI]: 1.416-4.306, p < 0.001), MLR (HR: 2.192, 95% CI: 1.319-3.643, p = 0.002) and PLR (HR: 1.696, 95% CI: 1.029-2.795, p = 0.038) were correlated alongside OS. Multivariate Cox analysis showed that NLR (HR: 2.036, 95% CI: 1.072-3.864, p = 0.030) was a separate OS risk variable. Additionally, the pN stage (HR: 3.163, 95% CI: 1.660-6.027, p < 0.001), NLR (HR: 2.530, 95% CI: 1.468-4.360, p < 0.001), MLR (HR: 2.229, 95% CI: 1.260-3.944, p = 0.006) and PLR (HR: 2.249, 95% CI: 1.300-3.889, p = 0.004) were connected to DFS. Multivariate Cox analysis showed that pN stage (HR: 3.098, 95% CI: 1.619-5.928, p < 0.001) was a separate DFS risk variable. CONCLUSION: The study demonstrates that NLR, MLR, and PLR play a convenient and cost-effective role in predicting survival and recurrence among individuals alongside central-type NSCLC having SL.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfócitos , Neutrófilos , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Masculino , Feminino , Prognóstico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Neutrófilos/patologia , Linfócitos/patologia , Idoso , Plaquetas/patologia , Pneumonectomia/métodos , Monócitos , Adulto , Estudos Retrospectivos , Contagem de LinfócitosRESUMO
BACKGROUND: Primary thymic adenocarcinoma (PTAC) is an extremely rare disease with a poor prognosis. In the present study, we sought to analyze the clinical characteristics and prognostic factors of patients with PTAC. METHODS: A total of 14 patients with PTAC treated at our center from January 2000 to January 2019 were included in this study. We retrospectively collected information on sex, age, history of smoking, family history of cancer, comorbidities, symptoms, imaging tests, serum tumor marker levels, tumor, node, metastasis (TNM) staging, and treatment records. Follow-up information was obtained by telephone interviews or outpatient clinic visit. Univariate and multivariate Cox regression analyses were performed to investigate the clinicopathological factors associated with survival. RESULTS: Among 14 patients with PTAC, there were five males and nine females, with an average age of 48.7 ± 9.3 years. A total of 23.1% of the patients had a history of smoking. The clinical symptoms of the patients were nonspecific and seven patients had elevated levels of serum tumor markers. Surgery was performed for nine patients, among which only four received R0 resection. The median survival time of the 14 patients was 16.0 months, and the 1-, 3- and 5-year survival rates were 57.1%, 35.7% and 21.4%, respectively. TNM stage was identified as an independent prognostic factor for PTAC patients (the median survival time of stage I-IIIA vs. stage IV was 44.0 months vs. 9.0 months, p = 0.002). CONCLUSIONS: PTAC is highly aggressive malignancy with poor prognosis. Surgical treatment is feasible, but R0 resection is challenging. TNM staging is significantly associated with patient survival.
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Adenocarcinoma , Neoplasias do Timo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Neoplasias do Timo/patologia , Neoplasias do Timo/mortalidade , Adenocarcinoma/patologia , Adulto , Taxa de Sobrevida , Estadiamento de NeoplasiasRESUMO
Although most source apportionments of VOCs use mixing ratios, about 23 % of published studies use mass concentrations. Thus, systematically exploring the changes in VOC source apportioned results caused by metric differences is important to assess the differences in key precursor apportionment results given the observed increases in O3 pollution situation. Different monitoring instruments measured hourly VOC volumetric concentrations in three typical Chinese cities (i.e., Qingdao, Shijiazhuang, and Zhumadian). Converting volumetric to mass concentrations under standard and/or actual temperature-pressure conditions, VOC values with different metrics were obtained. The impacts of different metrics on the source apportionments were then investigated. Compared to the positive matrix factorization of the volumetric data (VC-PMF), the VOC species concentrations with low relative molecular mass (RMM) in the factor profiles substantially decreased in mass data analyses (MC-PMF). However, those species with high RMM substantially increased. There were no substantial differences in the apportioned source contributions based on standard and actual condition mass concentrations. However, the high-low rankings of percent contributions apportioned using the volumetric and mass data produced substantial differences. Compared with the VC-PMF results, the percent contributions of sources dominated by species with low RMM (e.g., natural gas usage and mixed sources containing natural gas usage) apportioned by MC-PMF decreased, while those of sources that emitted high RMM species (e.g., solvent usage and mixed sources containing solvent usage) increased. Source apportionments based on the volumetric concentration data had more practical significance compared to the mass concentration data results for control strategy development since the mass data analyses created issues.
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Poluentes Atmosféricos , Monitoramento Ambiental , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , China , Poluentes Atmosféricos/análise , Cidades , Poluição do Ar/estatística & dados numéricosRESUMO
Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation. Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay. Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1ß and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1ß also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1's protective effects in septic mice. Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.
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The immune response plays a pivotal role in the pathogenesis of diseases. Toll-like receptor 4 (TLR4), as an intrinsic immune receptor, exhibits widespread in vivo expression and its dysregulation significantly contributes to the onset of various diseases, encompassing cardiovascular disorders, neoplastic conditions, and inflammatory ailments. This comprehensive review centers on elucidating the architectural and distributive characteristics of TLR4, its conventional signaling pathways, and its mode of action in diverse disease contexts. Ultimately, this review aims to propose novel avenues and therapeutic targets for clinical intervention.
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Doenças Cardiovasculares , Receptor 4 Toll-Like , HumanosRESUMO
Purpose: This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors. Methods: Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery. Results: The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) (P <0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C (P <0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (P<0.05). The incidence of hypotension and tachycardia in group Es was lower than in group C (P <0.05). The NRS pain score at 3 d after surgery in group Es was lower than in group C (P <0.05). Conclusion: Low-dose esketamine infusion reduced to some extent the incidence of DNR in elderly patients undergoing general anesthesia for gastrointestinal tumors, improved intraoperative hemodynamics and BIS value, decreased the incidence of cardiovascular adverse events and the intraoperative consumption of opioids, and relieved postoperative pain.
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Delírio , Neoplasias Gastrointestinais , Humanos , Idoso , Remifentanil , Anestesia Geral/efeitos adversos , Dor Pós-Operatória , Neoplasias Gastrointestinais/cirurgiaRESUMO
BACKGROUND: Early recognition of the risk of acute respiratory distress syndrome (ARDS) after cardiopulmonary bypass (CPB) may improve clinical outcomes. The main objective of this study was to identify proteomic biomarkers and develop an early prediction model for CPB-ARDS. METHODS: The authors conducted three prospective nested cohort studies of all consecutive patients undergoing cardiac surgery with CPB at Union Hospital of Tongji Medical College Hospital. Plasma proteomic profiling was performed in ARDS patients and matched controls (Cohort 1, April 2021-July 2021) at multiple timepoints: before CPB (T1), at the end of CPB (T2), and 24 h after CPB (T3). Then, for Cohort 2 (August 2021-July 2022), biomarker expression was measured and verified in the plasma. Furthermore, lung ischemia/reperfusion injury (LIRI) models and sham-operation were established in 50 rats to explore the tissue-level expression of biomarkers identified in the aforementioned clinical cohort. Subsequently, a machine learning-based prediction model incorporating protein and clinical predictors from Cohort 2 for CPB-ARDS was developed and internally validated. Model performance was externally validated on Cohort 3 (January 2023-March 2023). RESULTS: A total of 709 proteins were identified, with 9, 29, and 35 altered proteins between ARDS cases and controls at T1, T2, and T3, respectively, in Cohort 1. Following quantitative verification of several predictive proteins in Cohort 2, higher levels of thioredoxin domain containing 5 (TXNDC5), cathepsin L (CTSL), and NPC intracellular cholesterol transporter 2 (NPC2) at T2 were observed in CPB-ARDS patients. A dynamic online predictive nomogram was developed based on three proteins (TXNDC5, CTSL, and NPC2) and two clinical risk factors (CPB time and massive blood transfusion), with excellent performance (precision: 83.33%, sensitivity: 93.33%, specificity: 61.16%, and F1 score: 85.05%). The mean area under the receiver operating characteristics curve (AUC) of the model after 10-fold cross-validation was 0.839 (95% CI: 0.824-0.855). Model discrimination and calibration were maintained during external validation dataset testing, with an AUC of 0.820 (95% CI: 0.685-0.955) and a Brier Score of 0.177 (95% CI: 0.147-0.206). Moreover, the considerably overexpressed TXNDC5 and CTSL proteins identified in the plasma of patients with CPB-ARDS, exhibited a significant upregulation in the lung tissue of LIRI rats. CONCLUSIONS: This study identified several novel predictive biomarkers, developed and validated a practical prediction tool using biomarker and clinical factor combinations for individual prediction of CPB-ARDS risk. Assessing the plasma TXNDC5, CTSL, and NPC2 levels might identify patients who warrant closer follow-up and intensified therapy for ARDS prevention following major surgery.
Assuntos
Ponte Cardiopulmonar , Síndrome do Desconforto Respiratório , Humanos , Animais , Ratos , Estudos de Coortes , Estudos Prospectivos , Ponte Cardiopulmonar/efeitos adversos , Proteômica , Biomarcadores , Síndrome do Desconforto Respiratório/etiologia , Isomerases de Dissulfetos de ProteínasRESUMO
Background: Acute respiratory distress syndrome (ARDS) remains a challenge because of its high morbidity and mortality. Circulation histones levels in ARDS patients were correlated to disease severity and mortality. This study examined the impact of histone neutralization in a rat model of acute lung injury (ALI) induced by a lipopolysaccharide (LPS) double-hit. Methods: Sixty-eight male Sprague-Dawley rats were randomized to sham (N = 8, received saline only) or LPS (N = 60). The LPS double-hit consisted of a 0.8 mg/kg intraperitoneal injection followed after 16 h by 5 mg/kg intra-tracheal nebulized LPS. The LPS group was then randomized into five groups: LPS only; LPS +5, 25, or 100 mg/kg intravenous STC3141 every 8 h (LPS + L, LPS + M, LPS + H, respectively); or LPS + intraperitoneal dexamethasone 2.5 mg/kg every 24 h for 56 h (LPS + D). The animals were observed for 72 h. Results: LPS animals developed ALI as suggested by lower oxygenation, lung edema formation, and histological changes compared to the sham animals. Compared to the LPS group, LPS + H and +D groups had significantly lower circulating histone levels and lung wet-to-dry ratio, and the LPS + D group also had lower BALF histone concentrations; the blood neutrophils and platelets counts in LPS + D group did not change, meanwhile, the LPS + L, +M and +H groups had significantly lower neutrophil counts and higher platelet counts in the blood; the total number of BALF WBC, platelet counts, MPO and H3 were significantly lower in the LPS + L, +M, +H and +D groups than in the LPS only group; and the degree of inflammation was significantly less in the LPS + L, +M, +H and +D groups, moreover, inflammation in the LPS + L, +M and +H animals showed a dose-dependent response; finally, the LPS + L, +M, +H and +D groups had improved oxygenation compared to the LPS group, and there were no statistical differences in PCO2 or pH among groups. All animals survived. Conclusion: Neutralization of histone using STC3141, especially at high dose, had similar therapeutic effects to dexamethasone in this LPS double-hit rat ALI model, with significantly decreased circulating histone concentration, improved acute lung injury and oxygenation.
RESUMO
Detection of multiple analytes simultaneously in small liquid samples with high efficiency and precision is highly important to the fields like water quality monitoring. In this letter, we present a multiplexed nanosensors with position-encoded aptamer functionalized gold nanorods for heavy metal ions detection. The individual gold nanorods respond specifically to two different heavy metal ions (Pb2+ and Hg2+) with a spectral shift in the scattering spectrum. We used a home-built spectral imaging dark-field microscope to measure the response of thousands of single plasmonic nanosensors with relatively high time resolution and precision. To explore the performance and limit of detection (LOD) of our nanosensor and setup, we recorded the concentration-dependent response of our position-encoded nanosensors with a series of mixture solutions that contain different concentrations of Hg2+ and Pb2+ ions. The LOD levels of our system are around 5 nM for Pb2+ ions and 1 nM for Hg2+ ions. Our method and results demostrate the nanomolar sensitivity and the potential to detect more different heavy metal ions.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Metais Pesados , Ouro , ÍonsRESUMO
Acute lung injury (ALI) is the most common type of organ injury in sepsis, with high morbidity and mortality. Sepsis is characterized by an inappropriate inflammatory response while neutrophils exert an important role in the excessive inflammatory response. The discovery of specialized pro-resolving mediators (SPMs) provides a new direction for the treatment of a series of inflammatory-related diseases including sepsis. Among them, the regulation of Maresin1 on immune cells was widely demonstrated. However, current research on the regulatory effects of Maresin1 on immune cells has remained at the level of certain cell types. Under inflammatory conditions, the immune environment is complex and immune cells exhibit obvious heterogeneity. Neutrophils play a key role in the occurrence and development of septic lung injury. Whether there is a subpopulation bias in the regulation of neutrophils by Maresin1 has not been elucidated. Therefore, with the well-established cecal ligation and puncture (CLP) model and single-cell sequencing technology, our study reveals for the first time the regulatory mechanism of Maresin1 on neutrophils at the single-cell level. Our study suggested that Maresin1 can significantly reduce neutrophil infiltration in septic lung injury and that this regulatory effect is more concentrated in the Neutrophil-Cxcl3 subpopulation. Maresin1 can significantly reduce the infiltration of the Neutrophil-Cxcl3 subpopulation and inhibit the expression of related inflammatory genes and key transcription factors in the Neutrophil-Cxcl3 subpopulation. Our study provided new possibilities for specific modulation of neutrophil function in septic lung injury.