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1.
J Am Chem Soc ; 146(36): 25312-25320, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39219059

RESUMO

A highly efficient Ru-catalyzed asymmetric hydrogenation of α,ß-unsaturated γ-lactams has been developed by using a C2-symmetric ruthenocenyl phosphine-oxazoline as the chiral ligand. This method achieves the enantioselective synthesis of chiral ß-substituted γ-lactams in high yields and with excellent enantioselectivities (up to 99% yield with 99% ee). Mechanistic studies based on detailed control experiments and computational investigation revealed that the cationic Ru-complex acts as the active catalytic species; the protonation process of the oxa-π-allyl-Ru complex, which is formed by the migratory insertion of the C=C double bond to the Ru-H bond (the stereocontrolling step) followed by an isomerization process, is the rate-determining step, and the existence of PPh3 is crucial for the highly efficient catalytic behavior. The protocol provides a straightforward and practical pathway for the synthesis of key intermediates for several chiral drugs and bioactive compounds, particularly for the 150 kg-scale industrial production of Brivaracetam, an antiepileptic drug that shows 13-fold more potent binding to the synaptic vesicle protein 2A compared with the well-known Levetiracetam.

2.
Small ; 19(10): e2205607, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36585387

RESUMO

Aggredation-induced electrochemiluminescence (AIECL) promises an efficient strategy for synthesize highly luminescent emitter and co-reactant for ECL analysis, however, rational control of electrogenerated emission intensity is still challenging. The low electroconductivity and amorphous molecular configuration are intrinsic bottleneck. This work reveals the impact of polyvinyl pyrrolidone backbone regulated silver nanocrystallines (AgNCs/PVP) on the cathode AIECL properties in near infrared region, by employing the Box-Behnken designed response surface computation model to modulate crystal aggregates. Electron paramagnetic resonance spectroscopy discovered hydrogen radical (HO• ) dominant reductive-oxidative (R-O) ECL mechanism with AgNCs acting as the co-reaction accelerator in graphene oxide/persulfate system (GO/S2 O8 2- ). Both theoretical calculation and experimental measurement testified that the ECL of AgNCs in GO/S2 O8 2- dependent on the concentration of in situ electrochemical oxidized Ag+ . The high efficiency of crystallization-induced enhanced ECL (CIECL) originates from 1) the effective electron transfer of Ag+ accelerated HO• produce to notable promote radioactive transition, and 2) twisted intramolecular charge transfer from the electron-rich donor of PVP to electron-deficient receptor of Ag0 to restrict nonradioactive transition. The AgNCs/PVP with CIECL effect are applied to construct an ultrasensitive platform for miR-221 assay with a lower detection limit of 7.47 × 103  copies mL-1 than typical qPCR method.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Medições Luminescentes/métodos , Cristalização , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Limite de Detecção , Eletrodos , Nanopartículas Metálicas/química
3.
J Craniofac Surg ; 34(8): 2540-2543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38011269

RESUMO

BACKGROUND: Tumors in the petroclival region have challenged neurosurgeons. However, neuroendoscopy has been increasingly applied internationally. This study simulated a pure neuroendoscopic transfarlateral supracerebellar infratentorial approach for petroclival tumor resection from the cadaveric head and discussed the advantages and safety of this approach. METHODS: The anatomical structure for petroclival tumor resection was visualized using a pure neuroendoscopic transfarlateral supracerebellar infratentorial approach in 5 cadaveric heads. Ten cases with petroclival tumors were retrospectively analyzed and summarized between January 2020 and June 2021. All the cases had undergone surgery using a pure neuroendoscopic supracerebellar infratentorial approach. RESULTS: The anatomical structure of the petroclival region was exposed using the pure neuroendoscopic supracerebellar infratentorial approach, and the partial anatomical structure of the middle skull base was further exposed by incision of the tentorium in the cadaveric head. Among the 10 cases, the tumors of 6 cases were totally removed, and those of 4 cases were subtotally removed; no cases of intracranial infection or death occurred after surgery. CONCLUSION: The neuroendoscopic transfarlateral supracerebellar infratentorial keyhole approach is a safe and effective surgical method to treat petroclival lesions and invasive middle cranial fossa lesions.


Assuntos
Neoplasias , Neuroendoscopia , Humanos , Neuroendoscopia/métodos , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/métodos , Cadáver
4.
Mediators Inflamm ; 2022: 2298865, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248187

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease leading to inflammatory damage in multiple target organs, and lupus nephritis (LN) is one of the most life-threatening organ manifestations. CCAAT/enhancer-binding protein ß (CEBPB) regulates the NLRP3 inflammasome and is involved in the pathogenesis of SLE. However, the role and mechanism of CEBPB in LN remains unclear. MRL/lpr mice and lipopolysaccharides (LPS) combined with adenosine triphosphate- (ATP-) treated glomerular podocytes were used as models of LN in vivo and in vitro, respectively. In vivo, we investigated the expressions of CEBPB during the development of MRL/lpr mice. Then we assessed the effect of CEBPB inhibition on renal structure and function through injecting shCEBPB lentivirus into MRL/lpr mice. In vitro, glomerular podocytes were treated with Pim-1-OE and siCEBPB to explore the relation between CEBPB and Pim-1. The progression of LN in mice was associated with the increased level of CEBPB, and the inhibition of CEBPB ameliorated renal structure impairments and improved renal function damage associated with LN. Knockdown of CEBPB could suppress the activation of NLRP3 inflammasome and the secretion of IL-1ß and IL-6. Furthermore, the knockdown of CEBPB could inhibit NLRP3 inflammasome activation and pyroptosis via binding to Pim-1 promoter to downregulate its expression, and the overexpression of Pim-1 reversed the effects of CEBPB deficiency. The regulation of CEBPB on Pim-1 facilitated pyroptosis by activating NLRP3 inflammasome, thereby promoting the development of LN.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Trifosfato de Adenosina , Animais , Inflamassomos/metabolismo , Interleucina-6 , Lipopolissacarídeos/farmacologia , Nefrite Lúpica/metabolismo , Camundongos , Camundongos Endogâmicos MRL lpr , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/metabolismo
5.
Bioorg Med Chem ; 29: 115891, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278783

RESUMO

Ryanodine receptors (RyRs) are important ligand-gated Ca2+ channels; their excessive activation leads to Ca2+ leakage in the sarcoplasmic reticulum that may cause neurological diseases. In this study, three series of novel potent RyR1 inhibitors based on dantrolene and bearing semicarbazone and imidazolyl moieties were designed and synthesized, and their biological activity was evaluated. Using a single-cell calcium imaging method, the calcium overload inhibitory activities of 26 target compounds were tested in the R614C cell line, using dantrolene as a positive control. The preliminary investigation showed that compound 12a suppressed Ca2+ release as evidenced by store overload-induced Ca2+release (SOICR) (31.5 ± 0.1%, 77.2 ± 0.1%, 93.7 ± 0.2%) at 0.1 µM, 3 µM and 10 µM, respectively. Docking simulation results showed that compound 12a could bind at the active site of the RyR1 protein. The Morris water-maze test showed that compound 12a significantly improved the cognitive behavior of AD-model mice. Further studies on the structural optimization of this series of derivatives are currently underway in our laboratory.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/síntese química , Fármacos Neuroprotetores/síntese química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Semicarbazonas/síntese química , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio , Dantroleno/química , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Imidazóis/química , Masculino , Camundongos , Simulação de Acoplamento Molecular , Teste do Labirinto Aquático de Morris , Fármacos Neuroprotetores/farmacologia , Ligação Proteica , Conformação Proteica , Semicarbazonas/farmacologia , Análise de Célula Única , Relação Estrutura-Atividade
6.
BMC Pregnancy Childbirth ; 21(1): 40, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422023

RESUMO

BACKGROUND: Maternal admission to the intensive care unit (ICU) during pregnancy or in the postpartum period is a marker of severe acute maternal morbidity. Mechanical ventilation is an important and basic method of maintaining life support in the ICU, but prolonged mechanical ventilation (PMV) is associated with a prolonged length of hospital stay and other adverse outcomes. Therefore, we conducted this retrospective study to describe morbidity and further try to identify the risk factors for PMV in critically ill obstetric women. METHODS: The clinical data were obtained from a single-centre retrospective comparative study of 143 critically ill obstetric patients at a tertiary teaching hospital in mainland China between January 1, 2009, and December 31, 2019. PMV was defined as a mechanical ventilation length of more than 24 h. Clinical and obstetric parameters were collected to analyse the risk factors for PMV. Patients were separated into groups with and without PMV. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of PMV. RESULTS: Out of 29,236 hospital deliveries, 265 critically ill obstetric patients entered the ICU. One hundred forty-five (54.7%) of them were treated with mechanical ventilation. Two were excluded because of death within 24 h. Sixty-five critically ill obstetric patients (45.5%) underwent PMV. The independent risk factors for PMV included estimated blood loss (odds ratio (OR) =1.296, P=0.029), acute kidney injury (AKI) (OR=4.305, P=0.013), myocardial injury (OR=4.586, P=0.012), and PaO2/FiO2 (OR=0.989, P< 0.001). The area under the receiver operating characteristic (ROC) curve based on the predicted probability of the logistic regression was 0.934. CONCLUSIONS: Estimated blood loss, AKI, myocardial injury, and PaO2/FiO2 were independent risk factors for PMV in critically ill obstetric patients.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Complicações na Gravidez/terapia , Respiração Artificial/estatística & dados numéricos , Injúria Renal Aguda/complicações , Adulto , China , Estado Terminal/epidemiologia , Estado Terminal/terapia , Métodos Epidemiológicos , Feminino , Traumatismos Cardíacos/complicações , Hospitais de Ensino/estatística & dados numéricos , Humanos , Tempo de Internação , Período Pós-Parto , Gravidez , Respiração Artificial/efeitos adversos , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo , Hemorragia Uterina/complicações
7.
Water Sci Technol ; 82(1): 120-130, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32910797

RESUMO

In order to investigate the effect of temperatures and operating modes on extracellular polymeric substances (EPS) contents, three sequencing batch reactors (SBRs) were operated at temperatures of 15, 25, and 35 °C (R15 °C, R25 °C, and R35 °C, respectively), with two SBRs operated under alternating anoxic/oxic conditions (RA/O and RO/A, respectively). Results showed that higher contents of tightly bound EPS (TB-EPS) and total EPS appeared in R15 °C, while loosely bound EPS (LB-EPS) dominated in R35 °C. In all three kinds of EPS (LB-EPS, TB-EPS and total EPS) assessed, protein was the main component in R15 °C and R25 °C, while polysaccharides dominated in R35 °C. Moreover, compared with RO/A, RA/O was favorable for the production of the three kinds of EPS. Furthermore, three kinds of EPS and their components were augmented during the nitrification process, while they declined during the denitrification process under all conditions except for R35 °C.


Assuntos
Matriz Extracelular de Substâncias Poliméricas , Esgotos , Reatores Biológicos , Nitrificação , Temperatura
8.
Exp Cell Res ; 373(1-2): 91-98, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30308195

RESUMO

MiR-182-5p suppresses expression of Foxo1 that is a protective factor in renal disorders and is up-regulated in systemic lupus erythematosus patients. Thus, we hypothesized that dys-function of miR-182-5p/Foxo1 axis contributed to development of lupus nephritis (LN). Firstly, we investigated the expressions of miR-182-5p and Foxo1 in LN patients and during growth of LN MRL/lpr mice. Then we subjected MRL/lpr mice to the injection of miR-182-5p antagomirs and assessed the effect of miR-182-5p inhibition on renal structure and function. In vitro, we administrated renal cell lines with TGF-ß1 to explore the relation between renal fibrosis and miR-182-5p. The level of miR-182-5p was up-regulated in high Chronicity Index patients while the level of Foxo1 was suppressed. The progression of LN in mice was associated with the increased level of miR-182-5p and the decreased level of Foxo1. The inhibition of miR-182-5p ameliorated renal structure and function impairments associated with LN, along with the increased expression of Foxo1. The administration of TGF-ß1 in vitro increased the expression of miR-182-5p in renal cells in an overall dose-dependent manner. The current study demonstrated that the expression of miR-182-5p was increased in LN patients, contributing to the suppression of Foxo1 and development of LN.


Assuntos
Proteína Forkhead Box O1/metabolismo , Nefrite Lúpica/genética , MicroRNAs/antagonistas & inibidores , Animais , Células Cultivadas , Progressão da Doença , Feminino , Humanos , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Camundongos Endogâmicos MRL lpr , MicroRNAs/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/farmacologia
9.
Cell Physiol Biochem ; 40(6): 1570-1577, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27997905

RESUMO

BACKGROUND/AIMS: Prior studies demonstrate that hypoxia inducible factor subtype 1α (HIF-1α) in retinal tissues is involved in development of diabetic retinopathy (DR). In this report, we particularly examined the role played by mammalian target of rapamycin (mTOR) in regulating expression of HIF-1α and its downstream pathway, namely vascular endothelial growth factor (VEGF). METHODS: Streptozotocin (STZ) was systemically injected to induce hyperglycemia in rats. ELISA and Western Blot analysis were employed to determine the levels of HIF-1α and VEGF as well as expression of mTOR pathways in retinal tissues of control rats and STZ rats. RESULTS: Our results show that HIF-1α and VEGF as well as VEGF receptor subtype 2 (VEGFR-2) were increased in STZ rats. Also, the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in diabetic retina compared with controls. Blocking mTOR by using rapamycin significantly attenuated activities of HIF-1α and VEGF signaling pathways. CONCLUSION: Our data for the first time revealed specific signaling pathways engaged in the development of DR, including the activation of mTOR and HIF-1α -VEGF mechanism. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of DR often observed in clinics.


Assuntos
Retinopatia Diabética/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Glicemia/metabolismo , Caspase 3/metabolismo , Retinopatia Diabética/patologia , Masculino , Ratos Sprague-Dawley , Retina/metabolismo , Retina/patologia , Estreptozocina , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
10.
Biochem Biophys Res Commun ; 461(3): 555-9, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-25912142

RESUMO

The epithelial barrier is critical in the maintenance of the homeostasis of the cornea. A number of eye disorders are associated with the corneal epithelial barrier dysfunction. Viral infection is one common eye disease type. This study aims to elucidate the mechanism by which the activation of toll like receptor 3 (TLR3) in the disruption of the corneal epithelial barrier. In this study, HCE cells (a human corneal epithelial cell line) were cultured into epithelial layers using as an in vitro model of the corneal epithelial barrier. PolyI:C was used as a ligand of TLR3. The transepithelial electric resistance (TER) and permeability of the HCE epithelial layer were assessed using as the parameters to evaluate the corneal epithelial barrier integrity. The results showed that exposure to PolyI:C markedly decreased the TER and increased the permeability of the HCE epithelial layers; the levels of cell junction protein, E-cadherin, were repressed by PolyI:C via increasing histone deacetylase-1 (HDAC1), the latter binding to the promoter of E-cadherin and repressed the transcription of E-cadherin. The addition of butyrate (an inhibitor of HDAC1) to the culture blocked the corneal epithelial barrier dysfunction caused by PolyI:C. In conclusion, activation of TLR3 can disrupt the corneal epithelial barrier, which can be blocked by the inhibitor of HDAC1.


Assuntos
Epitélio Corneano/fisiopatologia , Receptor 3 Toll-Like/metabolismo , Sequência de Bases , Linhagem Celular , Células Cultivadas , Imunoprecipitação da Cromatina , Primers do DNA , Epitélio Corneano/enzimologia , Epitélio Corneano/metabolismo , Histona Desacetilase 1/metabolismo , Humanos , Permeabilidade , Fosforilação , Poli I-C/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
11.
Clin Appl Thromb Hemost ; 30: 10760296241271358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39109998

RESUMO

Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC's association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.


Assuntos
Coagulação Intravascular Disseminada , Insuficiência de Múltiplos Órgãos , Sepse , Humanos , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/mortalidade , Sepse/complicações , Sepse/mortalidade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Mortalidade Hospitalar
12.
Heliyon ; 10(6): e27306, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38509987

RESUMO

Currently, stem cells are a prominent focus of regenerative engineering research. However, due to the limitations of commonly used stem cell sources, their application in therapy is often restricted to the experimental stage and constrained by ethical considerations. In contrast, urine-derived stem cells (USCs) offer promising advantages for clinical trials and applications. The noninvasive nature of the collection process allows for repeated retrieval within a short period, making it a more feasible option. Moreover, studies have shown that USCs have a protective effect on organs, promoting vascular regeneration, inhibiting oxidative stress, and reducing inflammation in various acute and chronic organ dysfunctions. The application of USCs has also been enhanced by advancements in biomaterials technology, enabling better targeting and controlled release capabilities. This review aims to summarize the current state of research on USCs, providing insights for future applications in basic and clinical settings.

13.
Heliyon ; 9(6): e16285, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37292294

RESUMO

We estimated the population density and quantified its characteristics using remote sensing, census data, and Geographic Information System (GIS). The interactive influence of these factors on population density was quantified based on geographic detectors to identify the differentiation mechanisms in the Chengdu metropolitan area of China. We identified the key factors that contribute to population density growth. The models used to simulate population density had the highest R2 values (>0.899). Population density tended to increase with time, with a multicentre spatial agglomeration pattern; the centre of gravity of the spatial distribution tended to move from the southeast to the northwest. Industry proportions, Normalised Difference Vegetation Index (NDVI), land use, distance to urban centers or construction land, and GDP per capita can satisfactorily explain population density changes. The combined impact of these elements on population density variation exhibited mutual and non-linear strengthening, with the mutual effect of the two elements intensifying the impact of each individual element. Our study identified the key driving forces that contribute to the differentiation of population density, which can provide valuable support for the development of effective regional and targeted population planning guidelines.

14.
World J Clin Cases ; 11(32): 7876-7880, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38073692

RESUMO

BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an uncommon subtype of squamous cell carcinoma (SCC) of the lung, closely associated with Epstein-Barr virus (EBV) infection. The pathological features of PPLELC closely resemble those of SCC, which makes it prone to misdiagnosis. Surgical intervention constitutes the primary treatment approach for PPLELC. CASE SUMMARY: This report describes a 44-year-old woman who was hospitalized for 1 mo due to left chest pain. Computed tomography revealed a mass shadow in the anterior basal segment of the left lower lobe, and a subsequent needle biopsy suggested SCC. The patient underwent radical tumor resection in the lower left lobe of the lung, and postoperative pathological examination indicated lymphoepithelial carcinoma, and the test for EBV encoded small RNA was positive. Following surgery, the patient was scheduled to receive four cycles of adjuvant chemotherapy, using the paclitaxel + carboplatin regimen, but the patient refused further treatment. CONCLUSION: PPLELC is an exceptionally rare subtype of lung SCC and is prone to misdiagnosis.

15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(12): 1241-1244, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38149383

RESUMO

OBJECTIVE: To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death. METHODS: A retrospective case-control study was conducted. Patients with septic shock admitted to emergency intensive care unit (EICU) and intensive care unit (ICU) in Peking University People's Hospital from April 1, 2015 to January 31, 2023 were enrolled. Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group, according to whether the minimum platelet count was less than 100×109/L within 24 hours after admission to ICU. The outcome index was the mortality during ICU stay. The baseline data, hospitalization information and laboratory test results of the two groups were compared, and the risk factors of in-hospital death were analyzed by Logistic regression, and the mediation effect was performed by Bootstrap method. RESULTS: A total of 301 patients with septic shock were enrolled, of which 172 (57.1%) had thrombocytopenia and 129 (42.9%) did not. There were significant differences between the two groups in age, mortality, disseminated intravascular coagulation (DIC), continuous renal replacement therapy, and level of creatinine, urea nitrogen, total bilirubin, white blood cell count, lymphocyte count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Univariate Logistic regression analysis showed thrombocytopenia [odds ratio (OR) = 4.478], continuous renal replacement therapy (OR = 4.601), DIC (OR = 6.248), serum creatinine (OR = 1.005), urea nitrogen (OR = 1.126), total bilirubin (OR = 1.006) and PT (OR = 1.126) were risk factors of death during hospitalization in patients with septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that thrombocytopenia [OR = 3.338, 95% confidence interval (95%CI) was 1.910-5.834, P = 0.000], continuous renal replacement therapy (OR = 3.175, 95%CI was 1.576-6.395, P = 0.001) and PT (OR = 1.077, 95%CI was 1.011-1.147, P = 0.021) were independent risk factors for in-hospital mortality in patients with septic shock. Mediation analysis showed that 51% of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy. CONCLUSIONS: Thrombocytopenia is a powerful predictor of death in septic shock patients, and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.


Assuntos
Sepse , Choque Séptico , Trombocitopenia , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Mortalidade Hospitalar , Prognóstico , Unidades de Terapia Intensiva , Bilirrubina , Nitrogênio , Ureia
16.
Curr Med Res Opin ; 39(2): 289-298, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36245361

RESUMO

OBJECTIVE: Lung squamous cell carcinoma (LUSC), one of the most common subtypes of lung cancer, is a leading cause of cancer-caused deaths in the world. It has been well demonstrated that a deep understanding of the tumor environment in cancer would be helpful to predict the prognosis of patients. This study aimed to evaluate the tumor environment in LUSC, and to construct an efficient prognosis model involved in specific subtypes. METHODS: Four expression files were downloaded from the Gene Expression Omnibus (GEO) database. Three datasets (GSE19188, GSE2088, GSE6044) were considered as the testing group and the other dataset (GSE11969) was used as the validation group. By performing LUSC immune subtype consensus clustering (CC), LUSC patients were separated into two immune subtypes comprising subtype 1 (S1) and subtype 2 (S2). Weighted gene co-expression network (WGCNA) and least absolute shrinkage and selection operator (LASSO) were performed to identify and narrow down the key genes among subtype 1 related genes that were closely related to the overall survival (OS) of LUSC patients. Using immune subtype related genes, a prognostic model was also constructed to predict the OS of LUSC patients. RESULTS: It showed that LUSC patients in the S1 immune subtype exhibited a better OS than in the S2 immune subtype. WGCNA and LASSO analyses screened out important immune subtype related genes in specific modules that were closely associated with LUSC prognosis, followed by construction of the prognostic model. Both the testing datasets and validation dataset confirmed that the prognostic model could be efficiently used to predict the OS of LUSC patients in subtype 1. CONCLUSION: We explored the tumor environment in LUSC and established a risk prognostic model that might have the potential to be applied in clinical practice.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Bases de Dados Factuais , Pulmão , Prognóstico
17.
Anal Biochem ; 422(1): 7-13, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22230283

RESUMO

A new metal-organic nanocomposite with synergistic catalysis function was prepared and developed to construct an electrochemiluminescence (ECL) immunosensor for ultrasensitive detection of tumor biomarker CA125. Silver nanoparticles (AgNPs) and nicotinamide adenine dinucleotide hydride (NADH) that can participate and catalyze the ECL reaction of Ru(bpy)(3)(2+) were employed as the metal component and the organic component to synthesize the metal-organic nanocomposite of NADH-AgNPs (NA). The novel ECL immunosensor was assembled via Ru(bpy)(3)(2+)-doped silica nanoparticles (Ru-SiO(2)) modified electrode with the NA as immune labels. First, the chitosan-suspended Ru-SiO(2) nanoparticles were cast on the gold electrode surface to immobilize the ECL probes of Ru(bpy)(3)(2+) and link gold nanoparticles. Then, the primary antibodies were loaded onto the modified electrode via the gold sulfhydryl covalent binding. After immunobinding the analytes of antigen, NA-attached secondary antibodies could be captured as a sandwich type on the electrode. Finally, based on the circularly synergistic catalysis by the silver and NADH for the solid-phase ECL of Ru(bpy)(3)(2+), the proposed immunosensor sensed the concentration of antigen. The synergistic ECL catalysis of metal-organic nanocomposite amplified response signal and pushed the detection limit down to 0.03 U ml(-1), which initiated a new ECL labeling field and has great significance for ECL immunoassays.


Assuntos
Técnicas Biossensoriais/métodos , Antígeno Ca-125/química , Medições Luminescentes/métodos , Proteínas de Membrana/química , Nanopartículas Metálicas/química , NAD/química , Prata/química , Biomarcadores Tumorais/química , Técnicas Biossensoriais/instrumentação , Antígeno Ca-125/análise , Antígeno Ca-125/sangue , Catálise , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Limite de Detecção , Proteínas de Membrana/análise , Proteínas de Membrana/sangue , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica , NAD/ultraestrutura , Nanocompostos/ultraestrutura
18.
Heliyon ; 8(11): e11389, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36387544

RESUMO

The land use degree reflects the land use due to natural factors and human activities, and thus, its spatial differentiation analysis and the study of factors influencing it is of great importance. Although the mechanisms by which changes in factors affect land use have been extensively studied, the impact of factor variations on spatial differentiation of land use degree remains poorly understood. Therefore, in this study, we applied geographical detector, a new tool of spatial statistics, and used spatial autocorrelation and GIS spatial analyses to study the interactive effects of factors on land use degree and their changes in Sichuan, western China and identified the most appropriate characteristics and scope of factors. The land use degree showed an increasing trend. The geographical differentiation of land use was significant, with a high land use degree in the Chengdu Plain and its surrounding areas in the east, a low land use degree in the plateau area of western Sichuan and a significant aggregated distribution. Topographic relief, elevation, annual average temperature, geomorphic type, ≥10°C accumulated temperature, and other factors provided a good explanation for the variability in the land use degree. There were interactive effects of factors that influenced the land use degree. The synergistic effects of factors exhibited mutual and non-linear enhancement relationships, and the interaction of the factors enhanced the influence of individual factors. The most appropriate characteristics and scope of the main factors revealed by our study will contribute to a better understanding of the influences of factors on the changes in land use and their driving mechanisms.

19.
Environ Sci Pollut Res Int ; 29(21): 32016-32031, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35015237

RESUMO

The influence of factors on vegetation changes in different regions is still largely unknown. We applied the geographic detector, a new spatial statistical method, to study the interactive effects of factors on the spatial patterns of normalised vegetation index (NDVI) changes and determine the optimal characteristics of key impact factors beneficial to vegetation growth. Our results show that from 2000 to 2015, the vegetation cover for the upper reaches of the Minjiang River, western China was in good condition. Furthermore, more than 80% of the areas had NDVI values ranging from 0.6 to 0.8 and NDVI > 0.8, and the spatial-temporal changes of vegetation cover were significant. The vegetation cover changes showed a significant transformation in the regions with NDVI > 0.6. Our study uniquely illustrated that elevation, annual average temperature and soil type can explain vegetation changes quite well. We propose that interactive effects exist among impact factors on vegetation NDVI, and the synergistic effects of the impact factors show mutual and nonlinear enhancements. The interactions among impact factors significantly enhance the impact of a single factor on vegetation changes. The most suitable characteristics of the main impact factors that promote vegetation growth were revealed by this study and will help improve our understanding of factors that impact NDVI and its driving mechanisms. Our findings suggest that the established favourable value range or the most suitable characteristics of impact factors will help management plans to intervene and promote vegetation change for vegetation restoration and alleviate environmental degradation.


Assuntos
Ecossistema , Rios , China , Monitoramento Ambiental , Geografia , Solo , Temperatura
20.
Front Genet ; 13: 895099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664332

RESUMO

Precise segmentation of chromosome in the real image achieved by a microscope is significant for karyotype analysis. The segmentation of image is usually achieved by a pixel-level classification task, which considers different instances as different classes. Many instance segmentation methods predict the Intersection over Union (IoU) through the head branch to correct the classification confidence. Their effectiveness is based on the correlation between branch tasks. However, none of these methods consider the correlation between input and output in branch tasks. Herein, we propose a chromosome instance segmentation network based on regression correction. First, we adopt two head branches to predict two confidences that are more related to localization accuracy and segmentation accuracy to correct the classification confidence, which reduce the omission of predicted boxes in NMS. Furthermore, a NMS algorithm is further designed to screen the target segmentation mask with the IoU of the overlapping instance, which reduces the omission of predicted masks in NMS. Moreover, given the fact that the original IoU loss function is not sensitive to the wrong segmentation, K-IoU loss function is defined to strengthen the penalty of the wrong segmentation, which rationalizes the loss of mis-segmentation and effectively prevents wrong segmentation. Finally, an ablation experiment is designed to evaluate the effectiveness of the chromosome instance segmentation network based on regression correction, which shows that our proposed method can effectively enhance the performance in automatic chromosome segmentation tasks and provide a guarantee for end-to-end karyotype analysis.

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