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1.
Antimicrob Agents Chemother ; : e0081122, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106884

RESUMO

Bedaquiline has been widely used as a part of combination dosage regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients with limited options. Although the effectiveness and safety of bedaquiline have been demonstrated in clinical trials, limited studies have investigated the significant pharmacokinetics and the impact of genotype on bedaquiline disposition. Here, we developed a population pharmacokinetic model of bedaquiline to describe the concentration-time data from Chinese adult patients diagnosed with MDR-TB. A total of 246 observations were collected from 99 subjects receiving the standard recommended dosage. Bedaquiline disposition was well described by a one-compartment model with first-order absorption. Covariate modeling identified that gamma-glutamyl transferase (GGT) and the single-nucleotide polymorphism (SNP) rs319952 in the AGBL4 gene were significantly associated with the apparent clearance of bedaquiline. The clearance (CL/F) was found to be 1.4 L/h lower for subjects with allele GG in SNP rs319952 than for subjects with alleles AG and AA and to decrease by 30% with a doubling in GGT. The model-based simulations were designed to assess the impact of GGT/SNP rs319952 on bedaquiline exposure and showed that patients with genotype GG in SNP rs319952 and GGT ranging from 10 to 50 U/L achieved the targeted maximum serum concentration at steady state (Cmax,ss). However, when GGT was increased to 100 U/L, Cmax,ss was 1.68-fold higher than the highest concentration pursued. The model developed provides the consideration of genetic polymorphism and hepatic function for bedaquiline dosage in MDR-TB adult patients.

2.
Front Immunol ; 13: 944062, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091003

RESUMO

Objective: To evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC. Methods: This open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m2, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Results: Forty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9-65.1%) and 91.3% (95% CI: 79.2-97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2-20.2 months). The median PFS was 9.0 months (95% CI: 7.1-10.9 months). The median DoR was 10.8 months (95% CI: 4.8-16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5-84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events. Conclusion: Sintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies. Clinical Trial Registration: https://ClinicalTrials.gov, identifier NCT04411706.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Capecitabina/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Estudos Prospectivos , Piridinas , Resultado do Tratamento
3.
Sci Robot ; 7(69): eabo0235, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36044556

RESUMO

Learning to combine control at the level of joint torques with longer-term goal-directed behavior is a long-standing challenge for physically embodied artificial agents. Intelligent behavior in the physical world unfolds across multiple spatial and temporal scales: Although movements are ultimately executed at the level of instantaneous muscle tensions or joint torques, they must be selected to serve goals that are defined on much longer time scales and that often involve complex interactions with the environment and other agents. Recent research has demonstrated the potential of learning-based approaches applied to the respective problems of complex movement, long-term planning, and multiagent coordination. However, their integration traditionally required the design and optimization of independent subsystems and remains challenging. In this work, we tackled the integration of motor control and long-horizon decision-making in the context of simulated humanoid football, which requires agile motor control and multiagent coordination. We optimized teams of agents to play simulated football via reinforcement learning, constraining the solution space to that of plausible movements learned using human motion capture data. They were trained to maximize several environment rewards and to imitate pretrained football-specific skills if doing so led to improved performance. The result is a team of coordinated humanoid football players that exhibit complex behavior at different scales, quantified by a range of analysis and statistics, including those used in real-world sport analytics. Our work constitutes a complete demonstration of learned integrated decision-making at multiple scales in a multiagent setting.


Assuntos
Futebol Americano , Futebol , Humanos , Aprendizagem , Movimento , Reforço Psicológico , Futebol/fisiologia
4.
Cytokine ; 158: 155979, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35914403

RESUMO

Cholestasis caused by bile secretion and excretion disorders is a serious manifestation of hepatopathy. Interleukin (IL)-25 is a member of the IL-17 cytokine family, which involves in mucosal immunity and type 2 immunity via its receptor-IL-17RB. Our previous studies have shown that IL-25 improves non-alcoholic fatty liver via stimulating M2 macrophage polarization and promotes development of hepatocellular carcinoma via alternative activation of macrophages. These hepatopathy are closely associated with cholestasis. However, whether IL-25 play an important role in cholestasis remains unclear. IL-25 treatment and IL-25 knockout (Il25-/-) mice were injected intragastrically with α-naphthyl isothiocyanate (ANIT) to determine the biological association between IL-25 and cholestasis. Here, we found that IL-25 and IL-17RB decreased in ANIT-induced cholestatic mice. Il25-/- mice showed exacerbated ANIT-induced parenchymal injury and IL-25 treatment significantly alleviated cholestatic liver injury induced by ANIT. We found that IL-25 reduced the level of hepatic total bile acids and increased the expression of multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) in liver. In conclusion, IL-25 exhibited a protective effect against ANIT-induced cholestatic liver injury in mice, which may be related to the regulation on bile acids secretion. These results provide a theoretical basis for the use of IL-25 in the treatment of cholestatic hepatopathy.


Assuntos
Colestase , Hepatopatias , 1-Naftilisotiocianato/efeitos adversos , 1-Naftilisotiocianato/metabolismo , Animais , Ácidos e Sais Biliares/farmacologia , Colestase/metabolismo , Interleucina-17/metabolismo , Fígado/metabolismo , Hepatopatias/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
5.
Iran J Public Health ; 51(4): 724-732, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35936531

RESUMO

As a result of improvements in life expectancy and reductions in fertility rate, the increasing world population ageing brings huge challenges for both developed and developing countries. Such factors as fewer children, migration of children and widowhood further increase the number of older people living alone. Older adults prefer age in place, which means care in the home. As the main place older people live in, care in community absolutely needs more attention. Optimizing health services for the elderly living in community is of positive significance to health promotion and happiness enhancement. But the traditional health service for the elderly has drawbacks of poor timeliness and high labor cost. The rapid development of modern science and technology make it possible to apply mHealth in health service for the elderly. At present, mHealth is relatively mature in the communities of developed countries. This article presents the application of mHealth in many developed countries, as references for developing countries.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35984492

RESUMO

The compounds derived from Traditional Chinese Medicines have shown various pharmacological activities with unique advantages, especially in the aspect of antitumor. Neferine (Nef), a natural compound, extracted from green seed embryos of Lotus (Nelumbo nucifera Gaertn.) also exerts antitumor effects on cancers. In this study, the effects and mechanisms of Nef on epithelial-to-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC) were evaluated. The results showed that Nef had the antitumor effects in vivo and in vitro. Nef significantly suppressed cell viability and induced apoptosis in NSCLC cells, with elevated reactive oxygen species and reduced BCL2/BAX ratio. Nef was also demonstrated to inhibit the invasion, metastasis and EMT process of NSCLC cells, and attenuate EMT-related changes of E-cadherin, N-cadherin and Vimentin at both transcriptional and translational levels. Moreover, we concluded that the inhibitory effects of Nef on EMT was achieved by targeting Rho-associated protein kinase 1, a protein mediating the process of EMT in various cancers. These results showed that Nef had a significant antitumor effect on NSCLC cells by inducing apoptosis and blocking EMT, providing the therapeutical prospect on NSCLC treatment.

7.
Front Neurol ; 13: 954509, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968289

RESUMO

Background: Traumatic brain injury (TBI) has been recognized as an important and common cause of epilepsy since antiquity. Posttraumatic epilepsy (PTE) is usually associated with drug resistance and poor surgical outcomes, thereby increasing the burden of the illness on patients and their families. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy. This study aimed to determine the efficacy of VNS for refractory PTE and to initially evaluate the potential predictors of efficacy. Methods: We retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PTE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (≥50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS efficacy. Results: In total, forty-five patients with refractory PTE who underwent VNS therapy were enrolled. Responders were found in 64.4% of patients, and 15.6% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 37.8, 44.4, 60, and 67.6% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, generalized interictal epileptic discharges (IEDs) were found to be a negative predictor (OR: 4.861, 95% CI: 1.145-20.632) of VNS efficacy. Conclusion: The results indicated that VNS therapy was effective in refractory PTE patients and was well tolerated over a 1-year follow-up period. Patients with focal or multifocal IEDs were recognized to have better efficacy after VNS therapy.

8.
BMC Pulm Med ; 22(1): 309, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962350

RESUMO

BACKGROUND: Tuberculosis (TB) is one of the main infectious diseases that seriously threatens global health, while diagnostic delay (DD) and treatment dramatically threaten TB control. METHODS: Between 2005 and 2017 in Shandong, China, we enrolled pulmonary tuberculosis (PTB) patients with DD. DD trends were evaluated by Joinpoint regression, and associations between PTB patient characteristics and DD were estimated by univariate and multivariate logistic regression. The influence of DD duration on prognosis and sputum smear results were assessed by Spearman correlation coefficients. RESULTS: We identified 208,822 PTB cases with a median DD of 33 days (interquartile range (IQR) 18-63). The trend of PTB with DD declined significantly between 2009 and 2017 (annual percent change (APC): - 4.0%, P = 0.047, 2009-2013; APC: - 6.6%, P = 0.001, 2013-2017). Patients aged > 45 years old (adjusted odds ratio (aOR): 1.223, 95% confidence interval (CI) 1.189-1.257, 46-65 years; aOR: 1.306, 95% CI 1.267-1.346, > 65 years), farmers (aOR: 1.520, 95% CI 1.447-1.596), and those with a previous treatment history (aOR: 1.759, 95% CI 1.699-1.821) were prone to developing long DD (> 30 days, P < 0.05). An unfavorable outcome was negatively associated with a short DD (OR: 0.876, 95% CI 0.843-0.910, P < 0.001). Sputum smear positive rate and unfavorable outcomes were positively correlated with DD duration (Spearman correlation coefficients (rs) = 1, P < 0.001). CONCLUSIONS: The DD situation remains serious; more efficient and comprehensive strategies are urgently required to minimize DD, especially for high-risk patients.


Assuntos
Tuberculose Pulmonar , Tuberculose , China/epidemiologia , Diagnóstico Tardio , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tuberculose/diagnóstico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia
9.
Orthod Craniofac Res ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-36004578

RESUMO

OBJECTIVE: The objective of the study was to explore and validate the consensus of orthodontic experts on the assessment of orthodontic treatment outcomes based on subjective and objective analysis. MATERIALS AND METHODS: The research consisted of two parts: the exploration and verification of expert consensus. First, a sample of 108 cases randomly selected from six dental schools in China were evaluated by 69 orthodontic experts and measured by researchers based on post-treatment study casts and lateral cephalograms, respectively. Then, through statistical analysis, the objective indicators significantly correlated with experts' subjective evaluations were selected, their weights were determined, and the critical values of satisfactory, acceptable and unacceptable grades were screened. Subsequently, another sample of 72 cases were evaluated by another 36 orthodontic experts, and the subjective evaluation results were compared with the objective measurement results. RESULTS: There were six model indicators and seven cephalometric indicators being significantly correlated with the experts' subjective evaluations, including occlusal contact, overjet, midline, interproximal contact, alignment, occlusal relationship, L1/NB, ANB, SN/OP, U1/SN, LL-EP, Cm-Sn-UL and Ns-Prn-Pos, with a cumulative R2 of 0.704. In the verification part, the correlation coefficient between the 36 experts' subjective scores and objective regression scores was 0.716 (P < .001); the correlation coefficient between the 36 experts' subjective grades and objective grades was 0.757 (P < .001). CONCLUSIONS: Orthodontic experts had good consistency in the subjective evaluation of the combined records of post-treatment study casts and lateral cephalograms. The objective indicators selected from subjective and objective analysis had good reliability and validity and could further improve the existing occlusal indices.

10.
Clin Transl Med ; 12(8): e945, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35979619

RESUMO

BACKGROUND: Recently, the mechanism by which cells adapt to intrinsic and extrinsic stresses has received considerable attention. Tat-interactive protein 60-kDa/ataxia-telangiectasia-mutated (TIP60/ATM) axis-mediated DNA damage response (DDR) is vital for maintaining genomic integrity. METHODS: Protein levels were detected by western blot, protein colocalisation was examined by immunofluorescence (IF) and protein interactions were measured by co-immunoprecipitation, proximity ligation assay and GST pull-down assays. Flow cytometry, comet assay and IF assays were used to explore the biological functions of sequence similarity 135 family member B (FAM135B) in DDR. Xenograft tumour, FAM135B transgenic mouse models and immunohistochemistry were utilised to confirm in vitro observations. RESULTS: We identified a novel DDR regulator FAM135B which could protect cancer cells from genotoxic stress in vitro and in vivo. The overexpression of FAM135B promoted the removal of γH2AX and 53BP1 foci, whereas the elimination of FAM135B attenuated these effects. Consistently, our findings revealed that FAM135B could promote homologous recombination and non-homologous end-joining repairs. Further study demonstrated that FAM135B physically bound to the chromodomain of TIP60 and improved its histone acetyltransferase activity. Moreover, FAM135B enhanced the interactions between TIP60 and ATM under resting conditions. Intriguingly, the protein levels of FAM135B dramatically decreased following DNA damage stress but gradually increased during the DNA repair period. Thus, we proposed a potential DDR mechanism where FAM135B sustains a reservoir of pre-existing TIP60-ATM assemblies under resting conditions. Once cancer cells suffer DNA damage, FAM135B is released from TIP60, and the functioning pre-assembled TIP60-ATM complex participates in DDR. CONCLUSIONS: We characterised FAM135B as a novel DDR regulator and further elucidated the role of the TIP60-ATM axis in response to DNA damage, which suggests that targeting FAM135B in combination with radiation therapy or chemotherapy could be a potentially effective approach for cancer treatment.


Assuntos
Dano ao DNA , Reparo do DNA , Acetilação , Animais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Dano ao DNA/genética , Reparo do DNA/genética , Humanos , Camundongos , Processamento de Proteína Pós-Traducional
11.
Nutrients ; 14(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35889766

RESUMO

Thymol is a natural antibacterial agent found in the essential oil extracted from thyme, which has been proven to be beneficial in food and medicine. Meanwhile, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and autophagy have been reported to play key roles in the progression of liver injury. However, the effects of thymol on the NLRP3 inflammasome and autophagy in protecting the liver remain unclear. The present study used a mouse model with liver injury induced by lipopolysaccharides (LPS) to investigate the regulatory mechanisms of thymol. We found that thymol alleviated LPS-induced liver structural damage, as judged by reduced inflammatory cell infiltration and improved structure. In addition, elevated levels of the liver damage indicators (alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (TBIL)) dropped after thymol administration. The mRNA and protein expression of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-22), apoptosis-related genes (caspase3 and caspase9), and the activity of apoptosis-related genes (caspase3 and caspase9) were increased in LPS-treated livers, whereas the changes were alleviated after thymol administration. Thymol inhibited LPS-induced increment in lactate dehydrogenase (LDH) activity in primary hepatocytes of the mouse. In addition, thymol protected mice from liver injury by inhibiting NLRP3 inflammasome activation induced by LPS. Mechanistically, the present study indicates that thymol has liver protective activity resulting from the modulation of the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) to regulate the autophagy pathway, hence curbing inflammation.


Assuntos
Hepatite , Timol , Proteínas Quinases Ativadas por AMP , Animais , Apoptose , Autofagia , Hepatite/tratamento farmacológico , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Serina-Treonina Quinases TOR , Timol/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
12.
Curr Neuropharmacol ; 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794774

RESUMO

Epilepsy and autism spectrum disorder (ASD) are highly mutually comorbid, suggesting potential overlaps in genetic etiology, pathophysiology, and neurodevelopmental abnormalities. Adenosine, an endogenous anticonvulsant and neuroprotective neuromodulator of the brain, has been proved to affect the process of epilepsy and ASD. On the one hand, adenosine plays a crucial role in preventing the progression and development of epilepsy through adenosine receptor-dependent and -independent ways. On the other hand, adenosine signaling can not only regulate core symptoms but also improve comorbid disorders in ASD. Given the important role of adenosine in epilepsy and ASD together, therapeutic strategies related to adenosine, including the ketogenic diet, neuro-modulation therapy, and adenosine augmentation therapy, have been suggested for the arrangement of epilepsy and ASD. There are several proposals in this review. Firstly, based on the comorbid symptoms and mechanisms of epilepsy and ASD, to further discuss the relationship between both diseases. Secondly, to explore the role of adenosine involved in epilepsy and ASD. Lastly, to emphasize the potential therapeutic value and clinical approaches of adenosine-related therapies in treating epilepsy and ASD.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35815260

RESUMO

Cisplatin, also known as cis-diamine dichloroplatinum (CDDP), is a widely used chemotherapeutic drug. However, its application is limited by the occurrence of serious nephrotoxicity. Currently, no effective therapy is available for combating CDDP-induced acute kidney injury (AKI). In the present study, we investigated the efficacy of Jianpi Yishen Tang (JPYST), a traditional Chinese medicine (TCM) compound commonly used to treat chronic kidney disease, against CDDP-induced AKI. In the CDDP + JPYST group, male mice were pretreated with JPYST (18.35 g/kg/day) for 5 consecutive days before receiving a single dose of CDDP (20 mg/kg), all mice were sacrificed 72 h after the CDDP injection. Results showed that JPYST suppressed CDDP-induced kidney dysfunction and tubular damage scores in the mice. Mechanistically, JPYST treatment attenuated CDDP-induced renal tubular cell apoptosis in AKI mice, as manifested by a marked decreased in TUNEL-positive cell counts, downregulation of the pro-apoptotic proteins Bax, Bad and caspase 3, and upregulation of the antiapoptotic protein Bcl-2 in kidney tissues. Meanwhile, JPYST decreased the expression of inflammatory cytokines TNF-α, IL-1ß, and IL-6 in the serum and renal tissues of mice following CDDP administration. These factors are involved in suppressing the activation of phospho-NF-κB p65 in tubular epithelial cells. Taken together, these findings demonstrated that JPYST exerts renoprotective effects against CDDP-induced AKI through antiapoptosis and anti-inflammation effects, and these are associated with downregulation of NF-κB activation. Therefore, JPYST has potential for development of treatment therapies against CDDP-induced AKI.

14.
Medicine (Baltimore) ; 101(26): e29798, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35776993

RESUMO

Lymphovascular invasion is considered to be a high-risk pathological feature after radical resection of gastric cancer, but the relationship between lymphovascular invasion and the prognosis of stage I gastric cancer is still controversial. Therefore, we used meta-analysis to systematically evaluate the relationship between lymphovascular invasion and the prognosis of stage I gastric cancer. Up to September 2, 2021, the databases of PubMed, EMBASE, Cochrane Library, CNKI, and Wanfang were searched. According to the inclusion and exclusion criteria, 2 researchers independently completed the screening of literature, extraction of data, and quality evaluation. Meta-analysis was performed using RevMan 5.4 software merged with HR and 95%CI. A total of 7508 patients with stage I gastric cancer were included in 9 studies, and the positive rate of lymphovascular invasion was 17%. Lymphovascular invasion was significantly associated with shorter overall survival (OS) (univariate: HR = 4.05, 95%CI: 1.91-8.58; multivariate: HR = 2.10, 95%CI: 1.37-3.22) and relapse-free survival (RFS) (univariate: HR = 4.79, 95%CI: 2.30-9.99; multiple: HR = 2.17, 95%CI: 1.56-3.00). This study indicates that lymphovascular invasion is an independent risk factor affecting the prognosis of patients with stage I gastric cancer, and can be used as a reference index for postoperative adjuvant therapy.


Assuntos
Neoplasias Gástricas , Humanos , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/patologia
15.
Scand J Gastroenterol ; : 1-8, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35793450

RESUMO

OBJECTIVE: To determine the risk factors for emergency endoscopic variceal ligation (EVL) failure in acute variceal bleeding (AVB). METHODS: Data from 161 cirrhosis patients with oesophageal variceal bleeding who underwent emergency EVL treatment at the Second Hospital of Hebei Medical University from January 2018 to May 2021 were retrospectively analysed. Enrolled patients were divided into a successful treatment group and a failed treatment group. The variables studied were demographic, clinical, imaging, laboratory, and endoscopic data from the enrolled patients. RESULTS: Of the enrolled patients, 19 patients experienced emergency EVL failure. Of these patients, nine underwent emergency endoscopic treatment again, six patients were treated with a Sengstaken-Blakemore tube for haemostasis and endoscopic treatment, four patients received drug therapy. The presence of portal vein thrombosis (PVT) in the failure group was higher than that in the success group (p < .05). Active bleeding on endoscopy was associated with emergency EVL failure for patients with Child-Pugh class C (p < .05). CONCLUSIONS: Child-Pugh class C with active bleeding on endoscopy or the presence of PVT could increase the risk of emergency EVL failure. The patient's condition should be fully evaluated before emergency endoscopic treatment to reduce the risk of failure.

16.
Chemosphere ; 307(Pt 2): 135664, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35850228

RESUMO

This study compared effects of conventional ozonation and electrochemical oxidation (EO) on the formation of aldehydes and aliphatic carboxylic acids produced via the oxidation of natural organic matter (NOM) present in a low-mineralized surface water with a relatively low NOM concentration. Conventional ozonation and EO were effective in degrading the aromatic moiety of NOM characterized by the absorbance at 254 nm. Yields of aliphatic carboxylic acids in the ozone treated water were dominated by formate, acetate and oxalate, while no acetate was observed in the case of EO treatment. The speciation of aldehydes was similar in the case of ozonation and EO treatment, but the aldehydes yields were notably higher for ozonation. The presence of the elevated carbonate concentration moderated the changes in disinfection by-products (DBPs) concentration in the EO treated water due to the interception of ∙OH by HCO3-, while it did not affect ozonation treatment. This study allows gaining more insights into the nature of processes characteristic and optimization of disinfections based on ozonation and EO methods.

17.
BMJ Open ; 12(7): e059316, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35851012

RESUMO

OBJECTIVES: To estimate anaemia prevalence and the associated factors among hospitalised people living with HIV (PLHIV) receiving antiretroviral therapy (ART). DESIGN: A cross-sectional study. SETTING: PLHIV receiving ART and hospitalised in a specialised hospital for infectious disease in Guizhou Province, Southwest China, between 1 January 2018 and 31 March 2021. PARTICIPANTS: A total of 6959 hospitalised PLHIV aged ≥18 years and receiving ART were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Anaemia was diagnosed as a haemoglobin concentration <120 g/L for non-pregnant females and <130 g/L for males. Mild, moderate and severe anaemia were diagnosed as below the gender-specific lower limit of normal but ≥110 g/L, 80-110 g/L and <80 g/L, respectively. RESULTS: The prevalence of anaemia was 27.5%, and that of mild, moderate and severe anaemia was 9.2%, 12.2% and 6.1%, respectively. Results from multivariate logistic regression showed that females had increased odds of anaemia (adjusted OR (aOR)=1.60, 95% CI: 1.42 to 1.81) compared with males. Widowed or divorced inpatients (anaemia: aOR=1.26, 95% CI: 1.08 to 1.47; severe anaemia: aOR=1.52, 95% CI: 1.16 to 1.97) and thrombocytopenia inpatients (anaemia: aOR=4.25, 95% CI: 3.54 to 5.10; severe anaemia: aOR=4.16, 95% CI: 3.24 to 5.35) had increased odds of anaemia and severe anaemia compared with their counterparts. Hepatitis C was associated with increased odds of severe anaemia (aOR=1.80, 95% CI: 1.11 to 2.92). CONCLUSIONS: Anaemia was prevalent among hospitalised PLHIV. Female sex, those widowed or divorced, and thrombocytopenia were associated with increased odds of anaemia, and those widowed or divorced, thrombocytopenia and hepatitis C were associated with increased odds of severe anaemia. Determination of anaemia predictors, early detection and timely management of anaemia are crucial to prevent anaemia progression.


Assuntos
Anemia , Infecções por HIV , Hepatite C , Trombocitopenia , Adolescente , Adulto , Anemia/complicações , Anemia/etiologia , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C/complicações , Humanos , Masculino , Prevalência , Fatores de Risco
18.
BMJ Open ; 12(7): e059149, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902191

RESUMO

OBJECTIVES: To investigate the independent and collective impact of alcohol drinking and tobacco smoking on the drug-resistance of newly diagnosed tuberculosis (TB). DESIGN: This was a retrospective cohort study. SETTING: Shandong, China. PARTICIPANTS: Patients with newly diagnosed TB from 1 January 2004 to 31 December 2020 were collected. Exclusive criteria: retreated cases; extrapulmonary tuberculosis; without information on drug susceptibility testing results, smoking or drinking habits; bacteriological identification as non-tuberculous mycobacteria. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients were classified into four groups including smokers only (G1), drinker only (G2), smoker +drinker (G3), non-smoker +non-drinker group (G0). We described the drug-resistant profiles, clinical factors and calculated the ORs of different drug-resistance among G1, G2, G3, compared with G0 through univariate and multivariate logistics regression models. RESULTS: Of the 7996 TB cases enrolled, the proportions of G1, G2, G3 and G0 were 8.25%, 3.89%, 16.46% and 71.40%, respectively. The rates of drug-resistant (DR)-TB, mono-resistant TB, multidrug resistant (MDR)-TB, polydrug resistant TB in G1, G2, G3 and G0 were 19.24%/16.4%/17.33%/19.08%, 11.52%/8.68%/10.94%/11.63%, 3.03%/2.57%/2.96%/3.66% and 4.70%/4.82%/3.34%/ 4.08%, respectively. G3 had a higher risk of MDR1: isoniazid +rifampin (adjusted OR (aOR)=1.91, 95% CI: 1.036 to 3.532), but had a lower risk of DR-TB (aOR=0.84, 95% CI: 0.71 to 0.99), rifampin-related resistance (aOR=0.68, 95% CI: 0.49 to 0.93), streptomycin-related resistance (aOR=0.82, 95% CI: 0.68 to 0.99), ethambutol-related resistance (aOR=0.57, 95% CI: 0.34 to 0.95), MDR3: isoniazid +rifampin+streptomycin (aOR=0.41, 95% CI: 0.19 to 0.85), any isoniazid +streptomycin resistance (aOR=0.85, 95% CI: 0.71 to 1.00). However, there were no significant differences between G1 and G0, G2 and G0 in all drug-resistant subtypes. Those patients with cavity had a higher risk of DR-TB among G3 (OR=1.35, 95% CI: 1.01 to 1.81). CONCLUSION: Although we did not found an independent impact of alcohol drinking or tobacco smoking on TB drug-resistance, respectively, these two habits had a combined effect on TB drug-resistance.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Consumo de Bebidas Alcoólicas/epidemiologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , China/epidemiologia , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Modelos Logísticos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Rifampina/farmacologia , Rifampina/uso terapêutico , Estreptomicina/farmacologia , Estreptomicina/uso terapêutico , Fumar Tabaco , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
19.
J Am Heart Assoc ; 11(13): e023868, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35730646

RESUMO

Background Histidyl dipeptides such as carnosine are present in a micromolar to millimolar range in mammalian hearts. These dipeptides facilitate glycolysis by proton buffering. They form conjugates with reactive aldehydes, such as acrolein, and attenuate myocardial ischemia-reperfusion injury. Although these dipeptides exhibit multifunctional properties, a composite understanding of their role in the myocardium is lacking. Methods and Results To identify histidyl dipeptide-mediated responses in the heart, we used an integrated triomics approach, which involved genome-wide RNA sequencing, global proteomics, and unbiased metabolomics to identify the effects of cardiospecific transgenic overexpression of the carnosine synthesizing enzyme, carnosine synthase (Carns), in mice. Our result showed that higher myocardial levels of histidyl dipeptides were associated with extensive changes in the levels of several microRNAs, which target the expression of contractile proteins, ß-fatty acid oxidation, and citric acid cycle (TCA) enzymes. Global proteomic analysis showed enrichment in the expression of contractile proteins, enzymes of ß-fatty acid oxidation, and the TCA in the Carns transgenic heart. Under aerobic conditions, the Carns transgenic hearts had lower levels of short- and long-chain fatty acids as well as the TCA intermediate-succinic acid; whereas, under ischemic conditions, the accumulation of fatty acids and TCA intermediates was significantly attenuated. Integration of multiple data sets suggested that ß-fatty acid oxidation and TCA pathways exhibit correlative changes in the Carns transgenic hearts at all 3 levels. Conclusions Taken together, these findings reveal a central role of histidyl dipeptides in coordinated regulation of myocardial structure, function, and energetics.


Assuntos
Carnosina , Dipeptídeos , Animais , Carnosina/farmacologia , Proteínas Contráteis/metabolismo , Dipeptídeos/química , Dipeptídeos/metabolismo , Dipeptídeos/farmacologia , Ácidos Graxos/metabolismo , Mamíferos/metabolismo , Camundongos , Miocárdio/metabolismo , Oxirredução , Proteômica
20.
Chemphyschem ; 23(18): e202200219, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-35676199

RESUMO

Ionic liquid mixed with poly(methyl methacrylate)-grafted Fe3 O4 nanoparticle aggregates at low particle concentrations was found to exhibit different dynamics and ionic conductivity than that of pure ionic liquid in our previous studies. In this work, we report on the quasi-elastic neutron scattering results of ionic liquid containing polymer-grafted Fe3 O4 nanoparticles at higher particle concentrations. The diffusivity of imidazolium (HMIM+ ) cations of 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (HMIM-TFSI) in the presence of poly(methyl methacrylate)-grafted Fe3 O4 nanoparticles is discussed through the confinement. Analysis of the elastic incoherent structure factor revealed that the confinement radius decreased with the addition of grafted particles in HMIM-TFSI/solvent mixture. We propose the confinement that is induced by the high concentration of grafted particles shrinks the HMIM-TFSI restricted volume. We further conjecture that this enhanced diffusivity occurs as a result of the local ordering of cations within aggregates of poly(methyl methacrylate)-grafted Fe3 O4 nanoparticles.


Assuntos
Líquidos Iônicos , Nanopartículas , Cátions , Imidas/química , Líquidos Iônicos/química , Polímeros/química , Polimetil Metacrilato
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