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1.
Medicine (Baltimore) ; 100(5): e24065, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592859

RESUMO

BACKGROUND: This systematic review and meta-analysis was performed to evaluate the clinical efficacy and safety of traditional Chinese manipulation in treating ankle sprains. METHODS: Seven databases were searched from inception to July 2020. A meta-analysis of randomized controlled trials comparing traditional Chinese manipulation and other conservative therapy for ankle sprains was conducted. The Cochrane Handbook tool was applied to access the quality and risk of bias of each study. The meta-analysis was performed with Review Manager 5.3 software (Nordic Cochrane Centre, Copenhagen, Denmark). RESULTS: In total, 14 articles and 1112 patients were included. The total effective rate of ankle manipulation was much higher than that of other conservative therapy (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.17-1.30; P < .00001). The Baird-Jackson score (RR, 10.14; 95% CI, 5.57-14.70; P < .0001), visual analog scale score (RR, -1.78; 95% CI, -3.14 to -0.43; P = .01), and American Orthopaedic Foot and Ankle Society ankle-hindfoot score (RR, 15.70; 95% CI, 12.72-18.68; P < .00001) were significantly lower in the manipulation group than in the control group. Further subgroup analysis showed that the visual analog scale score of the rotating-traction-poking manipulation was significantly lower than that of the control group (RRRTPM, -2.56; 95% CI, -4.54 to -0.58; P = .01), while there were no significant differences between the effects of other manipulations and the control group (RRother manipulation, -0.62; 95% CI, -1.52 to 0.28; P = .18). CONCLUSION: Traditional Chinese manipulation might have a better effect on ankle sprains than other types of conservative treatment. The rotating-traction-poking manipulation might achieve better effects than other manipulation techniques in terms of alleviating pain intensity. However, considering the overall high or unclear risk of bias, the evidence identified does not allow for a robust conclusion concerning the efficacy and safety of traditional Chinese manipulation for treating ankle sprains. High-quality randomized controlled trials are needed to confirm these findings.


Assuntos
Traumatismos do Tornozelo/terapia , Manipulação Ortopédica/métodos , Medicina Tradicional Chinesa/métodos , Humanos , Resultado do Tratamento
2.
Molecules ; 26(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573254

RESUMO

S100B(ßß) proteins are a family of multifunctional proteins that are present in several tissues and regulate a wide variety of cellular processes. Their altered expression levels have been associated with several human diseases, such as cancer, inflammatory disorders and neurodegenerative conditions, and hence are of interest as a therapeutic target and a biomarker. Small molecule inhibitors of S100B(ßß) have achieved limited success. Guided by the wealth of available experimental structures of S100B(ßß) in complex with diverse peptides from various protein interacting partners, we combine comparative structural analysis and molecular dynamics simulations to design a series of peptides and their analogues (stapled) as S100B(ßß) binders. The stapled peptides were subject to in silico mutagenesis experiments, resulting in optimized analogues that are predicted to bind to S100B(ßß) with high affinity, and were also modified with imaging agents to serve as diagnostic tools. These stapled peptides can serve as theranostics, which can be used to not only diagnose the levels of S100B(ßß) but also to disrupt the interactions of S100B(ßß) with partner proteins which drive disease progression, thus serving as novel therapeutics.

3.
Plant J ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595139

RESUMO

Elucidating the biochemical and molecular basis of premature abscission in fruit crops should help develop strategies to enhance fruit set and yield. Here, we report that LcERF2 contributes to differential abscission rates and responses to ethylene in Litchi chinensis. Reduced LcERF2 expression in litchi was observed to reduce fruit abscission, concurrent with enhanced pedicel growth with increased levels of hexoses, particularly galactose, as well as the pectin abundance in cell wall. Ecoptic expression of LcERF2 in Arabidopsis thaliana caused enhanced petal abscission, together with retarded plant growth and reduced pedicel galactose and pectin contents. Transcriptome analysis indicated that LcERF2 modulates the expression of genes involved in cell wall modification. Yeast one-hybrid, dual-luciferase reporter, and electrophoretic mobility shift assays all demonstrated that a UDP-glucose 4-epimerase gene (LcUGE) was the direct downstream target of LcERF2. This result was further supported by a significant reduction in expression of the A. thaliana homolog, AtUGE2-4, in response to LcERF2 over-expression. Significantly reduced pedicel diameter and enhanced litchi fruit abscission were observed in response to the LcUGE silencing. We conclude that LcERF2 mediates fruit abscission by orchestrating cell wall metabolism and thus pedicel growth, in part by repressing the expression of LcUGE.

4.
Shock ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33595259

RESUMO

OBJECTIVE: To compare the efficacy of four therapeutic methods to modify gut microbiota dysbiosis and brain dysfunction in septic rats. METHODS: Rats were treated with fecal microbiota transplantation, prebiotics, probiotics, and synbiotics after exposure to lipopolysaccharide. The diversity and composition of gut microbiota, electroencephalogram values, and the concentrations of TNF-α, IL-1ß, and IL-6 in the cortex were analyzed. RESULTS: Fecal microbiota transplantation was the most efficacious method to restore intestinal microbial diversity and exert the best corrective effects in modulating microbial composition in septic rats. More interestingly, fecal microbiota transplantation exerted the best protective effects in brain dysfunction in septic rats. CONCLUSION: Among the four methods, fecal microbiota transplantation was the most useful method to modify the dysbiosis of intestinal microbiota and improve brain function in septic rats. These findings reveal the protective consequence of microbiota modification, and the findings suggest opportunities to improve brain function in sepsis.

5.
Adv Mater ; 33(8): e2001588, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33470483

RESUMO

Lignin serves as a binder that forms strong matrices of the cell walls of wood. However, it has many photolabile chromophore groups that create a monotonic brownish color and make wood susceptible to photodegradation. Herein, a new strategy is reported for modifying lignin using an in situ, rapid, and scalable process that involves the photocatalytic oxidation of native lignin in wood by H2 O2 and UV light. The reaction selectively eliminates lignin's chromophores while leaving the aromatic skeleton intact, thus modulating the optical properties of wood. The resulting "photonic wood" retains ≈80% of its original lignin content, which continues to serve as a strong binder and water-proofing agent. As a result, photonic wood features a much higher mechanical strength in a wet environment (20-times higher tensile strength and 12-times greater compression resistance), significant scalability (≈2 m long sample), and largely reduced processing times (1-6.5 h vs 4-14 h) compared with delignification methods. Additionally, this in situ lignin-modified wood structure is easily patterned through a photocatalytic oxidation process. This photocatalytic production of photonic wood paves the way for the large-scale manufacturing of sustainable biosourced functional materials for a range of applications, including energy-efficient buildings, optical management, and fluidic, ionic, electronic, and optical devices.

6.
Mediators Inflamm ; 2021: 5318369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505213

RESUMO

Acute kidney injury (AKI) is a common organ injury in sepsis, which leads to poor prognosis. Long noncoding RNA (lncRNA) small nucleolus RNA host gene 14 (SNHG14) was recognized to induce cell injury in LPS-induced acute lung injury and Parkinson's disease. We want to investigate the functions and mechanisms of SNHG14 in sepsis-induced AKI. Increased expression of SNHG14 was observed in LPS-induced HK-2 cells, and this was due to the activation of the TLR4/NF-κB pathway. In vitro studies showed that SNHG14 was involved in the oxidative stress, inflammation, and apoptosis of LPS-induced HK-2 cells. Further investigations confirmed that SNHG14 exerted the functions via miR-93 which could regulate the activation of NF-κB and STAT3 signaling by targeting IRAK4 and IL-6R. We also found that silencing SNHG14 also alleviated cellular injury processes of IL-1ß and IL-6 in HK-2 cells via miR-93. We demonstrate that SNHG14 accelerates cellular injury in sepsis-induced AKI by activating IRAK4/NF-κB and IL-6R/STAT3 signaling via miR-93.

7.
J Viral Hepat ; 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33423348

RESUMO

Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p = 0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p = 0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0, 13.0) vs. 15.0 (IQR -3.0, 21.0) vs. 5.0 (IQR -9.0, 14.0), respectively (p = 0.334), while the median changes of eGFR were -2.12 (IQR -13.87, 1.44) vs. -10.43 (IQR -20.21, 3.18) vs. -5.31 (IQR -14.72, 5.44) ml/min/1.73 m2 , respectively (p = 0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.

8.
Crit Care ; 25(1): 8, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402210

RESUMO

BACKGROUND: Burnout has gained increasing attention worldwide; however, there is a lack of relevant research in China. This study investigated the prevalence and factors associated with burnout in physicians of the intensive care unit (ICU) in mainland China. METHODS: This cross-sectional multicenter study included critical care physicians from all provinces in mainland China (except Tibet). A self-administered survey questionnaire was conducted. It included three parts: demographic information, lifestyle and work information, and the Maslach Burnout Inventory. The levels of burnout were calculated. The factors independently associated with burnout were analyzed by logistic regression. RESULTS: Finally, 1813 intensivists participated in the survey. The participation rate was 90.7%. The prevalence of burnout and severe burnout was 82.1% (1489/1813) and 38.8% (704/1813), respectively. According to the logistic regression analysis, "difficulty in making treatment decisions" was independently associated with burnout [OR = 1.365, CI (1.060, 1.757)]. "Higher number of children" [OR = 0.714, CI (0.519, 0.981)] and higher "income satisfaction" [OR = 0.771, CI (0.619, 0.959)] were independent protective factors against severe burnout. CONCLUSIONS: The burnout rate in ICU physicians in China is high. Difficult treatment decisions, the number of children, and income satisfaction are independently associated with burnout rates among ICU physicians in China. TRIAL REGISTRATION: Burnout syndrome of the Chinese personnel working in intensive care units: a survey in China, ChiCTR-EOC-17013044, registered October 19, 2017. http://www.chictr.org.cn/showproj.aspx?proj=22329 .

9.
Pediatr Rheumatol Online J ; 19(1): 2, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407602

RESUMO

BACKGROUND: To summarize the characteristics of gastrointestinal (GI) perforation in anti-nuclear matrix protein 2 (NXP2) antibody-associated juvenile dermatomyositis (JDM). METHODS: Five patients with GI perforation from a JDM cohort of 120 cases are described. Relevant literature was reviewed. RESULTS: Five patients, including four females and one male, were included in the study. The age of onset of these patients ranged from 3.3 to 9.5 years with the median age of 5.0 years. When these patients were complicated by GI perforation, childhood myositis assessment score (CMAS) ranged from 1 to 5 with the median score of 2. Myositis-specific antibody (MSA) spectrum analysis indicated that the five patients were anti-NXP2 antibody positive. The initial symptoms of GI perforation were progressive abdominal pain and intermittent fever. Two patients also presented with ureteral calculus with hydronephrosis and ureteral stricture. Surgery was performed in four patients. One patient failed to undergo a repair as the perforation was high in position. For the other three patients, perforation repair was successful, of which two patients failed due to recurrent perforation. At 24 months postoperative follow-up, one patient was in complete remission on prednisone (Pred) and methotrexate (MTX) treatment, and her ureteral stricture had disappeared. The other four patients died. Adding these cases with 16 other patients described in the literature, the symptom at onset was progressive abdominal pain, which often occurred within 10 months after JDM was diagnosed. Perforation most commonly occurred in the duodenum, although it also occurred at multiple sites or was recurrent. The mortality rate of GI perforation in JDM was 38% (8/21). CONCLUSIONS: All the five perforation cases in our study subjected to MSA analysis were anti-NXP2 antibody positive. The symptom at onset was abdominal pain. The most common site of perforation was the duodenum in the retroperitoneum, and the lack of acute abdominal manifestations prevented early diagnosis. GI perforation may be a fatal complication in JDM, and early diagnosis is very important. More research is needed to determine the pathogenesis and predictive factors of GI perforation in JDM.

10.
Pediatr Rheumatol Online J ; 19(1): 6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407621

RESUMO

BACKGROUND: Juvenile dermatomyositis (JDM) is a rare and sometimes fatal disease in children. The anti-NXP2 antibody is one of the most common antibodies and muscle ischaemia associated with NXP2 autoantibodies was a severe subtype of JDM. Further information is needed regarding clinical characteristics and factors associated with poor prognosis. But there are no reports about clinical characteristics and high risk factor of poor prognosis. For the first time, we introduced the clinical characteristics and poor predictors of anti-NXP2 antibody-associated juvenile dermatomyositis in Chinese children. METHODS: Twenty-six patients with anti-NXP2 antibody-related JDM from 85 JDM Chinese patients were diagnosed from January 2016 to November 2019. Logistic regression was used to analyze the risk factors for refractory cases and mortality. RESULTS: The ratio of male to female was 1:1.9. The median age of onset was 4.5 (1-13) years. Twenty-four cases (92.3%) had rash and muscle weakness. Treatments included glucocorticoids, immunosuppressive agents, biological agents (7 cases), plasma exchange, Janus kinase inhibitor (7 cases) and autologous stem cell transplant (1 case). Refractory JDM patients (11/26, 42.3%) were associated with edema, skin ulcer, muscle strength<=grade 3, CD4/CD8 ratio < 1.4 and ferritin > 200µg/ml. Among 6 cases (6/26, 23.1%) with severe gastrointestinal involvement, 5 cases died and 1 case survived after autologous stem cell transplant (ASCT). The risk factors for gastrointestinal involvement and mortality were edema, skin ulcer, severe muscle weakness (dysphagia/ hoarseness/ soft voice), BMI < 15 and ANA positive. CONCLUSIONS: Edema, skin ulcer and severe muscle weakness predicted refractory disease, GI involvement, and mortality in anti-NXP2 antibody-positive JDM of Chinese children. Decreased CD4/CD8 ratio and high ferritin related with refractory cases, and very low BMI and ANA (+) are probably, associated with gastrointestinal involvement and mortality. TRIAL REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=49846 .

11.
Talanta ; 223(Pt 1): 121687, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303140

RESUMO

In this work, an electrochemiluminescence resonance energy transfer (ECL-RET) system was established based on the modified graphite phase carbon nitride to detect brombuterol residues in food. The ultrasonic-assisted acidification exfoliation modification improved the conductivity and specific surface area of the graphite phase carbon nitride (g-C3N4). In addition, the carboxylated g-C3N4 nanosheets as ECL donors and the Au-Ag alloy nanoparticles as ECL acceptors could respectively directly carry antigen and antibody. Therefore, the trouble of introducing additional bridge molecules was avoided. A competitive immunoassay strategy was used for the detection of brombuterol, where brombuterol in the sample would compete with the coating antigen for the limited binding sites on antibody. The proposed ECL immunosensor for brombuterol detection exhibited high sensitivity with a wide linear range from 0.001 ng mL-1 to 1000 ng mL-1 and a low detection limit at 0.31 pg mL-1. This work adopts a very simple way to design the sensor without losing its sensitivity, bringing convenience to its possible future applications.

12.
J Dairy Sci ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33272580

RESUMO

This study was conducted to examine the effect of active dry yeast (ADY) supplementation on lactation performance, ruminal fermentation patterns, and CH4 emissions and to determine an optimal ADY dose. Sixty Holstein dairy cows in early lactation (52 ± 1.2 DIM) were used in a randomized complete design. Cows were blocked by parity (2.1 ± 0.2), milk production (35 ± 4.6 kg/d), and body weight (642 ± 53 kg) and assigned to 1 of 4 treatments. Cows were fed ADY at doses of 0, 10, 20, or 30 g/d per head for 91 d, with 84 d for adaptation and 7 d for sampling. Although dry matter intake was not affected by ADY supplementation, the yield of actual milk, 4% fat-corrected milk, milk fat yield, and feed efficiency increased quadratically with increasing ADY supplementation. Yields of milk protein and lactose increased linearly with increasing ADY doses, whereas milk urea nitrogen concentration and somatic cell count decreased quadratically. Ruminal pH and ammonia concentration were not affected by ADY supplementation, whereas ruminal concentration of total volatile fatty acid increased quadratically. Digestibility of dry matter, organic matter, neutral detergent fiber, acid detergent fiber, nonfiber carbohydrate, and crude protein increased quadratically with increasing ADY supplementation. Supplementation of ADY did not affect blood concentration of total protein, triglyceride, aspartate aminotransferase, and alanine aminotransferase, whereas blood urea nitrogen, cholesterol, and nonesterified fatty acid concentrations decreased quadratically with increasing ADY supplementation. Methane production was not affected by ADY supplementation when expressed as grams per day or per kilogram of actual milk yield, dry matter intake, digested organic matter, and digested nonfiber carbohydrate, whereas a trend of linear and quadratic decrease of CH4 production was observed when expressed as grams per kilogram of fat-corrected milk and digested neutral detergent fiber. In conclusion, feeding ADY to early-lactating cows improved lactation performance by increasing nutrient digestibility. The optimal ADY dose should be 20 g/d per head.

13.
J Virol Methods ; 288: 114030, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33275927

RESUMO

Quick and accurate detection of SARS-CoV-2 is critical for COVID-19 control. Dozens of real-time reverse transcription PCR (qRT-PCR) assays have been developed to meet the urgent need of COVID-19 control. However, methodological comparisons among the developed qRT-PCR assays are limited. In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). The three qRT-PCR assays exhibited similar sensitivities, with the limit of detection (LoD) at about 10 copies per reaction (except the ORF 1b gene assay in CCDC assays with a LoD at about 100 copies per reaction). No cross reaction with other respiratory viruses were observed in all of the three qRT-PCR assays. Wide linear detection ranges from 106 to 101 copies per reaction and acceptable reproducibility were obtained. By using 25 clinical specimens, the N gene assay of IPBCAMS assays and CCDC assays performed better (with detection rates of 92 % and 100 %, respectively) than that of the WHO assays (with a detection rate of 60 %), and the ORF 1b gene assay in IPBCAMS assays performed better (with a detection rate of 64 %) than those of the WHO assays and the CCDC assays (with detection rates of 48 % and 20 %, respectively). In conclusion, the N gene assays of CCDC assays and IPBCAMS assays and the ORF 1b gene assay of IPBCAMS assays were recommended for qRT-PCR screening of SARS-CoV-2.

14.
Food Chem ; : 128737, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33277125

RESUMO

In this work, capsaicin (CAP) was loaded into mesoporous silica nanoparticles (MSNs) with grain diameters of 50 nm, 100 nm and 400 nm by free diffusion to obtain the support materials Cap@MSN-50, Cap@MSN-100 and Cap@MSN-400, respectively. The loading capacity was separately calculated as 854.77, 713.86 and 649.09 (mg/g Cap/MSN) by ultraviolet spectrophotometry. An IFFM-E flow injection chemiluminescent analyzer was used for the slow-release experiment, which demonstrated that the MSN release of CAP proceeded with a slow-release effect and MSNs with a smaller grain diameter had a higher rate of slow release and stronger oxidation resistance. The prepared materials were used to maintain the freshness of ground beef by modified atmosphere packaging. After more than 5 days of storage, Cap@MSN-50 retained better oxidation resistance than CAP. The results show that loading CAP into mesoporous nanomaterials has the potential application value for long-term preservation and oxidation prevention of some foods.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33280594

RESUMO

BACKGROUND: Sepsis is a life-threatening disease caused by the dysregulated host response to the infection, and being the major cause of death to patients in intensive care unit (ICU). OBJECTIVE: Early diagnosis of sepsis could significantly reduce in-hospital mortality. Though generated from infection, the development of sepsis follows its own psychological process and disciplines, alters with gender, health status and other factors. Hence, the analysis of mass data by bioinformatic tools and machine learning is a promising method for exploring early diagnosis manners. METHODS: We collected miRNA and mRNA expression data of sepsis blood samples from Gene Expression Omnibus (GEO) and ArrayExpress databases, screened out differentially expressed genes (DEGs) by R software, predicted miRNA targets on TargetScanHuman and miRTarBase websites, conducted Gene Ontology (GO) term and KEGG pathway enrichment based on overlapping DEGs. The STRING database and Cytoscape were used to build protein-protein interaction (PPI) network and predict hub genes. Then we constructed a Random Forest model by using the hub genes to assess sample type. RESULTS: Bioinformatic analysis of GEO dataset revealed 46 overlapping DEGs in sepsis. The PPI network analysis identified five hub genes, SOCS3, KBTBD6, FBXL5, FEM1C and WSB1. Random Forest model based on these five hub genes was used to assess GSE95233 and GSE95233 datasets, and the area under curve (AUC) of ROC are 0.900 and 0.7988, respectively, which confirmed the efficacy of this model. CONCLUSION: The integrated analysis of gene expression in sepsis and the effective Random Forest model built in this study may provide promising diagnostic methods for sepsis.

16.
BMC Infect Dis ; 20(1): 931, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287722

RESUMO

BACKGROUND: Evaluate the safety and efficacy of 104-week regimen of Telbivudine(LdT)-based optimization strategy for Chinese patients who have chronic hepatits B(CHB) with HBeAg-negative. METHODS: This multi-center, open-label, prospective study enrolled 108 HBeAg-negative CHB patients who received LdT (600 mg/day) for 24 weeks, Adefovir (ADV) was added if HBV DNA remained detectable at week 24, otherwise LdT was maintained to use until 104 weeks. HBV DNA, alanine amino transferase (ALT), hepatitis B surface antigen(HBsAg), creatinine kinase(CK), and estimated glomerular filtration rate (eGFR) were measured, safety was assessed. RESULTS: Eighty-eight patients (81%) had HBV-DNA undetectable at 24 weeks and maintained to receive LdT monotherapy until 104 weeks, whereas the other 20 patients had HBV-DNA detectable and ADV was used in combination. For all patients, 72% of patients reached ALT normalization at 24 weeks, which increased to 80% at 52 weeks and 104 weeks, respectively.. 81% of total patients had undetectable HBV-DNA at 24 weeks, 92% at 52 weeks, and 94% at 104 weeks. The HBsAg titre declined steadily from baseline to 104 weeks (3.62 vs. 2.98 log10 IU/mL, p < 0.05), and the eGFR increased steadily from baseline to 104 weeks (92.9 vs. 104.4 mL/min/1.73 m2, p < 0.05). Although 79 patients (73%) had at least one time of elevated CK, most of these patients had CK elevated in Grade 1/2. CONCLUSIONS: LdT was well tolerated and effective, and 94% of patients achieved virological suppression after 104 weeks. TRIAL REGISTRATION: This study was registered in clinicaltrials.gov on January 31, 2012 and the ID No. was NCT01521975 .

17.
Onco Targets Ther ; 13: 11645-11658, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33223838

RESUMO

Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer-related deaths, with the liver as the most common site of distant metastasis. The prognosis of CRC with liver metastasis is poor, and most patients cannot undergo surgery. In addition, conventional antitumor approaches such as chemotherapy, radiotherapy, targeted therapy, and surgery result in unsatisfactory outcomes. In recent years, immunotherapy has shown good prospects in the treatment of assorted tumors by enhancing the host's antitumor immune function, and it may become a new effective treatment for liver metastasis of CRC. However, challenges remain in applying immunotherapy to CRC with liver metastasis. This review examines how the microenvironment and immunosuppressive landscape of the liver favor tumor progression. It also highlights the latest research advances in immunotherapy for colorectal liver metastasis and identifies immunotherapy as a treatment regimen with a promising future in clinical applications.

18.
Sci Rep ; 10(1): 19917, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199803

RESUMO

Propionate has been reported to exert antidepressant effects, but high-dose propionate may induce autism-like symptoms in experimental animals through induction of dysbiosis of neurotransmitters. The bi-directional effects of propionate seem to be dose-dependent. However, due to the pathological discrepancies between depression and autism, conclusions drawn from autism may not be simply transferable to depression. The effect and underlying action mechanisms of high-dose propionate on depression remains undetermined. To investigate the effects of propionate on depression, propionate dose gradients were intravenously administrated to rats exposed to chronic unpredictable mild stress (CUMS) for 1 week. Results of these behavioral tests demonstrate that low-dose propionate (2 mg/kg body weight/day) induces antidepressant effect through bodyweight recovery, elevated reward-seeking behaviors, and reduced depression-like behaviors, while high-dose propionate (200 mg/kg body weight/day) induces prodepressant effects opposite of those of low-dose propionate. A comprehensive profiling of neurotransmitters in the hippocampus demonstrated that CUMS induces reduction of NE (Norepinephrine), DA (Dopamine). GABA (γ-aminobutyric acid) was recovered by low-dose propionate, while high-dose propionate exerted more complicated effects on neurotransmitters, including reduction of NE, DA, 5-Hydroxytryptamine and Tryptophan, and increase of GABA, Kynurenine, Homovanillic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine. The neurotransmitters disturbed by high-dose propionate suggest metabolic disorders in the hippocampus, which were confirmed by the clear group separation in PCA of metabolomic profiling. The results of this study demonstrate the double-edged dose-dependent effects of propionate on depression and suggest potential cumulative toxicity of propionate as a food additive to mood disorders.

19.
Front Genet ; 11: 586415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133170

RESUMO

Tumor-infiltrating T-lymphocytes are defined as T-lymphocytes that infiltrated into tumor tissues; however, their composition, clinical significance, and underlying mechanism in hepatocellular carcinoma (HCC) and adjacent non-tumor tissues are still not completely understood. Herein, we collected marker genes of T cell subpopulations from a previous study and estimated their relative infiltrating levels in HCC and adjacent non-tumor tissues. Specifically, the infiltrating levels of all the T cells were significantly reduced in HCC as compared with non-tumor tissues. Unsupervised clustering of the HCC samples by the T cell infiltrating levels revealed that the HCC samples could be clearly classified into two groups. The driver genes, including PTK2B, ATM, PIK3C2B, and KIT, and several CNAs were observed to be associated with reduced T cell infiltrating levels. Particularly, deletion of TP53 more frequently occurred in low T cell infiltration HCC samples and resulted in its downregulation and cell cycle progression, indicating that cell cycle progression was closely associated with reduced T cell infiltration. In contrast, for the samples with high infiltration T cells, its immune evasion might be regulated by the immune checkpoint regulators, such as PD-1/PD-L1 and CTLA4. Moreover, Olaparib, one of the PARP inhibitors, and immune checkpoint inhibitors might be therapeutic candidates for the samples from the two T cell infiltrating clusters. Clinically, the tumor-infiltrating levels of cytotoxic CD4 cell, Mucosal associated invariant T (MAIT) cell, and exhausted CD8+ T cell might be used as predictors for vascular invasion, recurrence, and overall survival. Collectively, we systematically evaluated the clinical significance and potential molecular mechanisms of tumor-infiltrating T cell subpopulations in hepatocellular carcinoma, which might broaden our insights into the immunological features of HCC and provide potential immunotherapeutic targets.

20.
Analyst ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146162

RESUMO

Brombuterol is a new emerging ß-adrenergic agonist that has been used as an additive in animal feed to enhance the lean meat-to-fat ratio. Due to its potential harm to consumers, it is urgent to develop sensitive, simple and rapid analytical methods to monitor brombuterol residue. In this study, a competitive lateral flow immunochromatographic assay (FLIA) based on surface-enhanced Raman scattering (SERS) was developed for ultrasensitive quantitative determination of brombuterol in swine liver, pork and feed samples. Ag@Au core-shell bimetallic nanoparticles with the highest SERS enhancement were synthesized, characterized and used as the substrate for preparation of the immunoprobe AgMBA@Au-Ab, in which the Raman reporter mercaptobenzoic acid (MBA) was embedded between the core-shell layers and monoclonal antibodies against brombuterol were immobilized on the surfaces of nanoparticles. The presence of brombuterol was identified through a color change on testing lines. In addition, quantitative detection of brombuterol was achieved by measuring the characteristic Raman peak intensity of MBA in the immunoprobes captured by the coating antigen. The IC50 and limit of detection (LOD) of the SERS-based FLIA for brombuterol were 45 pg mL-1 and 0.11 pg mL-1, respectively. The recoveries of brombuterol from spiked samples were in the range of 87.27-100.16% with relative standard deviations of 1.29%-6.99% (n = 3). The proposed SERS-based LFIA was proven to be a feasible method for ultrasensitive and rapid detection of brombuterol and might be a platform for sensitive and rapid detection of a broad range of analytes in clinical, environmental and food analyses.

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