Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.454
Filtrar
1.
Cardiovasc Diabetol ; 20(1): 158, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332579

RESUMO

BACKGROUND: Functional mitral regurgitation (FMR) is one of the most common heart valve diseases in diabetes and may increase left ventricular (LV) preload and aggravate myocardial stiffness. This study aimed to investigate the aggravation of FMR on the deterioration of LV strain in type 2 diabetes mellitus (T2DM) patients and explore the independent indicators of LV peak strain (PS). MATERIALS AND METHODS: In total, 157 T2DM patients (59 patients with and 98 without FMR) and 52 age- and sex-matched healthy control volunteers were included and underwent cardiac magnetic resonance examination. T2DM with FMR patients were divided into T2DM patients with mild (n = 21), moderate (n = 19) and severe (n = 19) regurgitation. LV function and global strain parameters were compared among groups. Multivariate analysis was used to identify the independent indicators of LV PS. RESULTS: The T2DM with FMR had lower LV strain parameters in radial, circumferential and longitudinal direction than both the normal and the T2DM without FMR (all P < 0.05). The mild had mainly decreased peak diastolic strain rate (PDSR) compared to the normal. The moderate had decreased peak systolic strain rate (PSSR) compared to the normal and PDSR compared to the mild and the normal. The severe FMR group had decreased PDSR and PSSR compared to the mild and the normal (all P < 0.05). Multiple linear regression showed that the regurgitation degree was independent associated with radial (ß = - 0.272), circumferential (ß = - 0.412) and longitudinal (ß = - 0.347) PS; the months with diabetes was independently associated with radial (ß = - 0.299) and longitudinal (ß = - 0.347) PS in T2DM with FMR. CONCLUSION: FMR may aggravate the deterioration of LV stiffness in T2DM patients, resulting in decline of LV strain and function. The regurgitation degree and months with diabetes were independently correlated with LV global PS in T2DM with FMR.

2.
Phys Rev Lett ; 126(25): 256401, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34241529

RESUMO

Impurity pinning has long been discussed to have a profound effect on the dynamics of an incommensurate charge density wave (CDW), which would otherwise slide through the lattice without resistance. Here, we visualize the impurity pinning evolution of the CDW in ZrTe_{3} using the variable temperature scanning tunneling microscopy. At low temperatures, we observe a quasi-1D incommensurate CDW modulation moderately correlated to the impurity positions, indicating a weak impurity pinning. As we raise the sample temperature, the CDW modulation gets progressively weakened and distorted, while the correlation with the impurities becomes stronger. Above the CDW transition temperature, short-range modulations persist with the phase almost all pinned by impurities. The evolution from weak to strong impurity pinning through the CDW transition can be understood as a result of losing phase rigidity.

3.
Chem Biol Interact ; : 109570, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34217686

RESUMO

Verapamil is reported to prevent scar formation. However, whether verapamil is involved in the ureteral stricture scar and the underlying mechanism need further investigation. Fibroblasts were isolated from ureteral scar tissues. TGF-ß1 stimulation was used to induce fibrosis of fibroblasts. Inhibition of CaMK II was achieved by shRNA transfection. CCK-8 was performed to evaluate cell viability. qRT-PCR was applied to determine the level of mRNA while western blotting was used to determine the level of proteins. Immunofluorescence was used to detect the level of vimentin, collagen I and collagen III. Primary fibroblasts was successfully isolated from ureteral scar tissues. TGF-ß1 stimulation was capable to induce collagen production and fibrosis in primary fibroblasts while inhibition of CaMK II attenuate collagen production. Overexpression of wild type CaMK II lead to further increase of collagen production upon TGF-ß1 stimulation while the mutated CaMK II did not exert this promotion. Treatment of verapamil inhibits TGF-ß1 induced collagen production via inhibiting CaMK II. In present study, we revealed a vital role of Verapamil and CaMK II in the formation of ureteral scar. Verapamil inhibited TGF-ß1 induced collagen fiber formation by regulating CaMK II. Our finding might provide new insight into mechanism of prevention and treatment of ureteral scar.

4.
J Alzheimers Dis ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34219730

RESUMO

BACKGROUND: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer's disease (AD); however, the exact effect and mechanism remain unknown. OBJECTIVE: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. METHODS: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. RESULTS: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-ß42 (Aß 42) and Aß 40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3ß (GSK3ß) inactivation via upregulating GSK3ß (pSer9). CONCLUSION: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aß production and tau phosphorylation, which is related to GSK3ß inactivation.

5.
Cell Mol Neurobiol ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34224050

RESUMO

Nogo proteins, also known as Reticulon-4, have been identified as myelin-derived inhibitors of neurite outgrowth in the central nervous system (CNS). There are three Nogo variants, Nogo-A, Nogo-B and Nogo-C. Recent studies have shown that Nogo-A/B is abundant in macrophages and may have a wider effect on inflammation. In this review, we focus mainly on the possible roles of Nogo-A/B on polarization and recruitment of macrophages and their involvement in a variety of inflammatory diseases. We then discuss the Nogo receptor1 (NgR1), a common receptor for Nogo proteins that is also abundant in microglia/macrophage in the CNS. Interaction of Nogo and NgR1 in microglia/macrophage may affect the adhesion and polarization of macrophages that are involved in multiple neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Overall, this review provides insights into the roles of Nogo proteins in regulating macrophage functions and suggests that, potentially, Nogo proteins maybe a new target in the treatment of inflammatory diseases.

6.
Orphanet J Rare Dis ; 16(1): 299, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217357

RESUMO

PURPOSE: To evaluate the efficacy and safety of everolimus and sirolimus in patients with tuberous sclerosis complex-associated angiomyolipomas (TSC-AML). MATERIALS AND METHODS: We performed a multi-institutional retrospective study of TSC-AML patients treated with oral everolimus 10 mg or sirolimus 2 mg per day for at least 3 months. Angiomyolipoma volume was estimated using orthogonal measurements by MRI or CT. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events. All analyses were performed using SPSS 19.0 software. RESULTS: Response rates were high in both groups. With the prolonged medication durations, the therapeutic efficacy of both agents became more significant. The TSC-AML volume reduction after 6 and 12 months was more pronounced in patients with everolimus than those with sirolimus. More than half of the patients treated with everolimus had ≥ 50% reduction, and approximately 80% of them had ≥ 30% reduction, which was higher than that in patients treated with sirolimus. Regarding safety, there was no significant difference in the incidence of AEs between the two groups. CONCLUSIONS: Both everolimus and sirolimus are excellent therapeutic options for TSC-AML. However, everolimus has a better therapeutic efficacy than sirolimus, particularly in reducing TSC-AML volume. Everolimus is therefore recommended as the first choice of therapy for TSC-AML.

7.
World J Surg Oncol ; 19(1): 203, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229720

RESUMO

BACKGROUND: To evaluate the outcomes of pancreaticogastrostomy and pancreaticojejunostomy after pancreatoduodenectomy with the help of a meta-analysis. METHODS: Randomized controlled trials comparing pancreaticogastrostomy and pancreaticojejunostomy were searched electronically using PubMed, The Cochrane Library, and EMBASE. Fixed and random-effects were used to measure pooled estimates. Research indicators included pancreatic fistula, delayed gastric emptying, postoperative hemorrhage, intraperitoneal fluid collection, wound infection, overall postoperative complications, reoperation, and mortality. RESULTS: Overall, 10 randomized controlled trials were included in this meta-analysis, with a total of 1629 patients. The overall incidences of pancreatic fistula and intra-abdominal collections were lower in the pancreaticogastrostomy group than in the pancreaticojejunostomy group (OR=0.73, 95% CI 0.55~0.96, p=0.02; OR=0.59, 95% CI 0.37~0.96, p=0.02, respectively). The incidence of B/C grade pancreatic fistula in the pancreaticogastrostomy group was lower than that in the pancreaticojejunostomy group, but no significant difference was observed (OR=0.61, 95%CI 0.34~1.09, p=0.09). Postoperative hemorrhage was more frequent in the pancreaticogastrostomy group than in the pancreaticojejunostomy group (OR=1.52; 95% CI 1.08~2.14, p=0.02). No significant differences in terms of delayed gastric emptying, wound infection, reoperation, overall postoperative complications, mortality, exocrine function, and hospital readmission were observed between groups. CONCLUSION: This meta-analysis suggests that pancreaticogastrostomy reduces the incidence of postoperative pancreatic fistula and intraperitoneal fluid collection but increases the risk of postoperative hemorrhage compared with pancreaticojejunostomy.


Assuntos
Pancreaticoduodenectomia , Pancreaticojejunostomia , Gastrostomia/efeitos adversos , Humanos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Mol Plant Pathol ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242483

RESUMO

Phytophthora species can infect hundreds of different plants, including many important crops, causing a number of agriculturally relevant diseases. A key feature of attempted pathogen infection is the rapid production of the redox active molecule nitric oxide (NO). However, the potential role(s) of NO in plant resistance against Phytophthora is relatively unexplored. Here we show that the level of NO accumulation is crucial for basal resistance in Arabidopsis against Phytophthora parasitica. Counterintuitively, both relatively low or relatively high NO accumulation leads to reduced resistance against P. parasitica. S-nitrosylation, the addition of a NO group to a protein cysteine thiol to form an S-nitrosothiol, is an important route for NO bioactivity and this process is regulated predominantly by S-nitrosoglutathione reductase 1 (GSNOR1). Loss-of-function mutations in GSNOR1 disable both salicylic acid accumulation and associated signalling, and also the production of reactive oxygen species, leading to susceptibility towards P. parasitica. Significantly, we also demonstrate that secreted proteins from P. parasitica can inhibit Arabidopsis GSNOR1 activity.

9.
Front Endocrinol (Lausanne) ; 12: 618580, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326810

RESUMO

Objective: To verify if patients with deep ovarian suppression following gonadotropin releasing hormone (GnRH) agonist long protocol may benefit from a modified GnRH antagonist protocol based on luteinizing hormone (LH) levels. Design: Retrospective cohort study. Setting: University-based hospital. Patients: 110 patients exhibited ultra-low LH levels during ovarian stimulation using GnRH agonist long protocol. Interventions: As all the embryos in the first cycle were exhausted without being pregnant, these patients proposed to undergo a second cycle of ovarian stimulation. 74 of them were treated with a modified GnRH antagonist protocol based on LH levels. Other 36 patients were still stimulated following GnRH agonist long protocol. Main Outcome Measure: The primary outcome was live birth rate (LBR). The second outcomes were biochemical pregnancy rate, clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and cancellation rate. Results: Reproductive outcomes were much better in the modified GnRH antagonist protocol. The OPR and LBR were much higher in the GnRH antagonist protocol group than in the GnRH agonist long protocol group [odds ratio (OR) 3.82, 95% confidence interval (CI) 1.47, 10.61, P=0.018; OR 4.33, 95% CI 1.38, 13.60, P=0.008; respectively]. Meanwhile, the cancellation rate was much lower in the GnRH antagonist protocol group (OR 0.13, 95% CI 0.02, 0.72; P=0.014). Mean LH level during stimulation did not have a predictive value on live birth. However, it was independently associated with the occurrence of ongoing pregnancy (OR 2.70, 95% CI 1.25, 5.85; P=0.01). The results of sensitivity analyses were consistent with the data mentioned above. The patients got completely different and excellent clinical outcomes in their second cycles stimulated with the modified GnRH antagonist protocol. Conclusion: Patients with deep ovarian suppression following GnRH agonist long protocol may benefit from a modified GnRH antagonist protocol based on LH levels.

10.
Phys Rev Lett ; 127(3): 030402, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34328769

RESUMO

We propose a new method to directly measure a general multiparticle quantum wave function, a single matrix element in a multi-particle density matrix, by quantum teleportation. The density matrix element is embedded in a virtual logical qubit and is nondestructively teleported to a single physical qubit for readout. We experimentally implement this method to directly measure the wave function of a photonic mixed quantum state beyond a single photon using a single observable for the first time. Our method also provides an exponential advantage over the standard quantum state tomography in measurement complexity to fully characterize a sparse multiparticle quantum state.

11.
Eur J Obstet Gynecol Reprod Biol ; 264: 206-211, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34329946

RESUMO

OBJECTIVE: To explore the development and pregnancy potential of non-pronuclear (0PN) zygote-derived embryos in conventional in vitro fertilization (IVF) cycles. STUDY DESIGN: Embryonic development in 1039 oocyte retrieval cycles and clinical outcomes of 659 frozen-thawed blastocyst transfer cycles were retrospectively studied. RESULTS: Developmental potential of embryos with different blastomere numbers on day 3 were inconsistent in 0PN and 2PN groups. For 0PN-derived embryos, blastocyst rate of fast developing embryos (75.4%) was similar to that of intermediately developing embryos (72.9%), but good quality blastocyst rate of the former (49.2%) was significantly higher than that of the later (39.6%). In 2PN group, intermediately developing embryos had the highest blastocyst rate (77.9%) and good quality blastocyst rate (51.5%) (statistically significant). Comparison of frozen-thawed transfer was carried out between 0PN- and 2PN-derived blastocysts. For both single (SBT) and double blastocyst transfer (DBT) groups, no statistical differences existed between 0PN- and 2PN-derived blastocysts in clinical pregnancy rates (45.2% and 49.1% in SBT group, 64.7% and 66.4% in DBT group), implantation rates (45.2% and 49.1% in SBT group, 41.2% and 47.7% in DBT group) and live birth rates (35.5% and 36.8% in SBT group, 52.9% and 51.2% in DBT group). CONCLUSION: The developmental characteristic of 0PN-derived embryos was different from that of 2PN-derived embryos in IVF cycles. 0PN-derived blastocysts could obtain acceptable clinical pregnancy and live birth, but more studies are needed to confirm the safety..

12.
Artigo em Inglês | MEDLINE | ID: mdl-34331554

RESUMO

The colonization of bacterial communities and biofilm formation on microplastics (MPs) have aroused great concern recently. However, the influence of time and polymer types on the structural and functional characteristics of biofilms remains unclear. In this study, three types of MPs (polyethylene, polypropylene, and polystyrene) were exposed for different time periods (10, 20 and 30 days) in seawater using a microcosm experiment. Microscopic spectroscopy and high-throughput gene sequencing techniques were used to reveal the temporal changes of structural and functional characteristics of MPs associated biofilms. The results indicate that the biofilm formation is affected by both the incubation time and the polymer type. In addition, bacterial diversity and community structure in the biofilms show selectivity towards seawater, and tend to shift over time and among different polymer types. Moreover, biofilms are shown to harbor plastic degrading bacteria, leading to the changes of functional groups and surface hydrophobicity, and thereby enhancing the biodegradation of MPs.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34331651

RESUMO

The relationship between socioeconomic and ecological environment becomes a significant factor influencing the regional sustainable development of resource-based cities (RBCs); how to coordinate the relationship between socioeconomic growth and ecological environment is the key problem to achieve sustainable development goals of RBCs. A comprehensive evaluation indicator system was constructed to research the coupling coordination level of RBCs in this paper; the dynamic DM model and the CCD model were adopted to measure the comprehensive level of the coupling coordination degree between socioeconomic and ecological environment of the 9 resource-based cities from 2008 to 2018 in Sichuan province. The results showed that the coupling coordination level was not ideal. Only two cities were located to the moderate coordination, and other cities were located to the primary coordination or tiny coordination. In addition, there was a significant difference between SE and EE, and the comprehensive evaluation score of SE was lower than that of EE in eight RBCs, which accounts for 88.89%. Based on this, we analyzed the reasons for the backward development of the socioeconomic system of the resource-based cities in order to provide relevant references for the transformation of the RBCs. Finally, the policy suggestions for the sustainable development of different types of RBCs were provided, involving improving the policy and financial support for enterprise transformation, promoting high-new technology to improve production efficiency, strengthening government guidance on industrial layout, stabilizing employment, and improving the social security system. This study offers a model of China's experience that might be beneficial for achieving sustainable development goals (SGDs) of other cities and countries.

14.
Acta Pharmacol Sin ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253875

RESUMO

Diabetic kidney disease (DKD) is one of the microvascular complications of diabetes mellitus and a major cause of end-stage renal disease with limited treatment options. Wogonin is a flavonoid derived from the root of Scutellaria baicalensis Georgi, which has shown a potent renoprotective effect. But the mechanisms of action in DKD are not fully elucidated. In this study, we investigated the effects of wogonin on glomerular podocytes in DKD using mouse podocyte clone 5 (MPC5) cells and diabetic mice model. MPC5 cells were treated with high glucose (30 mM). We showed that wogonin (4, 8, 16 µM) dose-dependently alleviated high glucose (HG)-induced MPC5 cell damage, accompanied by increased expression of WT-1, nephrin, and podocin proteins, and decreased expression of TNF-α, MCP-1, IL-1ß as well as phosphorylated p65. Furthermore, wogonin treatment significantly inhibited HG-induced apoptosis in MPC5 cells. Wogonin reversed HG-suppressed autophagy in MPC5 cells, evidenced by increased ATG7, LC3-II, and Beclin-1 protein, and decreased p62 protein. We demonstrated that wogonin directly bound to Bcl-2 in MPC5 cells. In HG-treated MPC5 cells, knockdown of Bcl-2 abolished the beneficial effects of wogonin, whereas overexpression of Bcl-2 mimicked the protective effects of wogonin. Interestingly, we found that the expression of Bcl-2 was significantly decreased in biopsy renal tissue of diabetic nephropathy patients. In vivo experiments were conducted in STZ-induced diabetic mice, which were administered wogonin (10, 20, 40 mg · kg-1 · d-1, i.g.) every other day for 12 weeks. We showed that wogonin administration significantly alleviated albuminuria, histopathological lesions, and p65 NF-κB-mediated renal inflammatory response. Wogonin administration dose-dependently inhibited podocyte apoptosis and promoted podocyte autophagy in STZ-induced diabetic mice. This study for the first time demonstrates a novel action of wogonin in mitigating glomerulopathy and podocytes injury by regulating Bcl-2-mediated crosstalk between autophagy and apoptosis. Wogonin may be a potential therapeutic drug against DKD.

15.
CNS Neurosci Ther ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255932

RESUMO

AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein-coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER-positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT-PCR and immunoblot analyses showed that the levels of GPER and phosphorylated µ-type opioid receptor (p-MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER-positive neurons in the RVM of Gper-Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER-positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.

16.
Stem Cell Res Ther ; 12(1): 378, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215321

RESUMO

BACKGROUND: Idiopathic pneumonia syndrome (IPS) is a non-infectious fatal complication characterized by a massive infiltration of leukocytes in lungs and diffuse pulmonary injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Conventional immunosuppressive treatments for IPS have poor therapeutic effects. Safe and effective treatments are not yet available and under explorations. Our previous study demonstrated that mesenchymal stem cells (MSCs) can alleviate IPS, but the mechanisms remain unclear. METHODS: Co-cultured pre-activated T cells and MSCs in vitro to observe the changes in the CCR2-CCL2 axis. By establishing an IPS mouse model and administering MSCs to further verify the results of in vitro experiments. RESULTS: Co-culture of pre-activated T cells with MSCs in vitro modulated the CCR2-CCL2 axis, resulting in quiescent T cells and polarization toward CCR2+CD4+ T cell subsets. Blocking CCR2-CCL2 interaction abolished the immunoregulatory effect of MSCs, leading to re-activation of T cells and partial reversion of polarizing toward CCR2+CD4+ T cells. In IPS mouse model, application of MSCs prolonged the survival and reduced the pathological damage and T cell infiltration into lung tissue. Activation of CCR2-CCL2 axis and production of CCR2+CD4+ T cells were observed in the lungs treated with MSCs. The prophylactic effect of MSCs on IPS was significantly attenuated by the administration of CCR2 or CCL2 antagonist in MSC-treated mice. CONCLUSIONS: We demonstrated an important role of CCR2-CCL2 axis in modulating T cell function which is one of the mechanisms of the prophylactic effect of MSCs on IPS.


Assuntos
Células-Tronco Mesenquimais , Pneumonia , Animais , Quimiocina CCL2/genética , Camundongos , Receptores CCR2/genética , Linfócitos T
17.
Emerg Microbes Infect ; : 1-48, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197281

RESUMO

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase Ⅰ clinical trials in humans. A Randomized, double-blind, placebo-controlled phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February, 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive vaccine (10, 25, and 50µg) or placebo (V-01: Placebo=4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed promising safety profile with approximately 25% vaccine related overall adverse events within 30 days and no grade 3 or worse adverse events. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10µg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in phase Ⅱ/Ⅲ clinical trials.

18.
Cancer Commun (Lond) ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197702

RESUMO

There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow-up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non-metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third-line to the first-line of treatment for different patient groups with detailed notes are provided.

19.
Int J Med Sci ; 18(13): 2997-3003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220328

RESUMO

Squamous cell cancer of head and neck (HNSCC) is the sixth most common malignancy worldwide. One of the most common HNSCC types is oral squamous cell carcinoma (OSCC), which is the fifth leading cause of cancer death in Taiwan. Tripartite motif 21 (TRIM21) has been reported to play an important role in different cancer types. We found a correlation between TRIM21 and survival of HNSCC patients, but little information exists about how altered TRIM21 expression contributes to tumorigenesis. Thus, we investigated the combined effect of TRIM21 polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of OSCC. Two single-nucleotide polymorphisms (SNPs) of TRIM21 (rs4144331, rs915956) from 1194 healthy controls and 1192 OSCC patients were analyzed by real-time PCR. Among 1632 smokers, TRIM21 polymorphism carriers with the betel-nut chewing habit had a ~4.8-fold greater risk of OSCC than TRIM21 wild-type carriers without the betel-nut chewing habit. After adjusting for other covariants, OSCC patients with G/T at TRIM21 rs4144331 had a high risk for distant metastasis compared with G/G homozygotes. This study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development. Thus, our findings suggest that this study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development and suggest that interactions between mutant genes may alter the susceptibility to OSCC.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34272668

RESUMO

Global warming is increasing the frequency and duration of heat waves, which is defined as when air temperature exceeds a threshold for more than specific consecutive days. Ecosystem around the globe will be impaired by heat waves just like the exposures to dangerously high temperatures as a public health threat to human. However, the knowledge of the response of lake and reservoir ecosystem to heat waves is largely unknown although it has been argued that climate warming may increase the incidence of harmful algal blooms. We examined the long-term trend of heat waves and how the variability of phytoplankton biomass responds to lake heat waves on a deep reservoir (Lake Qiandaohu). Long-term (1980-2020) meteorological observation in the lake watershed showed a significant warming trend of 0.36 °C per decade for the yearly average of daily average air temperature and the yearly average of daily maximum air temperature of 18.32 °C was observed in 2016. Meanwhile, a significant increasing number of heat wave events lasting longer was observed, and Lake Qiandaohu suffered an unusually severe lake heat wave in summer 2016. Significant correlations were found between the yearly average of daily maximum air temperature and heat days, heat wave events, and heat wave days. Nuisance phytoplankton bloom was found in Lake Qiandaohu by high frequency observation and remote sensing monitoring in summer 2016. Remote sensing estimation from two Landsat 8 Operational Land Imager (OLI) images showed that the average chlorophyll a (Chla) was 7.45 ± 4.89 µg/L on July 18 before heat wave and 18.96 ± 0.98 µg/L on August 19 during the heat wave. Two heat wave events lasting from July 20 to August 2 and August 11 to 26 with average surface water temperature of 29.93 and 31.99 °C promoted two marked phytoplankton blooms with average Chla concentrations of 11.75 ± 4.08 and 10.53 ± 1.65 µg/L in the central lake region, respectively, as evidenced by high-frequency buoy data. These findings suggest that heat waves are likely to yield an increased threat of harmful algal bloom in freshwater ecosystems. With lake heat waves projected to increase in frequency, duration, and spatial extent with global climate change, more studies are needed to improve our understanding of lake heat waves and their potential effects on the species, communities, frequency of phytoplankton bloom, and also help providing advanced schemes of water quality management.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...