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Lunar soils record the history and spectral changes resulting from the space-weathering process. The solar wind and micrometeoroids are the main space-weathering agents leading to darkening (decreasing albedo) and reddening (increasing reflectance with longer wavelength) of visible and near-infrared spectra. Nevertheless, their relative contributions are not well constrained and understood. In this study, we examine the near-infrared spectral variation as a function of lunar latitude and chemical composition using remote spectroscopic analysis of mare basalts and swirl regions. The results indicate that the reflectance of lunar mature soils darkens and the spectral slope flattens (reddening effect saturation) in areas of enhanced solar wind flux. We propose a previously unrecognized stage of space weathering (the post-mature stage), in which solar wind implantation may contribute to the growth and coarsening of metallic iron particles into larger microphase iron. This space-weathering mechanism is dominated by the solar wind and has important implications for understanding the alteration processes of airless bodies across our solar system.
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Na4MnV(PO4)3 (NMVP) has gained attention for its high redox potential, good cycling stability, and competitive price but suffers from poor intrinsic electronic conductivity and Jahn-Teller effect from Mn3+. In this work, cation/anion doping strategy was used for Aspergillus niger-bioderived carbon-coated NMVP (NMVP/AN) to improve the structural stability and electrochemical performance, where Al3+ doping inhibited the dissolution of Mn and enhanced the Mn3+/Mn2+ redox pair activity; besides, F- doping not only weakens the Na2-O bond but also endows the hierarchical and porous structure of NMVP/AN, which led to a more rapid and fluid transfer of Na+. The elaborately designed Na3.9Mn0.9Al0.1V(PO4)3/AN (NMAVP/AN) exhibits 105.9 mA h g-1 at 0.5 C, and the as-prepared Na3.1MnV(PO3.7F0.3)3/AN (NMVPF/AN) delivers 104.1 mA h g-1 at 5 C. Further demonstration of the hard carbon//NMAVP/AN full cell manifests the good potential of Al3+-doped NMVP/AN for practical applications (100.6 mA h g-1 at 1 C). These findings open up the possibility of unlocking the high-performance Na superionic conductor (NASICON).
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BACKGROUND: The coexistence of esophageal variceal bleeding and superficial esophageal cancer (SEC) is relatively rare in clinical practice. Moreover, there have been few reports of SEC overlying esophageal varices (EVs). Herein, we report our successful use of endoscopic submucosal dissection (ESD), esophageal solitary venous dilatation (ESVD), and endoscopic injection sclerotherapy (EIS) to treat a 75-year-old man who was diagnosed with SEC coexisting with esophageal variceal bleeding. CASE SUMMARY: A 75-year-old man was admitted to the hospital due to black stool for 4 days. The patient had a history of liver cancer, cirrhosis, and portal hypertension. Endoscopic examination revealed esophageal and gastric varicose veins, as well as esophageal carcinoma in situ. We first treated esophageal variceal bleeding by ESVD and EIS. One week later, ESD treatment was done, and the complete resection of early esophageal cancer was successfully completed via endoscopy. There were no postoperative complications, such as bleeding, infection, or perforation. CONCLUSION: The sequential treatment of ESVD, EIS, and ESD is an effective method for treating EVs with early esophageal cancer.
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This meta-analysis aimed to evaluate the efficacy of sorafenib plus transcatheter arterial chemoembolization (TACE) in treating hepato-cellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Twelve randomized controlled trials published until 28th Sep 2022 were finally included. Of the total 1746 patients, of whom 458 received sorafenib and TACE treatment (Group S+TACE), and 1288 only underwent TACE (Group TACE), were enrolled. Outcomes including time to progression (TTP), objective response rate (ORR), disease control rate (DCR), overall survival (OS), survival rate (SR), and adverse reactions, were extracted. The OS (HR: 0.596, 95 %CI: 0.507-0.685, p < 0.001; I2 = 0.0 %) and TTP (HR: 0.379, 95 %CI: 0.205-0.553, p < 0.001; I2 = 4.5 %) in the S+TACE group were longer than those in the TACE group. The ORR (RR: 2.101, 95 %CI: 1.555-2.839, p < 0.001; I2 = 0.0 %), DCR (RR: 1.547, 95 %CI: 1.126-2.126, p = 0.007; I2 = 79.6 %) and SR (RR: 1.416, 95 %CI: 1.183-1.694, p < 0.001; I2 = 83.8 %) in the S+TACE group were higher than those in the TACE group. Compared with the TCAE group, the higher odds of HFSR, oral ulcer, and diarrhea among patients with HCC complicated by PVTT were discovered in the S+TACE group. The marginal significance was found in ascites and gastrointestinal bleeding between the two groups. Sorafenib plus TACE has good efficacy and mild adverse reactions, which may be worthy of clinical promotion.
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Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Veia Porta , Sorafenibe , Trombose Venosa , Humanos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Veia Porta/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa/etiologia , Trombose Venosa/patologia , Trombose Venosa/terapiaRESUMO
Raman spectroscopy has emerged as a crucial mineral analysis technique in planetary surface exploration missions. Nonetheless, the inherently low Raman scattering efficiency of planetary silicate materials makes it challenging to extract enough Raman information. Theoretical and experimental studies of the remote Raman scattering properties of planetary materials are also urgent requirements for future lunar and planetary explorations. Here, Shandong University Remote Raman Spectrometer (SDU-RRS) was developed to demonstrate the feasibility of lunar remote Raman technology and conduct preliminary research on remote Raman scattering properties. SDU-RRS utilizes a pulsed 532 nm laser, a non-focal Cassegrain telescope, a volume phase holographic grating, an intensified charge-coupled device, and the time-gating technique to detect weak-signal silicate minerals. The spectral resolution obtained with atomic emission lamps was <4.91 cm-1, and the wavelength accuracy was <1 cm-1, across the spectral range of 241-2430 cm-1. SDU-RRS can detect natural augite within a feldspar-olivine-augite matrix at a concentration of 20 % at â¼1 m under ambient lighting conditions. A series of experiments were conducted to evaluate the influence of measurement conditions and physical matrix effects on acquired Raman signals, either qualitatively or quantitatively, on geological materials. The study indicates that the transmission of Raman-scattered light conforms to Lambert's cosine law, and a linear correlation exists between Raman intensity and laser power. The study also evaluated the impact of grain size, surface roughness, porosity, and shadow-hiding effects. Reducing grain size decreases Raman intensity and broadens Raman spectra. These characteristics are essential for achieving definitive mineralogical information from granular materials by remote Raman spectroscopy in lunar and planetary explorations.
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The Weyl semimetals represent a distinct category of topological materials wherein the low-energy excitations appear as the long-sought Weyl Fermions. Exotic transport and optical properties are expected because of the chiral anomaly and linear energy-momentum dispersion. While three-dimensional Weyl semimetals have been successfully realized, the quest for their two-dimensional (2D) counterparts is ongoing. Here, we report the realization of 2D Weyl Fermions in monolayer PtTe1.75, which has strong spin-orbit coupling and lacks inversion symmetry, by combined angle-resolved photoemission spectroscopy, scanning tunneling microscopy, second harmonic generation, X-ray photoelectron spectroscopy measurements, and first-principles calculations. The giant Rashba splitting and band inversion lead to the emergence of three pairs of critical Weyl cones. Moreover, monolayer PtTe1.75 exhibits excellent chemical stability in ambient conditions, which is critical for future device applications. The discovery of 2D Weyl Fermions in monolayer PtTe1.75 opens up new possibilities for designing and fabricating novel spintronic devices.
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Duodeno , Corpos Estranhos , Perfuração Intestinal , Humanos , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Duodeno/lesões , Duodeno/diagnóstico por imagem , Duodeno/cirurgia , Masculino , Tomografia Computadorizada por Raios X , FemininoRESUMO
Latent fingerprints, as one of the most frequently encountered traces in crime scene investigation and also one of the largest sources of forensic evidence, can play a critical role in determining the identity of a person who may be involved in a crime. Due to the invisible characteristic of latent fingerprints, exploring efficient techniques to visualize them (especially the ones resided on metallic surfaces) while retain the biological and chemical information (e.g., touch DNA) has become a multidisciplinary research focus. Herein we reported a new and highly sensitive electrochemical interfacial strategy of simultaneously developing and enhancing latent fingerprints on stainless steel based on synchronous electrodeposition and electrochromism of manganese oxides in a neutral aqueous electrolyte. By utilizing a specially designed device for electrochemical testing and image capture, a series of electrochemical measurements, physical characterization and image analysis have been applied to evaluate the feasibility, development accuracy and enhancement efficacy of the proposed electrochemical system. The qualitative and quantitative analysis on the in situ and ex situ fingerprint images indicates that the three levels of fingerprint features can be precisely developed and effectively enhanced. Forensic DNA typing has also been performed to reveal actual impact of the proposed electrochemical system on subsequent analysis of touch DNA in fingerprint residues. The ratio of detected loci after electrochemical treatment reaches up to 98.5 %, showing non-destructive nature of this fingerprint development and enhancement technique.
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Sodium (Na) super ion conductor (NASICON) structure Na3MnTi(PO4)3 (NMTP) is considered a promising cathode for sodium-ion batteries due to its reversible three-electron reaction. However, the inferior electronic conductivity and sluggish reaction kinetics limit its practical applications. Herein, we successfully constructed a three-dimensional cross-linked porous architecture NMTP material (AsN@NMTP/C) by a natural microbe of Aspergillus niger (AsN), and the structure of different NMTP cathodes was optimized by adjusting different transition metal Mn/Ti ratios. Both approaches effectively altered the three-dimensional NMTP structure, not only improving electronic conductivity and controlling Na+ diffusion pathways but also enhancing the electrochemical kinetics of the material. The resultant AsN@NMTP/C-650, sintered at 650 °C, exhibits better electrochemical performance with higher reversible three-electron reactions corresponding to the voltage platforms of Ti4+/3+, Mn3+/2+, and Mn4+/3+ around 2.1, 3.6, and 4.1 V (vs Na+/Na), respectively. The capacity retention rate is up to 89.3% after 1000 cycles at a 2C rate. Moreover, a series of results confirms that the Na3.4Mn1.2Ti0.8(PO4)3 cathode has the most excellent electrochemical performance when the Mn/Ti ratio is 1.2/0.8, with a high capacity of 96.59 mAh g-1 and 97.1% capacity retention after 500 cycles.
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BACKGROUND: Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality. It requires urgent interventions in order to improve outcomes. Intravenous immunoglobulins (IVIG) are considered as potential therapy in sepsis patients. Results of trials on IVIG as adjunctive therapy for sepsis have been conflicting due to the variability in population characteristics, country geography and drug dosage form in different studies. METHODS: A systematic article search was performed for eligible studies published up to January, 31, 2023, through the PubMed, Embase, Cochrane Library and Chinese National Knowledge Infrastructure database. The included articles were screened by using rigorous inclusion and exclusion criteria. Subgroup analyses were conducted according to different IVIG types, ages and economic regions. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. RESULTS: In total, 31 randomized controlled trials were included with a sample size of 6,276 participants. IVIG could reduce the mortality (RR 0.86, 95% CI: 0.77-0.95, p = 0.005), the hospital stay (MD - 4.46, 95% CI: - 6.35 to - 2.57, p = 0.00001), and the APACHE II scores (MD - 1.65, 95% CI: - 2.89 to - 0.63, p = 0.001). Additionally, the results showed that IgM-enriched IVIG was effective in treating sepsis (RR 0.55, 95% CI: 0.40 - 0.76; p = 0.0003), while standard IVIG failed to be effective (RR 0.91, 95% CI: 0.81-1.02, p = 0.10). And the effect of IVIG in reducing neonatal mortality was inconclusive (RR 0.93, 95% CI: 0.81-1.05, p = 0.24), but it played a large role in reducing sepsis mortality in adults (RR 0.70, 95% CI: 0.57-0.86, p = 0.0006). Besides, from the subgroup of different economic regions, it indicated that IVIG was effective for sepsis in high-income (RR 0.89, 95% CI: 0.79-0.99, p = 0.03) and middle-income countries (RR 0.49, 95% CI: 0.28-0.84, p = 0.01), while no benefit was demonstrated in low-income countries (RR 0.56, 95% CI: 0.27-1.14, p = 0.11). CONCLUSIONS: There is sufficient evidence to support that IVIG reduces sepsis mortality. IgM-enriched IVIG is effective in both adult and neonatal sepsis, while standard IVIG is only effective in adult sepsis. IVIG for sepsis has shown efficacy in high- and middle-income countries, but is still debatable in low-income countries. More RCTs are needed in the future to confirm the true clinical potential of IVIG for sepsis in low-income countries.
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Imunoglobulinas Intravenosas , Sepse , Humanos , Imunoglobulina M , Imunoglobulinas Intravenosas/uso terapêutico , Tempo de Internação , Sepse/tratamento farmacológicoRESUMO
Background: Human parvovirus B19 (B19V) is a common contaminant found in plasma pools and plasma derivatives. Previous studies were mainly focused on limited aspects, further assessment of prevalence of B19V DNA and antibodies in plasma donors, the contamination of B19V in pooled plasma and plasma derivatives should be performed in China. Study Design and Methods: Individual plasma donors' samples from four provinces and pooled plasma from four Chinese blood product manufacturers were collected and screened using B19V DNA diagnostic kits between October 2018 and May 2020. The positive samples were investigated for the seroprevalence of B19V antibodies and subjected to sequence analysis and alignment for phylogenetic studies. Moreover, 11 plasma donors who were B19V DNA-positive at their first testing were also followed during the later donation period. Additionally, 400 plasma pools and 20 batches of plasma derivatives produced by pooled plasma with a viral load of B19V DNA exceeding 104IU/mL were also collected and tested for B19V DNA and antibodies. Objectives: To comprehensively and systematically determine the frequency and viral load of B19V DNA in plasma donors, pooled plasma, and plasma derivatives from four Chinese blood product manufacturers. Results: A total of 17,187 plasma donors were analyzed and 44 (0.26%) specimens were found positive for B19V DNA. The quantitative DNA levels ranged from 1.01 × 101 to 5.09 × 1012 IU/mL. Forty-four DNA-positive specimens were also investigated for the seroprevalence of B19V antibodies, 75.0% and 2.3% of which were seropositive for B19V IgG and IgM antibodies, respectively. The phylogenic analyses showed that the prevalent genotypes in the four provinces' plasma donors belonged to B19V Genotype 1. Eleven individual plasma donors who were B19V DNA-positive at the first donation were then followed for a period, and in general, the DNA levels of B19V gradually decreased. Moreover, 64.8% (259/400) of the pooled plasma was contaminated by B19V, with concentrations of 1.05 × 100-3.36 × 109IU/mL. Approximately 72.6% of the DNA-positive plasma pools were only moderately contaminated (<104 IU/mL), while 27.4% contained >104 IU/mL. Twenty batches of plasma derivatives produced by pooled plasma with a viral load of B19V DNA exceeding 104IU/mL were also tested. B19V was detected in 5/5 PCC samples and 5/5 factor VIII samples but was not found in the intravenous immune globulin and albumin samples. Conclusion: The contamination of B19V in pooled plasma and plasma-derived clotting factor concentrates is serious. Whether B19V nucleic acid testing (NAT) screening of plasma and plasma derivatives is launched in China, blood product manufacturers should spontaneously perform B19V NAT screening in plasma donors and mini-pool plasma. These measures can ensure that samples with high titer B19V DNA are discarded in order to prevent and control this transfusion transmitted virus.
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Anticorpos Antivirais , Doadores de Sangue , DNA Viral , Parvovirus B19 Humano , Humanos , DNA Viral/sangue , População do Leste Asiático , Parvovirus B19 Humano/genética , Filogenia , Reação em Cadeia da Polimerase , Estudos Soroepidemiológicos , Anticorpos Antivirais/sangueRESUMO
Alzheimer's disease (AD) is a common neurodegenerative disease that currently has no known cure. Intravenous immunoglobulin (IVIG), which contains AD-related antibodies and has anti-inflammatory properties, has shown potential as a treatment for AD. However, the efficacy of clinical trials involving AD patients treated with IVIG has been inconsistent. Our previous study found that different IVIGs had significantly varied therapeutic effects on 3xTg-AD mice. In order to investigate the relationship between the composition and function of IVIG and its efficacy in treating AD, we selected three IVIGs that showed notable differences in therapeutic effects. Then, the concentrations of specific antibodies against ß-amyloid (Aß)42, tau, and hyperphosphorylated tau (p-tau) in three IVIGs, as well as their effects on systemic inflammation induced by lipopolysaccharide (LPS) in Balb/c mice, were analyzed and compared in this study. The results indicated that these IVIGs differed greatly in anti-Aß42/tau antibody concentration and anti-p-tau ratio, and improved LPS-stimulated peripheral inflammation, liver and kidney injury, and neuroinflammation in Balb/c mice to varying degrees. Combined with our previous results, the efficacy of IVIG against AD may be positively correlated with its level of AD-related antibodies and anti-inflammatory ability. AD-related antibody analysis and functional evaluation of IVIG should be given sufficient attention before clinical trials, as this may greatly affect the therapeutic effect of AD treatment.
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Doença de Alzheimer , Doenças Neurodegenerativas , Camundongos , Animais , Doença de Alzheimer/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Lipopolissacarídeos , Anticorpos/uso terapêutico , Peptídeos beta-Amiloides , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Proteínas tau , Camundongos TransgênicosRESUMO
This article aims to summarize the development and challenges of real-world data (RWD) and real-world evidence (RWE) in China and introduce a unique opportunity for medical devices to gain accelerated regulatory approval in China by utilizing RWE generated in a free trade pilot zone "Boao Lecheng" in Hainan Province. In 2020, the National Medical Products Administration (NMPA) issued a draft guideline on the "Use of real-world data to support clinical evaluation for medical devices", suggesting that RWE derived from RWD could support clinical evaluation throughout the life cycle of a medical device. Meanwhile, the Chinese government has allowed qualified RWD collected in Boao Lecheng to support registration application of innovative medical devices and drugs in China. These medical devices and drugs should have been approved abroad, but not in China yet, and met urgent and unmet medical needs in China. The article also presents the successful story of an innovative Glaucoma drainage tube as the first medical device approved in China using RWE generated in Boao Lecheng in 2020. Although we are witnessing an increased interest in RWE, a few challenges remain, e.g., limited data accessibility and data sharing, concerns on data quality, etc. Collaborations among relevant stakeholders in the RWE research are vital to address the challenges.
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Background and objectives: The adverse effects of plasma donation on the body has lowered the odds of donation. The aim of this study was to investigate the prevalence of abnormal serum calcium and total serum protein related to plasma donation, identify the influencing factors, and come up with suggestions to make plasma donation safer. Methods: Donors from 10 plasmapheresis centers in five provinces of China participated in this study. Serum samples were collected before donation. Serum calcium was measured by arsenazo III colorimetry, and the biuret method was used for total serum protein assay. An automatic biochemical analyzer was used to conduct serum calcium and total serum protein tests. Results: The mean serum calcium was 2.3 ± 0.15 mmol/L and total serum protein was 67.75 ± 6.02 g/L. The proportions of plasma donors whose serum calcium and total serum protein were lower than normal were 20.55% (815/3,966) and 27.99% (1,111/3,969), respectively. There were significant differences in mean serum calcium and total serum protein of plasma donors with different plasma donation frequencies, gender, age, regions, and body mass index (BMI), (all p < 0.05). Logistic regression analysis revealed that donation frequencies, age, BMI and regions were significantly associated with a higher risk of low serum calcium level, and donation frequencies, gender, age and regions were significant determinants factors of odds of abnormal total serum protein. Conclusions: Donation frequencies, gender, age, regions, and BMI showed different effects on serum calcium and total serum protein. More attention should be paid to the age, donation frequency and region of plasma donors to reduce the probability of low serum calcium and low total serum protein.
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Doadores de Sangue , Cálcio , Humanos , Índice de Massa Corporal , Proteínas Sanguíneas , China/epidemiologiaRESUMO
BACKGROUND: High blood glucose level is one of the main characteristics of diabetes mellitus. Based on previous studies, it is speculated longevity families may have certain advantages in blood glucose regulation. However, limited information on these items has been reported. The purpose of this study was to profile differences of plasma proteomics between longevity subjects (with normal fructosamine (FUN) level) and non-longevity area participants (with exceeding standard FUN level). METHODS: In this study, a TMT-based proteomics analysis was used to profile differences of plasma proteomics between longevity subjects (with normal FUN level) and non-longevity area participants (with exceeding standard FUN level). Results were validated by Luminex detection. RESULTS: A total of 155 differentially expressed proteins (DEPs) were identified between these two groups. The DEPs related to blood glucose regulation were mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism and propanoate metabolism, and most of the DEPs were contained in carbohydrate metabolism, PI3K-Akt pathway, glucagon signaling pathway and inflammatory response. Validation by Luminex detection confirmed that CD163 was down-regulated, and SPARC, PARK 7 and IGFBP-1 were up-regulated in longevity participants. CONCLUSIONS: This study not only highlighted carbohydrate metabolism, PI3K-Akt pathway, glucagon signaling pathway and inflammatory response may play important roles in blood glucose regulation, but also indicated that YWHAZ, YWHAB, YWHAG, YWHAE, CALM3, CRP, SAA2, PARK 7, IGFBP1 and VNN1 may serve as potential biomarkers for predicting abnormal blood glucose levels.
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BACKGROUND: Blood derivatives therapy is a conventional clinical treatment, while the treatment for Alzheimer's disease (AD) is relatively novel. To provide clinical references for treating AD, this meta-analysis was performed to evaluate the efficacy and safety of blood derivatives therapy on the patients with AD. METHODS: A systematic articles search was performed for eligible studies published up to December 6, 2021 through the PubMed, Embase, Cochrane library, ClinicalTrials.gov , Chinese National Knowledge Infrastructure database, and Wanfang databases. The included articles were screened by using rigorous inclusion and exclusion criteria. Study selection and data-extraction were performed by two authors independently. Random effects model or fixed effects model was used. Quality of studies and risk of bias were evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.4. The study was designed and conducted according to the Preferring Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. RESULTS: A total of three plasma administrations (two plasma exchange and one young plasma infusion) and five intravenous immunoglobulin (IVIG) randomized controlled trials with a sample size of 1148 subjects diagnosed with AD were included. There was no significant difference in cognitive improvement and all-cause discontinuation between intervention and placebo groups (RR 1.10, 95% CI 0.79-1.54). And Intervention groups showed not a statistically significant improvement in cognition of included subjects measured by the ADAS-Cog (MD 0.36, 95% CI 0.87-1.59), ADCS-ADL (MD -1.34, 95% CI - 5.01-2.32) and NPI (MD 2.20, 95% CI 0.07-4.32) score compared to the control groups. IVIG is well tolerated for AD patients even under the maximum dose (0.4 g/kg), but it is inferior to placebo in Neuropsychiatric Inventory scale in AD patients (MD 2.19, 95% CI 0.02-4.37). CONCLUSIONS: The benefits of blood derivatives therapy for AD are limited. It is necessary to perform well-designed randomized controlled trials with large sample sizes focusing on the appropriate blood derivatives for the specific AD sub-populations in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021233886.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Imunoglobulinas Intravenosas , Cognição , Grupos Controle , PlasmafereseRESUMO
Growth differentiation factor 11 (GDF11), belonging to the transforming factor-ß superfamily, regulates anterior-posterior patterning and inhibits neurogenesis during embryonic development. However, recent studies recognized GDF11 as a rejuvenating (or anti-ageing) factor to reverse age-related cardiac hypertrophy, repair injured skeletal muscle, promote cognitive function, etc. The effects of GDF11 are contradictory and the mechanism of action is still not well clarified. The objective of the present study was to investigate effects of GDF11 on PC12 neural stem cells in vitro and to reveal the underlying mechanism. We systematically assessed the effects of GDF11 on the life activities of PC12 cells. GDF11 significantly suppressed cell proliferation and migration, promoted differentiation and apoptosis, and arrested cell cycle at G2/M phase. Both TMT-based proteomic analysis and phospho-antibody microarray revealed PI3K-Akt pathway was enriched when treated with GDF11. Inhibition of ALK5 or PI3K obviously attenuated the effects of GDF11 on PC12 neural stem cells, which exerted that GDF11 regulated neural stem cells through ALK5-dependent PI3K-Akt signaling pathway. In summary, these results demonstrated GDF11 could be a negative regulator for neurogenesis via ALK5 activating PI3K-Akt pathway when it directly acted on neural stem cells.
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Células-Tronco Neurais , Proteínas Proto-Oncogênicas c-akt , Animais , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células PC12 , Proteômica , Fatores de Diferenciação de Crescimento/metabolismo , Transdução de Sinais , Células-Tronco Neurais/metabolismoRESUMO
Background: The outbreak of COVID-19 has resulted in more than 200 million infections and 4 million deaths. The blood derivative therapy represented by intravenous immunoglobulin (IVIG) and convalescent plasma (CP) therapy may be the promising therapeutics for COVID-19. Methods: A systematic article search was performed for eligible studies published up to August 3, 2021, through the PubMed, Embase, Cochrane Library. The included articles were screened by using rigorous inclusion and exclusion criteria. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. Results: A total of 5 IVIG therapy and 13 CP therapy randomized controlled trials were included with a sample size of 13,696 subjects diagnosed with COVID-19. IVIG could reduce the mortality compared with the control group (RR 0.65, 95% CI: 0.46-0.93, p = 0.02). The use of CP did not effectively reduce the mortality (RR 0.97, 95% CI: 0.91-1.03, p = 0.38), the length of hospital stay (MD -0.47, 95% CI: -4.13 to 3.20, p = 0.80), and the mechanical ventilation use (RR = 0.98, 95% CI: 0.89-1.07, p = 0.62) of the patients with COVID-19. Treatment with IVIG or CP was not significantly associated with an increase in reported adverse events (RR 1.07, 95% CI: 0.94-1.22, p = 0.28). Conclusions: Treatment with IVIG could be effective and safe to improve survival for patients with COVID-19. But the benefit of CP in the treatment of COVID-19 is limited. The certainty of the evidence was moderate for all outcomes.