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Objective@#The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.@*Methods@#In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.@*Results@#We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.@*Conclusion@#These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.
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Humans , Amino Acids , COVID-19/epidemiology , Genomics , Mutation , Phylogeny , SARS-CoV-2/geneticsABSTRACT
Ferroptosis is a new type of cell death caused by abnormal accumulation of iron-dependent reactive oxygen species （ROS） and imbalance of redox with the participation of iron ions. In recent years， studies have found that ferroptosis is associated with various diseases and can especially regulate the development of tumors. Chinese medicine has unique advantages in tumor prevention and treatment. How to use ferroptosis theory to guide the prevention and treatment of cancer and other tumor diseases by Chinese medicine is a new research hotspot. This paper summarizes the proposal， action mechanism， and signaling pathway of ferroptosis， its application in tumor therapy， and the research on the activity of Chinese medicine based on ferroptosis. Results found that the occurrence of ferroptosis is related to iron metabolism， lipid ROS metabolism， and other signaling pathways and gene expressions. Ferroptosis can regulate tumor initiation and development， treatment， and tumor immunity， which provides strategies for tumor treatment and anti-tumor drug development. By analyzing the biological activity of Chinese medicine against ferroptosis， we found that Chinese medicines （Scutellariae Radix， Puerariae Lobatae Radix， Astragali Radix， Ginkgo， Epimedii Folium， Artemisiae Annuae Herba， and Salviae Miltiorrhizae Radix et Rhizoma）， Chinese herbal compounds （ Naotaifang， Si Junzitang， and Shenmai injection）， and Chinese medicine effective components （baicalein， dihydroartemisinin， puerarin， piperlongumine， luteolin， and quercetin） can exert antitumor and other biological activities by regulating ferroptosis. Therefore， Chinese medicine has great potential in preventing and controlling tumors and other diseases by regulating ferroptosis. This paper provides theoretical basis and research ideas for the in-depth study of ferroptosis theory and guides the prevention and treatment of tumor diseases by Chinese medicine.
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OBJECTIVE@#To evaluate systematically the efficacy and safety of COVID-19 vaccines.@*METHODS@#PubMed, Embase, Cochrane Library, Clinicaltrial.gov, CNKI, Wanfang Data, China Biomedical Literature Service System, and China Clinical Trial Registry were searched for randomized controlled trials of COVID-19 vaccines published up to December 31, 2020. The Cochrane bias risk assessment tool was used to assess the quality of studies. A qualitative analysis was performed on the results of clinical trials.@*RESULTS@#Thirteen randomized, blinded, controlled trials, which involved the safety and efficacy of 11 COVID-19 vaccines, were included. In 10 studies, the 28-day seroconversion rate of subjects exceeded 80%. In two 10 000-scale clinical trials, the vaccines were effective in 95% and 70.4% of the subjects, respectively. The seroconversion rate was lower than 60% in only one study. In six studies, the proportion of subjects who had an adverse reaction within 28 days after vaccination was lower than 30%. This proportion was 30%-50% in two studies and > 50% in the other two studies. Most of the adverse reactions were mild to moderate and resolved within 24 hours after vaccination. The most common local adverse reaction was pain or tenderness at the injection site, and the most common systemic adverse reaction was fatigue, fever, or bodily pain. The immune response and incidence of adverse reactions to the vaccines were positively correlated with the dose given to the subjects. The immune response to the vaccines was worse in the elderly than in the younger population. In 6 studies that compared single-dose and double-dose vaccination, 4 studies showed that double-dose vaccination produced a stronger immune response than single-dose vaccination.@*CONCLUSIONS@#Most of the COVID-19 vaccines appear to be effective and safe. Double-dose vaccination is recommended. However, more research is needed to investigate the long-term efficacy and safety of the vaccines and the influence of dose, age, and production process on the protective efficacy.
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Aged , Humans , COVID-19 , COVID-19 Vaccines , China , SARS-CoV-2 , VaccinesABSTRACT
Objective: To investigate the multi compound-target-pathway mechanism of Renshen Baidu Powder (RSBDS) in the treatment of COVID-19 from cytokine perspective. Methods: The active compounds of RSBDS were collected by TCMSP and the cytokine storm related targets were collected by the drug target database. The interaction network of RSBDS on single drug-active compounds-targets was established by Cytoscape. The interaction network, GO function and KEGG pathway of the targets were analyzed by String and DAVID databases. Results: The interaction network of RSBDS on single drug-active compounds-targets included 10 kinds of medicinal materials, 211 active compounds and 151 disease targets. Interaction network showed that the targets related to the inhibition to cytokine storm of RSBDS on COVID-19 might include STAT3, MAPK1, NFκB1, PIK3CA, MAPK3, TNF, CXCR4, VEGFA, IL-6, IL-2, etc. GO function showed that above targets in biological function involved chemotaxis and steroid metabolism; Molecular function entries involved heme binding, iron ion binding and oxygen binding; Cell composition entries involved cell surface and cell membrane. KEGG pathway showed that above targets participated in the regulation of Chagas disease, HIF-1 signaling pathway, TNF signaling pathway, etc. Conclusion: The multi compound-target-pathways effect of RSBDS on COVID-19 was realized by inhibiting cytokine storm, which through regulating chemotaxis, increasing blood oxygen saturation, inhibiting STAT, MAPK, NFκB, PIK3K and IL-6 signal pathways.
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Objective: To study the potential anti-inflammatory active ingredient of Chinese herbal Polygoni Cuspidati Rhizoma et Radix. Method: The inflammatory model of peritoneal macrophages (RAW264.7 cells) induced by lipopolysaccharide (LPS) in mice was used to screen out the anti-inflammatory activity of 95% ethanol extract of Polygoni Cuspidati Rhizoma et Radix and its macroporous resin elution site (30%, 60%, 95% ethanol eluting site). The characteristic fingerprints were established by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology, and then partial least squares method (partial least squares, PLS) was used to study the spectrum-effect relationship between the peak area of the characteristic components and the inhibition rate of nitric oxide (NO), and potential anti-inflammatory active ingredients were identified according to variable important in projection (VIP). Result: The ethanol extract macroporous resin 60% ethanol elution site of Polygoni Cuspidati Rhizoma et Radix had the strongest inhibition ability of nitric oxide formation, with a certain dose-dependent relationship. The study of spectrum-effect relationship showed that 3 components had potential anti-inflammatory activity, namely Emodin-8-O-β-D-glucoside (E-8-G), Emodin-1-O-β-D-giucoside, and Emodin-8-O-(6'-O-malonyl)-glucoside. In addition, the anti-inflammatory activity of E-8-G was further validated at the cell level through molecular docking analysis. Conclusion: Three potential anti-inflammatory active ingredients were found base on the spectrum-effect relationship. This study strategy is helpful to find the active ingredients (group) of traditional Chinese medicine, and provides new research ideas and methods for studying the material basis of Chinese herbal medicine.
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OBJECTIVE@#To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR).@*METHODS@#The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed.@*RESULTS@#After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (P＜0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (P＜0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (P＜0.01).@*CONCLUSION@#The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.
Subject(s)
Child , Humans , Apoptosis , Daunorubicin , PTEN Phosphohydrolase , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal TransductionABSTRACT
Vascular dementia [VD] models were made first by repeating cerebral ischemia-reperfusion and followed by treating with estrogen. Learning-memory ability was measured by Morris water maze. Concentration of Ca[2+] in hippocampus was determined by Fura-2/AM fluorescence probe and the expression of Calbindin-D28K [CB] in hippocampal CA1 was tested by immunohistochemistry. Learning-memory ability was improved in E group rats; Concentration of Ca[2+] in hippocampus was decreased in E group rats. The expression of CB was less in E group rats. It implies that estrogen could improve learning-memory ability in VD rats, which may be associated with suppressing intracellular Ca[2+] overload and increasing the expression of CB in hippocampus
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<p><b>OBJECTIVE</b>To study the role of Helicobacter pylori (H. pylori) infection in newly diagnosed childhood immune thrombocytopenia (ITP).</p><p><b>METHODS</b>A total of 495 children with newly diagnosed ITP who were hospitalized for the first time between January 2011 and December 2013 were included as the case group. A total of 123 children with common respiratory tract infection (not ITP or other diseases of blood system) were randomly selected as the control group. All patients were divided into four groups by age: <1 year group, 1-3 years group, 3-7 years group, and 7-14 years group. The incidence of H. pylori infection in all age groups and the clinical outcomes of ITP children with or without H. pylori infection were retrospectively analyzed.</p><p><b>RESULTS</b>The incidence rate of H. pylori infection in the case group increased with increasing age. There was no significant difference in the incidence rate of H. pylori infection between the case and the control groups among subjects of the same age (P>0.05). All the ITP patients were not given anti-H. pylori treatment and only received the treatment (glucocorticoid and/or immunoglobulin) for ITP, and their remission rate declined with increasing age. There was no significant difference in the remission rate between the ITP children with H. pylori infection and those without H. pylori infection in the same age group (P>0.05).</p><p><b>CONCLUSIONS</b>H. pylori infection may not be a major cause of ITP in children, and the clinical outcomes of children with acute ITP are not affected by receiving anti-H. pylori treatment or not.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Age Factors , Helicobacter Infections , Epidemiology , Helicobacter pylori , Incidence , Purpura, Thrombocytopenic, IdiopathicABSTRACT
<p><b>OBJECTIVE</b>To study the effect of exogenous Ca2+ on photosynthetic parameters of Pinellia ternate and accumulations of active components under high temperature stress.</p><p><b>METHOD</b>The pigment contents of P. ternata leaves, photosynthesis parameters and chlorophyll fluorescence parameters of P. ternata leaves, the contents of guanosine, adenosine and polysaccharide in P. ternata tubers were measured based on different concentrations of exogenous Ca2+ in heat stress when the plant height of P. ternata was around 10 cm.</p><p><b>RESULT</b>The contents of total chlorophyll and ratio of chlorophyll a/b were relatively higher by spaying Ca2+. Compared with the control, spaying 6 mmol x L(-1) Ca2+ significantly enhanced the net photosynthetic rate (Pn), transpiration (Tr) and stomatal limitation (L8), but reduced intercellular CO2 concentration (C) in P. ternata leaves. With the increase of Ca2+ concentration, maximal PS II efficiency (Fv/Fm), actual photosynthetic efficiency (Yield) and photochemical quenching coefficient (qP) initially increased and then decreased, however, minimal fluorescence (Fo) and non-photochemical quenching coefficient (NPQ) went down first and then went up. The contents of guanosine and polysaccharide and dry weight of P. ternata tubers showed a tendency of increase after decrease, and the content of adenosine increased with the increase of Ca2+ concentration. The content of guanosine and polysaccharide in P. ternata tubers and its dry weight reached maximum when spaying 6 mmol x L(-1) Ca2+.</p><p><b>CONCLUSION</b>With the treatment of calcium ion, the inhibition of photosynthesis and the damage of PS II system were relieved in heat stress, which increased the production of P. ternata tubers.</p>