ABSTRACT
OBJECTIVE@#To assess the effectiveness of Jiuwei Zhuhuang Powder (JWZH), a Tibetan patent medicine in treating upper respiratory tract infection (URTI) associated cough in children.@*METHODS@#The study was a multicenter, randomized, open-label, controlled trial. A total of 142 children aged 2 to 14 years old, with URTI-associated cough within 48 h of onset, were randomly assigned to two groups at a 1:1 ratio by computer-generated randomization sequence. Children were treated with JWZH (1 to 1.5 g, twice to thrice daily) in the treatment group or conventional treatment (Pediatric Paracetamol, Artificial Cow-bezoar and Chlorphenamine Maleate Granules, 0.25 to 1 g, thrice daily) in the control group for 5 days. The primary endpoints were the time to cough resolution and 4-day cough resolution rate. The secondary endpoints were the daily improvement in symptom scores and cough resolution rate during the study period.@*RESULTS@#A total of 138 children were included in the intention-to-treat analysis, with 71 cases in the treatment group and 67 cases in the control group. Compared with the conventional treatment, the children receiving JWZH had a shorter time to cough resolution [hazard ratio, 2.10; 95% confidence interval (CI), 1.29-3.40; P=0.003]. The median time to cough resolution for children receiving JWZH was shorter than that of the conventional treatment (2 days vs. 3 days; P<0.001). The 4-day cough resolution rate in the JWZH group was higher than that of the control group (94.4% vs. 74.6%; risk difference: 19.8%, 95% CI: 8.1%-31.5%; relative risk: 1.265, 95% CI: 1.088-1.470; P=0.001). There were no statistically significant differences in the improvement of other symptoms caused by URTI (P>0.05). Adverse events was reported in 5.6% (4/71) and 4.5% (3/67) in participants of JWZH and PPACCM groups (P>0.05), respectively, which were all mild and resolved without treatment.@*CONCLUSION@#JWZH seemed to be a safe and effective therapy for URTI-associated cough in children. (Trial registration No. ChiCTR2000039421).
Subject(s)
Child , Humans , Cough/drug therapy , Drugs, Chinese Herbal , Nonprescription Drugs , Powders , Respiratory Tract Infections/drug therapyABSTRACT
Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.
Subject(s)
Humans , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/metabolism , Cell Line, Tumor , DNA/therapeutic use , Glioblastoma/metabolism , Radiation, Ionizing , Temozolomide/therapeutic useABSTRACT
Objective:To investigate the difference of heart rate variability in cardioinhibitory type vasovagal syncope(VVS-CI) children with different body mass index(BMI).Methods:Clinical data of thirty-four children with syncope or pre-syncope were retrospectively analyzed, who visited specialist clinic for syncope and diagnosed as VVS-CI at the Second Xiangya Hospital of Central South University from January 2012 to December 2019.BMI was calculated based on height and weight, and divided into lean group(BMI≤18.4 kg/m 2, n=19) and normal group(BMI 18.5-23.9 kg/m 2, n=15). Heart rate variability(HRV) of 24 h dynamic electrocardiogram was analyzed using linear analysis method.Time domain index included SDNN, SDANN, rMSSD and pNN50.Frequency domain index included total power(TP), ultra low frequency power(ULF), very low frequency power(VLF), low frequency power(LF), high frequency power(HF) and LF/HF. Results:There was no significant difference in SDNN, SDANN and rMSSD between lean and normal group( P>0.05), but pNN50 increased in lean group( P<0.05). No significant differences were found in TP, ULF, LF, HF and LF/HF between two groups( P>0.05), while VLF was lower in lean group than that in normal group( P<0.05). There was no statistical difference in time domain index and frequency domain index between different gender between lean and normal group( P>0.05). SDNN, SDANN and LF were higher in<12 years old than those in≥12 years old in lean group( P<0.05). There was no statistical difference in rMSSD, pNN50, TP, ULF, VLF, HF and LF/HF( P>0.05). ULF increased and LF decreased in<12 years old compared to ≥12 years old in normal group( P<0.05). No statistical differences were found in SDNN, SDANN, rMSSD, pNN50, TP, VLF, HF and LF/HF( P>0.05). Conclusion:The autonomic nervous regulation function of VVS-CI children with low BMI and normal BMI is different, resulting in HRV difference.There were also differences in HRV between<12 years old and ≥12 years old with the same BMI.
ABSTRACT
Objective:To investigate the relationship between body mass index (BMI) and response time of cardioinhibitory type vasovagal syncope (VVS-CI) in children.Methods:The clinical data of 56 children with syncope or pre-syncope were retrospectively analyzed and they visited specialist clinic for syncope and were diagnosed as VVS-CI in the Second Xiangya Hospital, Central South University from December 2012 to September 2019.Based on height and weight, BMI was calculated, and divided into low BMI group (35 cases) and normal BMI group (21 cases). Between the 2 groups, baseline heart rate, head-up tilt test (HUTT) positive response heart rate, baseline head-up tilt test (BHUT) positive response time, and sublingual nitroglycerin-provocated HUTT (SNHUT) positive response time were compared.The correlation between BMI and positive response time was analyzed.SPSS 22.0 software was applied for statistical analysis.Results:There were no significant differences in age, sex, duration of disease and number of syncope between the 2 groups (all P>0.05). No significant differences were found in baseline heart rate and positive response heart rate between the 2 groups [(78.5±15.3) times/min vs.(72.8±8.7) times/min, t=1.223, P=0.230; (44.0±13.9) times/min vs.(47.0±10.0) times/min, t=-0.664, P=0.511]. Compared with normal BMI group, BHUT positive patients/SNHUT positive patients were higher in low BMI group (27/8 cases vs.9/12 cases, χ2=4.839, P=0.027), and the positive response time of BHUT was shorter [(13.1±4.6) min vs.(23.7±9.5) min, t=-2.691, P=0.023]. There were no significant differences in SNHUT positive response time between the 2 groups ( P>0.05). Low BMI was correlated with BHUT positive response time ( r=0.750, P=0.005). Normal BMI was not associated with BHUT positive response time ( r=0.316, P=0.217). There was no correlation between low BMI and normal BMI and SNHUT positive response time ( r=0.177, P=0.431; r=0.021, P=0.940). Conclusions:Low BMI is positively correlated with BHUT positive response time of children with VVS-CI.The time it takes for syncope occurrence was shorter in children with low BMI than that in normal BMI.
ABSTRACT
Antibiotic-associated diarrhea(AAD) is a frequent adverse effect of antibiotic in children.AAD is associated with longer hospitalization, higher healthcare cost and even lead to death.Pediatricians usually do not pay enough attention to AAD.Domestic experts from pulmonary medicine, infection and gastroenterology are organized to develop the consensus, to improve the diagnosis, treatment and prevention of AAD, and contribute the children health in future.
ABSTRACT
Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks ofBroussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1 (Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase (JAK) 2, signal transducer and activator of transcription (STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.
ABSTRACT
OBJECTIVE@#To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats.@*METHODS@#In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%～65% of the maximum oxygen consumption (V·O) to 70%～75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected.@*RESULTS@#The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P＜ 0.01). The expression level of SYN1 in rats was up-regulated significantly (P＜0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P＜0.01), while the expression level of CaMK IIα in young rats was down-regulated (P＜0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P＜ 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P＜0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P＜0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P＜0.01), and mTOR was also significantly up-regulated in the aged group (P＜0.05).@*CONCLUSION@#Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.
Subject(s)
Animals , Male , Rats , Age Factors , Cerebral Cortex , Physiology , Neuronal Plasticity , Physical Conditioning, Animal , Physical Endurance , Rats, Sprague-Dawley , Signal TransductionABSTRACT
OBJECTIVE@#To explore the effect of lentivirus-mediated BMP-2 overexpression plasmid transfection into bone marrow mesenchymal stem cells and silk fibroin scaffold on osteoblast transformation.@*METHODS@#The lentivirus BMP-2 overexpression vector was constructed, bone marrow mesenchymal stem cells were cultured, and the combined culture system of nuclear scaffolds was constructed. Alizarin red staining and alkaline phosphatase staining were used to detect the osteogenic transformation of bone marrow mesenchymal stem cells in vitro. Ten New Zealand white rabbits, weighing 3.2 to 4.5 kg(averaging 3.9 kg), aged (2.89±0.45) years old, were selected to construct the rabbit tibial defect model by drilling a conical tibial defect (5 mm in length, 2 mm in width and 3 mm in depth) with an oral drill. The repair of the tibial defect in the animal model was observed by HE staining. The experimental group was implanted with silk fibroin scaffold + BMP-2 overexpression vector bone marrow mesenchymal stem cell complex, while the negative control group was implanted with silk fibroin scaffold+non-transfected bone marrow mesenchymal stem cell complex.@*RESULTS@#Compared with the control group(silk fibroin scaffold+non-transfected bone marrow mesenchymal stem cells), the number of adherent cells on the surface of the scaffold in the experimental group(silk fibroin scaffold+transfected BMP-2 overexpression vector BMP-2 complex) increased significantly. Compared with the control group, the ECM secretion in the experimental group increased significantly. EDX analysis showed that the content of calcium ion was 0.22% in the control group and 0.86% in the experimental group, which showed that the ability of inducing calcium ion formation in the experimental group was stronger than that in the control group. Alizarin red staining of calcium nodules showed that there was no obvious change in the naked eye of the control group, and a small amount of calcium nodules could be seen under the microscope. In the experimental group, obvious red area staining was observed by naked eye, and a large number of calcium nodules were observed by microscopy. The results of alkaline phosphatase staining showed that there was no obvious change in the naked eye of the control group, and no obvious change in the microscopic observation. In the experimental group, purple area staining was observed by naked eyes, and ALP staining was strongly positive by microscopy. The combined culture system of silk fibroin scaffold and bone marrow mesenchymal stem cells can repair cartilage defects. The repair effect of BMP-2 bone marrow mesenchymal stem cells after transfection is obviously better than that of non-transfection group. HE staining showed that inflammatory cells decreased and scaffolds disappeared slightly in the control group. In the experimental group, inflammatory cells were significantly reduced, scaffolds disappeared and angiogenesis was observed.@*CONCLUSIONS@#Lentivirus-mediated BMP-2 overexpression plasmid can promote BMSC to differentiate into osteocytes and secrete more extracellular matrix containing Ca²⁺ to promote bone defect repair.
Subject(s)
Animals , Rabbits , Bone Marrow Cells , Bone Morphogenetic Protein 2 , Cells, Cultured , Fibroins , Lentivirus , Mesenchymal Stem Cells , Osteoblasts , Osteogenesis , Plasmids , TransfectionABSTRACT
Small molecules with physiological or pharmacological activities need to interact with biological macromolecules in order to function in the body. As the protein with the highest proportion of plasma protein,serum albumin is the main protein binding to various endogenous or exogenous small molecules. Serum albumin interacts with small molecules in a reversible non-covalent manner and transports small molecules to target sites. Bovine serum albumin( BSA) is an ideal target protein for drug research because of its low cost and high homology with human serum albumin. The research on the interaction between drugs and BSA has become a hotspot in the fields of pharmacy,medicine,biology and chemistry. In this research,molecular docking method was used to study the interaction between three small ginsenosides with high pharmacological value( Rg_1,Rb_1,Ro) and bovine serum albumin( BSA),and the binding mode information of three ginsenosides interacting with BSA was obtained. The results of molecular docking showed that ginsenosides and amino acid residues in the active pocket of proteins could be combined by hydrophobic action,hydrogen bonding and electrostatic action. The interaction between small ginsenosides and bovine serum albumin is not the only form,and their interaction has many forms of force. The interaction between these molecules and various weak forces is the key factor for the stability of the complex. The results of this study can provide the structural information of computer simulation for the determination of the interaction patterns between active components and proteins of ginseng.
Subject(s)
Animals , Cattle , Binding Sites , Computer Simulation , Ginsenosides , Chemistry , Molecular Docking Simulation , Protein Binding , Serum Albumin, Bovine , Chemistry , Spectrometry, Fluorescence , ThermodynamicsABSTRACT
Regulatory T (Treg) cells is an indispensable subset of T lymphocyte with the ability of immunosuppression in the periphery.Thymus-derived Treg cells(CD4+CD25+FOXP3+Treg cells) play a fundamental role in maintaining immune homeostasis in vivo.Treg cells have been actively involved in the onset and development of major human diseases including malignant tumors, autoimmune diseases,infectious diseases,allergic diseases and graft versus host disease(GVHD).Exosomes are membranous vesicles of endosomal origin that released from multiple cells into the extracellular space.They are currently considered to be vehicles containing protein,RNA and MicroRNA which can been transferred to recipient cells to modulate their activity by cell-contact-independent mecha-nism.Exosomes have a great impact on the induction and proliferation of Treg cells,understanding the relation of them will lead to novel therapeutic approaches for cancer immunotherapy,treating autoimmunity,infection,allergy and organ transplantation.
ABSTRACT
Objective To investigate the effect of different concentrations of magnesium-calcium alloy extract on the expression of matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinase-3 (TIMP3) in human colonic epithelial NCM460 cells.Methods The different concentrations of extracts (the volume fraction was 10％,50％ and 100％ respectively) were made with magnesium-calcium alloy.The 5 × 106 L-1 NCM460 suspension was randomly divided into control group,experimental group 1,experimental group 2 and experimental group 3.The cells in the control group were cultured by 2 000 μL high glucose Dulbecco's modified Eagle's medium (containing 10％ volume fraction of fetal bovine serum).The cells in the experimental group 1,2 and 3 were cultured by 2 000 μL magnesium-calcium alloy extract with volume fraction of 10％,50％ and 100％ respectively.The expressions of MMP9 and TIMP3 mRNA in NCM460 cells was detected by real-time fluorescence quantitative polymerase chain reaction,and the expression of MMP9 and TIMP3 protein in NCM460 cells was detected by Western blot at after one,three and five days of cultivation respectively.Results The expression of MMP9 mRNA and TIMP3 mRNA in NCM460 cells of the experimental group 1,2 and 3 was significantly lower than that in the control group after one day of cultivation (P ＜ 0.05).After three and five days of cultivation,the expression of MMP9 mRNA in NCM460 cells of the experimental group 1 was significantly lower than that in the control group (P ＜ 0.05),but the expression of MMP9 mRNA in the NCM460 cells of the experimental group 2 and 3 was significantly higher than that in the control group and the experimental group 1 (P ＜ 0.05).The expression of MMP9 mRNA in NCM460 cells of the experimental group 3 was significantly higher than that in the experimental group 2 after five days of cultivation (P ＜ 0.05).The expression of MMP9 mRNA in NCM460 cells of the experimental group 1,2 and 3 after three and five days of cultivation was significantly higher than that after one day of cultivation(P ＜ 0.05).There was no significant difference in the expression of MMP9 mRNA in NCM460 cells of the experimental group 1 between three and five days of cultivation (P ＞ 0.05).The expression of MMP9 mRNA in NCM460 cells of the experimental group 2 and 3 after five days of cultivation was significantly higher than that after three days of cultivation(P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells of the experimental group 2 and 3 was significantly higher than that in the experimental group 1 after one day of euhivation (P ＜ 0.05).After three days of cultivation,the expression of TIMP3 mRNA in NCM460 cells of the experimental group 1,2 and 3 was significantly lower than that in the control group (P ＜ 0.05);the expression of TIMP3 mRNA in NCM460 cells of the experimental group 2 was significantly lower than that in the experimental group 1 and 3 (P ＜ 0.05).After five days of cultivation,the expression of TIMP3 mRNA in NCM460 cells of the experimental group 1,2 and 3 was significantly higher than that in the control group (P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells after three and five days of cultivation was significantly higher than that after one day of cultivation (P ＜ 0.05),and the expression of TIMP3 after five days of cultivation was significantly higher than that after three days of cultivation in the experimental group 1 (P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells after three days of cultivation was significantly lower than that after one day of cultivation (P ＜ 0.05),and the expression of TIMP3 after five days of cultivation was significantly higher than that after one and three days of cultivation in the experimental group 2 (P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells after five days of cultivation was significantly higher than that after one and three days of cultivation in the experimental group 3 (P ＜ 0.05).After five days of cultivation,there was no significant difference in the expression of MMP9 protein in NCM460 cells between the experimental group 1 and control group (P ＞ 0.05),the expression of MMP9 protein in NCM460 cells of the experimental group 2 and 3 was significantly higher than that in the control group and the experimental group 1 (P ＜ 0.05),but there was no significant difference in the expression of MMP9 protein in NCM460 cells between the experimental group 2 and 3 (P ＞ 0.05).After five days of cultivation,the expression of TIMP3 protein in NCM460 cells of the experimental group 1,2 and 3 was significantly higher than that in the control group (P ＜0.05);but there was no significant difference in the expression of TIMP3 protein in NCM460 cells among the experimental group 1,2and 3 (P ＞ 0.05).Conclusions The high concentration of magnesium-calcium alloy extract has certain influence on the expression of MMP9 and TIMP3 gene in NCM460 cells,which may lead to the early inflammatory reaction,and the mechanism may be related to the calcium ion concentration in the extract.
ABSTRACT
[Objective]To explore the diagnostic value of urine ErbB3 protein in clear cell renal cell carcinoma.[Methods]We collected 31 urine samples of clear cell renal cell carcinoma patients who received operations in the Urology Department of the First Affiliated Hospital of Sun Yat-Sen University from April 2,2016 to August 31,2016.Meanwhile we collected 50 urine samples of normal people as control.We tested the expression of urine ErbB3 protein in experimen-tal group and control group,and analyzed the differences between the two groups.Then we established the ROC curve of which diagnosing clear cell renal carcinoma by urine ErbB3 protein. Also,we analyzed the relation between ErbB3 pro-tein in urine and the patients'BMI,preoperative creatinine,tumor diameter and underlying diseases such as hyperten-sion and hyperglycemia.[Results]①The expression of urine ErbB3 protein in clear cell renal cell carcinoma group was significantly lower than normal group(P<0.001). ② When diagnosing clear cell renal carcinoma by ErbB3 protein,the AUC of ROC was 0.802(P<0.001). When setting the cutoff as 13.98 pg/mL,the max Youden index was 0.525,the sensitivity was 0.645 and the specificity was 0.880. The Kappa value of diagnostic test was 0.542(P<0.001). ③ There was no correlation between the ErbB3 content and patients'BMI,tumor diameter or preoperative creatinine by correlation analysis. Also,there was no correlation between the urine ErbB3 protein content and blood pressure or blood glucose.[Conclusion]The urine ErbB3 protein of clear cell renal cell carcinoma was significantly lower than normal people,and it is meaningful for applying urine ErbB3 protein to early diagnosis of clear cell renal cell carcinoma.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia.</p><p><b>METHODS</b>Blood samples were collected from 30 children with recurrent pneumonia (recurrent pneumonia group), 30 children with acute pneumonia (acute pneumonia group), and 30 healthy children (control group). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. The correlation between serum YKL-40 level and laboratory indices related to humoral immune function was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40 level for recurrent pneumonia.</p><p><b>RESULTS</b>The recurrent pneumonia group had a significantly higher serum YKL-40 level than the acute pneumonia and control groups (P<0.05). The acute pneumonia group had a significantly higher serum YKL-40 level than the control group (P<0.05). Serum levels of IgG and complement 4 in the recurrent pneumonia group were significantly lower than in the acute pneumonia group (P<0.05). Serum YKL-40 level was negatively correlated with serum IgG level (r=-0.309, P=0.047) and serum complement 4 level (r=-0.324, P=0.039). The area under the ROC curve of serum YKL-40 level for diagnosing recurrent pneumonia was 0.958 (95%CI: 0.921-0.994).</p><p><b>CONCLUSIONS</b>Humoral immune function is low in children with recurrent pneumonia. Serum YKL-40 may be involved in the occurrence of recurrent pneumonia and can be used as a reference index for diagnosing recurrent pneumonia.</p>
Subject(s)
Child, Preschool , Female , Humans , Male , Chitinase-3-Like Protein 1 , Blood , Complement C4 , Immunity, Humoral , Immunoglobulin G , Blood , Pneumonia , Allergy and Immunology , RecurrenceABSTRACT
In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancers. This review will focus on the emerging clinical data on the therapeutic role of immune checkpoint inhibitors, and potential strategies to enhance the efficacy of this class of compounds, in the context of gynecological cancers. It is anticipated that future biomarker-directed clinical trials will provide further insights into the mechanisms underlying response and resistance to immunotherapy, and help guide our approach to designing therapeutic combinations that have the potential to enhance the benefit of immunotherapy in patients with gynecologic cancers.
Subject(s)
Humans , Biomarkers , CTLA-4 Antigen , Immunotherapy , Tumor MicroenvironmentABSTRACT
Objective To investigate the incidence of the common respiratory viruses in children with respiratory tract infection and to compare the results among different ages and to analyze the relationship between wheezing of children and various viruses.Methods Nasopharyngeal secretions of 618 children with respiratory infection hospitalized were assayed for 7 respiratory viruses, including respiratory syncytial virus ,adenovirus, influenza A virus, influenza B virus, parainfluenza virus Ⅰ 、 Ⅱ、 Ⅲ.Results (1) A total of 166 cases, affected with viral etiology,were detected in 618 samples,and the total positive rate was 26.86％.The most common virus was RSV (17.96％), followed by PIV Ⅲ (5.99％), IFA (1.62％), ADV (0.81％), PIV Ⅰ (0.49％).Moreover, 1 case infected with RSV and PIVⅠ was included, with the positive rate 0.16％.(2)The positive rates were different in various ages, with 14d ～ ＜ 1-year 35.04％, 1 ～ ＜ 3-year 18.25％, 3 ～ ＜ 6-year 17.11％ and ≥ 6-year 9.26％.(3) There were differences of positive rate of viruses among different respiratory infectious diseases, and capillary bronchitis occupied the highest percentage(47.37％).(4)Among all the detected children, infants were more likely to whee in auscultation of lung, and RSV was the primary etiology.Conclusion RSV,which was the primary viral etiology in children with wheezing, was the most common virus leading to respiratory infection of children, followed by PIV Ⅲ.In the children with respiratory tract infection, the viral infection tends to occur in younger children.
ABSTRACT
<p><b>OBJECTIVE</b>To study the changes in gut microbiota and serum D-lactate level and their significance in children with recurrent pneumonia.</p><p><b>METHODS</b>The stool and blood samples were collected from 30 children with recurrent pneumonia (recurrent group), 30 children with acute pneumonia (acute group), and 15 children receiving surgical operation (surgery group). The 16S rRNA fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to determine the numbers of Bifidobacterium and Escherichia coli in stool samples, and the ratio between the logarithmic values of the numbers of Bifidobacterium and Escherichia coli (B/E value) was calculated. The serum D-lactate level was measured, and correlation analysis was performed.</p><p><b>RESULTS</b>The recurrent group had a significantly lower number of Bifidobacterium and a significantly lower B/E value than the acute group and the surgery group (P<0.05), as well as a significantly higher number of Escherichia coli than the surgery group (P<0.05). There was no significant difference in the number of Escherichia coli between the recurrent group and the acute group. The recurrent group had a significantly higher serum D-lactate level than the acute group and the surgery group (P<0.05). In the recurrent group, B/E value was negatively correlated with serum D-lactate level (r=-0.539, P<0.05).</p><p><b>CONCLUSIONS</b>Children with recurrent pneumonia may have biological and mechanical barrier damage in the intestinal mucosa.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Bacteria , Classification , Genetics , Bifidobacterium , Genetics , Escherichia coli , Genetics , Feces , Microbiology , Gastrointestinal Microbiome , Lactates , Blood , Pneumonia , Blood , Microbiology , Pathology , RecurrenceABSTRACT
The rhizome of Panax japonicus var. major have been used as the natural medicinal agent by Chinese traditional doctors for more than thousand years. Most of the therapeutic effects of P. japonicus var. major had been reported due to the presence of tetracyclic or pentacyclic triterpene saponins. In this study, Illumina pair-end RNA-sequencing and de novo splicing were done in order to understand the pathway of triterpenoid saponins in this species. The valid reads data of 15. 6 Gb were obtained. The 62 240 unigenes were finally obtained by de novo splicing. After annotation, we discovered 19 unigenes involved in ginsenoside backbone biosynthesis. Additionally, 69 unigenes and 18 unigenes were predicted to have potential function of cytochrome P450 and UDP-glycosyltransferase based on the annotation results, which may encode enzymes responsible for ginsenoside backbone modification. This study provides global expressed datas for P. japonicus var. major, which will contribute significantly to further genome-wide research and analysis for this species.
Subject(s)
Gene Expression Profiling , Panax , Genetics , Saponins , Sequence Analysis, RNAABSTRACT
Eight compounds were isolated from the leaves of Turpinia arguta by various chromatograhic techniques such as D101 macroporous resin, polyamide, Sephadex LH-20,and HPLC chromatography, and their structures were elucidated as rhoifolin (1), apigenin-7-O- [2"-O-alpha-L-rhamnopyranosyl-6"-O-alpha-L-rhamnopyranosyl] -beta-D-glucopyranoside (2), acacetin-7-O- [2"-O-alpha-L-rhamnopyranosyl-6"-O-beta-D-glucopyranosyl] -beta-D-glucopyranoside (3), acacetin-7-O- [2"-O-alpha-L-rhamnopyranosyl-6"-O-alpha-L-rhamnopyranosyl] -beta-D-glucopyranoside(neobudofficide, 4), luteolin-7-O-[2"-O-beta-D-glucopyranosyl] -beta-D-glucopyranoside (5), chrysoeiml-7-O-[2"-O-beta-D-glucopyranosyl] -beta-D-glucopyranoside (6), acacetin-7-O-alpha-L-rhamnopyranosyl-(1 --> 6) -O-beta-D-glucopyranoside (buddleoside, linarin, 7), and apigenin 6, 8-di-C-beta-D-glucopyranoside (8) on the basis of spectral data analysis. Compounds 3-8 were isolated from T. arguta for the first time. Compounds 2, 3 showed weak anti-inflammatory effect on LPS-stimulated RAW264.7 cell.
Subject(s)
Animals , Mice , Anti-Inflammatory Agents , Chemistry , Pharmacology , Cell Line , Drugs, Chinese Herbal , Chemistry , Pharmacology , Flavonoids , Chemistry , Pharmacology , Glycosides , Chemistry , Pharmacology , Magnoliopsida , Chemistry , Mass Spectrometry , Molecular Structure , Plant Leaves , ChemistryABSTRACT
P2X7 is the most important subtype of the ATP receptors known so far. Recent investigations showed that the downstream signaling pathway of P2X7 is coupled with several key inflammatory molecules including IL-1beta and IL-18, this suggests P2X7 might have roles in the inflammatory diseases. Moreover, attenuation of P2X7 by selective antagonists in vitro and knockout mice in vivo reducing the inflammatory response indicated that P2X7 is a potential therapeutic target for inflammatory diseases. However, most previous studies on P2X7 were focused on nerve system diseases most, while its effects in inflammatory respiratory diseases, especially in asthma, chronic obstructive pulmonary disease (COPD) and lung cancer have been poorly investigated. In this paper, we reviewed the research progress on the structure, distribution, biological activities of P2X7 and its relationship with inflammatory respiratory diseases including asthma, COPD and lung cancer, along with the development of P2X7 antagonist as therapeutics.
Subject(s)
Animals , Humans , Mice , Asthma , Drug Therapy , Metabolism , Inflammation , Drug Therapy , Metabolism , Interleukin-18 , Metabolism , Interleukin-1beta , Metabolism , Lung Neoplasms , Drug Therapy , Metabolism , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive , Drug Therapy , Metabolism , Purinergic P2X Receptor Antagonists , Therapeutic Uses , Receptors, Purinergic P2X7 , Chemistry , Genetics , Metabolism , Respiratory Tract Diseases , Drug Therapy , MetabolismABSTRACT
<p><b>BACKGROUND</b>Von Hippel-Lindau disease (VHL), a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems, has rarely been reported in Asia. We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability.</p><p><b>METHODS</b>Genomic deoxyribonucleic acid (DNA) extracted from peripheral blood was amplified by polymerase chain reaction (PCR) to three exons of the VHL gene in 9 members of the Chinese family with VHL disease. PCR products were directly sequenced. We estimated the effects of VHL gene mutation on the stability of pVHL, which is indicated by the free energy difference between the wild-type and the mutant protein (ΔΔG).</p><p><b>RESULTS</b>The Chinese family was classified as VHL type 1. Three family members, including two patients and a carrier, had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1. This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein. There was low stability of the VHL protein (the ΔΔG was 12.71 kcal/mol) caused by this missense mutation.</p><p><b>CONCLUSIONS</b>We first reported a family with this VHL gene mutation in Asia. This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma (RCC) phenotype displayed by this family. The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.</p>