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1.
International Eye Science ; (12): 34-38, 2022.
Article in Chinese | WPRIM | ID: wpr-906725

ABSTRACT

@#AIM: To explore the changes and significance in JIA-U and to detect the levels of CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup> regulatory B cells(Breg)in the peripheral blood of children with juvenile idiopathic arthritis-associated uveitis(JIA-U).<p>METHODS: From April 2018 to May 2020, 95 children with JIA-U were selected as JIA-U group; 70 children with juvenile idiopathic arthritis(JIA)were selected as JIA group, and all of them were diagnosed and treated in our hospital; another 75 healthy children in the same period were selected as the control group. The ratio of CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup>Breg in peripheral blood was detected by flow cytometry; the level of IL-10 in peripheral blood was detected by ELISA; the correlation between CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup>Breg ratio and the expression of IL-10, the severity of JIA-U patients was analyzed by Pearson correlation coefficient method; the influencing factors of JIA-U were analyzed by Logistic regression. <p>RESULTS: Compared with the control group, the proportion of CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup>Breg in peripheral blood of children in JIA group and JIA-U group was significantly lower(all <i>P</i><0.01), while the level of IL-10 was significantly higher(all <i>P</i><0.01); compared with JIA group, the proportion of CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+Breg</sup> in JIA-U group was significantly lower(<i>P</i><0.01), while the level of IL-10 was significantly higher(<i>P</i><0.01); compared with the stationary phase, the ratio of CD1d<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup>Breg in the active phase of JIA and JIA-U patients was significantly reduced(all <i>P</i><0.01), and the IL-10 level was significantly increased(all <i>P</i><0.01); the ratio of CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup>Breg was negatively correlated with the expression of IL-10 and the severity of JIA-U; multivariate analysis showed that low proportion of CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup>Breg, less-joint JIA subtype, duration of arthritis < 4a, high levels of IL-10 were risk factors for JIA-U. <p>CONCLUSION: The proportion of CDld<sup>(hi)</sup>CD5<sup>+</sup>CD19<sup>+</sup>Breg in peripheral blood of children with JIA-U is significantly decreased, which may be involved in the occurrence and development of JIA-U, and has the potential to be used as an index to judge the severity of JIA-U.

2.
Article in English | WPRIM | ID: wpr-928944

ABSTRACT

OBJECTIVE@#To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia.@*METHODS@#A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention.@*RESULTS@#The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05).@*CONCLUSION@#Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).


Subject(s)
Acupuncture Points , Analgesia, Obstetrical/adverse effects , Analgesia, Patient-Controlled/adverse effects , Anesthetics/pharmacology , Female , Humans , Labor, Obstetric , Pregnancy
3.
Article in Chinese | WPRIM | ID: wpr-928700

ABSTRACT

OBJECTIVE@#To investigate the role of relationship between the expression of miRNA181a-5p and imbalance of Treg/Th17 in the pathogenesis of primary immune thrombocytopenia(ITP), which contributes to clarify the mechanism of T cell immune imbalance in ITP patients.@*METHODS@#Peripheral blood was collected from 37 ITP patients, concluding 21 untreated patients and 16 effectively treated patients, and 19 healthy controls; Peripheral blood mononuclear cells (PBMC) were isolated and the expression of miRNA181a-5p and Notch1 was analyzed by RT-PCR. The proportion of Th17 subsets and Treg cells in the peripheral circulation was detected by flow cytometer (FCM). Clinical data of ITP group was collected, including age, platelet count and disease course.@*RESULTS@#The expression of miR-181a-5p was significantly decreased in ITP group than that of healthy control group (P<0.01). After effective treatment, the expression of miR-181a-5p was significantly higher than that of ITP group (P<0.05), but still significantly lower than that of healthy control group (P<0.01); The expression of Notch1 was significantly increased in ITP group and effectively treated group than that of healthy control group (P<0.01). There was no significant difference in proportion of Treg cells in ITP group, effectively treated group and healthy control group (P>0.05). The proportion of Th17 subsets in ITP group was significantly increased than that of healthy control group (P<0.05), while the ratio of Treg/Th17 was significantly decreased (P<0.05). There was a positive correlation between the expression of miR-181a-5p and ratio of Treg/Th17 in ITP group (r=0.555).@*CONCLUSION@#The expression of miR-181a-5p is significantly decreased in ITP patients, which is closely related to the imbalance of Treg/Th17 cells. After effective treatment, the expression of miR-181a-5p can be significantly corrected, but still failed to reach the level of healthy people. While the expression of Notch1 is significantly increased in ITP patients, and could not reach the level of healthy people after effective treatment.


Subject(s)
Humans , Leukocytes, Mononuclear , Platelet Count , Purpura, Thrombocytopenic, Idiopathic , T-Lymphocytes, Regulatory , Th17 Cells
4.
Article in Chinese | WPRIM | ID: wpr-928640

ABSTRACT

OBJECTIVES@#To study the features of intestinal flora in children with food protein-induced proctocolitis (FPIP) by high-throughput sequencing.@*METHODS@#A total of 31 children, aged <6 months, who experienced FPIP after exclusive breastfeeding and attended the outpatient service of the Third Affiliated Hospital of Zunyi Medical University from October 2018 to February 2021 were enrolled as the FPIP group. Thirty-one healthy infants were enrolled as the control group. Fecal samples were collected to extract DNA for PCR amplification. High-throughput sequencing was used to perform a bioinformatics analysis of 16S rDNA V3-V4 fragments in fecal samples.@*RESULTS@#The diversity analysis of intestinal flora showed that compared with the control group, the FPIP group had a lower Shannon index for diversity (P>0.05) and a significantly higher Chao index for abundance (P<0.01). At the phylum level, the intestinal flora in both groups were composed of Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Compared with the control group, the FPIP group had a significant reduction in the composition ratio of Actinobacteria (P<0.001) and a significant increase in the composition ratio of Proteobacteria (P<0.05). At the genus level, the intestinal flora in the FPIP group were mainly composed of Escherichia, Clostridium, Enterococcus, Klebsiella, and Bifidobacterium, and the intestinal flora in the control group were mainly composed of Bifidobacterium and Streptococcus. Compared with the control group, the FPIP group had a significant reduction in the composition ratio of Bifidobacterium and Ruminococcus (P<0.05) and significant increases in the composition ratios of Clostridium and Shigella (P<0.05).@*CONCLUSIONS@#Compared with the control group, the FPIP group has a reduction in the diversity of intestinal flora and an increase in their abundance, and there are certain differences in several bacterial genera. These results suggest that changes in the composition of intestinal flora at genus level may play an important role in the development and progression of FPIP.


Subject(s)
Bacteria/genetics , Bifidobacterium/genetics , Child , Gastrointestinal Microbiome , High-Throughput Nucleotide Sequencing/methods , Humans , Infant , Proctocolitis , RNA, Ribosomal, 16S/genetics
5.
Article in English | WPRIM | ID: wpr-928593

ABSTRACT

OBJECTIVES@#To study the risk factors for postoperative delirium (POD) in children with congenital heart disease.@*METHODS@#A prospective nested case-control study was performed on children with congenital heart disease who underwent surgery in Fuwai Hospital, Chinese Academy of Medical Sciences, from December 2020 to June 2021. The clinical data were compared between the POD group (n=114) and non-POD group (n=102). A multivariate unconditional logistic regression analysis was used to investigate the risk factors for POD in children with congenital heart disease.@*RESULTS@#The multivariate logistic regression analysis showed that age (OR=0.951, P<0.001), gender (OR=2.127, P=0.049), number of invasive catheters per day (OR=1.490, P=0.017), degree of postoperative pain (OR=5.856, P<0.001), and preoperative parental anxiety level (OR=1.025, P=0.010) were independent risk factors for POD in children with congenital heart disease.@*CONCLUSIONS@#The risk of POD increases in children with congenital heart disease who are younger, male, have higher number of invasive catheters per day, higher degree of postoperative pain, or higher preoperative parental anxiety level.


Subject(s)
Case-Control Studies , Child , Delirium/complications , Heart Defects, Congenital/surgery , Humans , Male , Postoperative Complications/etiology , Prospective Studies , Risk Factors
6.
Article in English | WPRIM | ID: wpr-928586

ABSTRACT

OBJECTIVES@#To study the serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in children with autism spectrum disorder (ASD) and their association with the core symptoms of ASD.@*METHODS@#A total of 150 ASD children aged 2-7 years (ASD group) and 165 healthy children matched for age and sex (control group) who were recruited at the outpatient service of Chongqing Health Center for Women and Children were enrolled as subjects. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the core symptoms of the ASD children. Chemiluminescence was used to measure the serum levels of IGF-1 and IGFBP-3 in both groups.@*RESULTS@#The ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). The children with severe ASD had significantly lower serum levels of IGF-1 and IGFBP-3 than those with mild-to-moderate ASD (P<0.001). For the children aged 2-3 years, the ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). Boys had a significantly lower serum level of IGF-1 than girls in both ASD and control groups (P<0.05). The serum levels of IGF-1 and IGFBP-3 were negatively correlated with the total score of CARS (r=-0.32 and -0.40 respectively, P<0.001).@*CONCLUSIONS@#The reduction in serum IGF-1 level in early childhood may be associated with the development of ASD, and the serum levels of IGF-1 and IGFBP-3 are associated with the core symptoms of ASD children.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Child, Preschool , Female , Humans , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor I , Male
7.
Article in Chinese | WPRIM | ID: wpr-928233

ABSTRACT

In existing vascular interventional surgical robots, it is difficult to accurately detect the delivery force of the catheter/guidewire at the slave side. Aiming to solve this problem, a real-time force detection system was designed for vascular interventional surgical (VIS) robots based on catheter push force. Firstly, the transfer process of catheter operating forces in the slave end of the interventional robot was analyzed and modeled, and the design principle of the catheter operating force detection system was obtained. Secondly, based on the principle of stress and strain, a torque sensor was designed and integrated into the internal transmission shaft of the slave end of the interventional robot, and a data acquisition and processing system was established. Thirdly, an ATI high-precision torque sensor was used to build the experimental platform, and the designed sensor was tested and calibrated. Finally, sensor test experiments under ideal static/dynamic conditions and simulated catheter delivery tests based on actual human computed tomography (CT) data and vascular model were carried out. The results showed that the average relative detection error of the designed sensor system was 1.26% under ideal static conditions and 1.38% under ideal dynamic stability conditions. The system can detect on-line catheter operation force at high precision, which is of great significance towards improving patient safety in interventional robotic surgery.


Subject(s)
Catheters , Equipment Design , Humans , Mechanical Phenomena , Robotic Surgical Procedures/methods , Robotics
8.
Article in Chinese | WPRIM | ID: wpr-928018

ABSTRACT

This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1β(IL-1β) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.


Subject(s)
Animals , Diabetes Mellitus, Type 2/drug therapy , Gastrointestinal Microbiome , Inflammation/drug therapy , Insulin , Powders , Rats
9.
China Pharmacy ; (12): 1075-1081, 2022.
Article in Chinese | WPRIM | ID: wpr-923755

ABSTRACT

OBJECTIVE To prepare Gambogic acid (GA) nanocapsules (GA-LNCs) and Neogambogic acid (NGA) nanocapsules(NGA-LNCs),and to evaluate their antidiabetic activities. METHODS Using water as the aqueous phase ,medium- chain triglyceride as the oil phase and polyethylene glycol monostearate as the surfactant ,GA-LNCs and NGA-LNCs were prepared by phase inversion method. Using entrapment efficiency and drug-loading amount as index ,the formulation technologies of above 2 nanocapsules were optimized by simplex lattice design. Its physical and chemical properties were investigated. The diabetic mice model was established. GA-LNCs and NGA-LNCs (1.92 and 2.42 mg/kg respectively )were given intragastrically ,once a day ,for consecutive 6 weeks. The fasting blood glucose of mice ,the activities of superoxide dismutase (SOD)and glutathione peroxidase (GSH-Px),the contents of malondialdehyde (MDA),total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol (LDL-C)were all detected. RESULTS The optimal formulation of 2 kinds of nanocapsules included 60% water,10% medium-chain triglyceride ,30% polyethylene glycol monostearate (total amount of the three was 2 g)and 35 mg GA or NGA . The encapsulation efficiencies of GA-LNCs and NGA-LNC obtained by the optimal formulation were (92.01±0.68)% and(93.12±2.11)%;the drug-loading amount were (0.99±0.21)% and(1.21±0.22)%, respectively. GA-LNCs and NGA-LNCs were yellow ,homogeneous and transparent liquid without precipitation. They were spherical in microscopic shape , and had obvious shell- Δ 基金项目:吉林省科技发展计划项目(No.20200404090YY);吉 membrane structure. The particle sizes were (28.11 ± 9.76) 林省教育厅科学技术研究项目(No.JJKH20210372KJ) *硕士研究生 。研究方向 :植物药 。E-mail:zhanhe0108@163. and(22.06±6.84)nm;Zeta potential were (-4.09±1.00) com and(-17.40±1.32)mV,and polydispersity were 0.93±0.06 # 通信作者:讲师,博士。研究方向:中药有效成分治疗疾病的作 and 0.74±0.12. The results of animal experiments showed that 用机制。E-mail:chenweijia_jlau@163.com both GA-LNCs and NGA-LNCs could sig nificantly increase 中国药房 2022年第33卷第9期 China Pharmacy 2022Vol. 33 No. 9 ·1075· the activities of SOD and GSH-Px and the seru m content of HDL-C (P<0.05 or P<0.01)in model mice ,and significantly decreased the fasting blood glucose and the serum contents of MDA , TC, TG and LDL-C (P<0.05 or P<0.01). CONCLUSIONS GA-LNCs,NGA-LNCs prepared in this study are good in physical and chemical properties and have good anti-diabetes activity.

10.
Article in Chinese | WPRIM | ID: wpr-923489

ABSTRACT

@#As a structural barrier between the brain and the systemic circulation, the blood-brain barrier prevents macromolecules and most small-molecule drugs from entering the brain, which make it difficuct to treat central diseases.Various solute carriers such as glucose transporters and amino acid transporters which can transport various nutrients into the brain, are highly expressed on the blood-brain barrier.The ligand corresponding to the transporter is modified on the nano-drug carrier, and the drug is carried across the blood-brain barrier through transporter-mediated transport, which can achieve high-efficiency delivery of drugs to the brain and improve the diagnostic sensitivity and therapeutic effect of central diseases.In this paper, we review different types of solute carriers to mediate nanoformulations such as liposomes, metal nanoparticles, polymer micelles and dendrimers across the blood-brain barrier for the treatment of brain diseases and discuss the opportunities and challenges of this strategy in future applications.

11.
Acta Pharmaceutica Sinica ; (12): 492-499, 2022.
Article in Chinese | WPRIM | ID: wpr-922915

ABSTRACT

A novel sort of nano-component was extricated and isolated from Descurainiae Semen Carbonisatum (DSC), and its hemostatic component was considered through pharmacological experiments. A muffle furnace was used to prepare DSC at 250 ℃, 300 ℃ and 350 ℃, and the DSC dialysate at each temperature was obtained by the extraction and separation method. Low-resolution transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM) were utilized to characterize the nano-components. Ultraviolet spectroscopy (UV-Vis), fluorescence spectroscopy (FL) and infrared spectroscopy (FTIR) were utilized to measure its optical characteristics and functional group information. The anti-hemorrhagic effects were evaluated by liver bleeding tests and the related hemostatic mechanisms of the obtained nano-components were further assessed by detecting blood coagulation and PLT quantity to discuss the hemostasis mechanism. The experiments complied with the Animal Ethics Committee of Beijing University of Chinese Medicine. TEM results showed that there was a novel type of nano-component in the DSC dialysate bag, which was named DSC nano-components (DSC-NCs). The experimental results of liver bleeding in mice showed that DSC-NCs prepared at 250 ℃, 300 ℃, and 350 ℃ could reduce the bleeding time of mice liver. Among them, DSC-NCs prepared at 350 °C had the best effect. In addition, DSC-NCs prepared at various temperatures can also reduce the prothrombin time (PT) value, increase the fibrinogen (FIB) value and the platelet (PLT) value to varying degrees. DSC-NCs have a certain hemostatic effect, which may be related to the activation of the exogenous coagulation system, the increase of FIB value and the increase of platelet content. This provides a new research direction for exploring the treatment of bleeding diseases, and provides a new perspective for the potential application of DSC-NCs in the medical field.

12.
Chinese Journal of Biotechnology ; (12): 418-428, 2021.
Article in Chinese | WPRIM | ID: wpr-878572

ABSTRACT

As an extremely important organelle in eukaryotic cells, endoplasmic reticulum (ER) plays a key role in the synthesis and processing of biomacromolecules, material transport, ion homeostasis maintenance, signal transduction, exchange of materials and signals between organelles. Many important human diseases, such as cancers, autoimmune diseases, pathogenic infections, neurodegenerative diseases and diabetes, are closely related to ER dysfunction. With the development of nanotechnology, the exploration and application of ER-targeted nanodrugs gradually become a research hotspot in the field of nanomedicine, bioengineering, material chemistry and other fields. In this paper, the relationship between ER dysfunction and disease occurrence, the principle of designing ER-targeted nanodrugs and their biomedical application are reviewed. ER-targeted nanodrugs are designed based on nanodrug carriers or self-assembly of bioactive molecules. These nanodrugs could target the ER in an active or passive manner and function by disrupting or maintaining the ER functions. The ER-targeting nanodrugs have a wide application prospect in cancer therapy, immune regulation, nervous system repairment, and so on.


Subject(s)
Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Homeostasis , Humans , Neoplasms/drug therapy , Signal Transduction
13.
Chinese Medical Journal ; (24): 1324-1328, 2021.
Article in English | WPRIM | ID: wpr-878163

ABSTRACT

BACKGROUND@#There have been few real-life dose-comparing studies on the efficacy and safety of secukinumab in Chinese patients with plaque psoriasis. We conducted a real-life cohort study to investigate the efficacy and safety of secukinumab 150 and 300 mg in Chinese patients with moderate-to-severe plaque psoriasis.@*METHODS@#A total of 106 patients with moderate-to-severe plaque psoriasis were included in this study. Patients received either secukinumab 150 mg or secukinumab 300 mg according to patients' weights and severity of psoriasis. The treatment continued for at least 24 weeks. The efficacy was evaluated by improvement in the psoriasis area and severity index (PASI) scores. The safety was also analyzed.@*RESULTS@#Fifty-nine patients (55.7%) were treated with secukinumab 300 mg and 47 patients (44.3%) were treated with secukinumab 150 mg. After 12-week treatment, PASI75/90/100 responses were achieved in 100%, 97.8%, and 95.7% of patients, respectively, in secukinumab 150 mg group, and the efficacy was maintained to week 24. In secukinumab 300 mg group, PASI75/90/100 responses were achieved in 93.2%, 81.4%, and 76.3% of patients, respectively, at week 12. In this group, PASI75/90/100 responses reached 91.5%, 86.4%, and 79.9%, respectively, at week 24. Biologic-experienced patients had lower responses than biologic-naïve patients. Secukinumab 150 and 300 mg were well tolerated. Five patients discontinued treatment due to poor response, adverse event, or economic reasons.@*CONCLUSIONS@#This real-life study demonstrated that high PASI 90 and PASI 100 responses were achieved in Chinese psoriasis patients receiving secukinumab 150 or 300 mg. Biologic-naïve was associated with better clinical efficacy.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , China , Cohort Studies , Humans , Psoriasis/drug therapy , Severity of Illness Index , Treatment Outcome
14.
Chinese Medical Journal ; (24): 1310-1316, 2021.
Article in English | WPRIM | ID: wpr-878104

ABSTRACT

BACKGROUND@#Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients.@*METHODS@#A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips.@*RESULTS@#In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients.@*CONCLUSION@#Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.


Subject(s)
DNA Methylation/genetics , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Humans , Leukocytes, Mononuclear , Monocytes , Sjogren's Syndrome/genetics
15.
Article in Chinese | WPRIM | ID: wpr-861655

ABSTRACT

Objective: To investigate the efficacy and safety of paclitaxel combined with apatinib in comparison with paclitaxel alone as the second-line treatment for gastric cancer. Methods: Patients with advanced gastric cancer who had been treated at Chifeng Municipal Hospital, Chifeng Clinical Medical School of inner Mongolia Medical University, from March 2017 to March 2018 were enrolled. Inclusion criteria were human epidermal growth factor receptor-2(HER-2)-negative cancer and progression after the first-line treatment with fluorouracil combined with platinum. Patients were divided into groups administered with a single drug and combination of drugs. The single-drug group was administered with paclitaxel chemotherapy, while the combined-drug group with the paclitaxel combined with apatinib treatment. In both groups, the primary endpoint of observation was progression-free survival (PFS), while the secondary endpoint was the disease control rate (DCR), overall response rate (ORR), and safety. Results: A total of 60 patients were enrolled, including 30 patients in each of single- and combined-drug groups. PFS was significantly better in the combined-drug group than in the single-drug group (P0.05). The incidence of hypertension was significantly higher in the combined-drug group than in the single-drug group (P0.05). Conclusions: Paclitaxel combined with apatinib mesylate is superior to paclitaxel alone in the second-line treatment of gastric cancer. PFS, DCR, and ORR are superior with paclitaxel combined with apatinib mesylate than with paclitaxel alone. Although DCR and ORR in the combined-drug group were not significantly different from those in the single-drug group, the PFS was significantly longer in the combined-drug group, and the toxic and side effects of paclitaxel combined with apatinib mesylate were tolerable and safe.

16.
Acta Pharmaceutica Sinica B ; (6): 181-202, 2021.
Article in English | WPRIM | ID: wpr-881132

ABSTRACT

Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,

17.
Article in English | WPRIM | ID: wpr-875497

ABSTRACT

Background/Aims@#Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. @*Methods@#Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. @*Results@#LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. @*Conclusions@#LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

18.
Article in English | WPRIM | ID: wpr-875154

ABSTRACT

Background@#Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. @*Objectives@#In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. @*Methods@#In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. @*Results@#At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. @*Conclusions@#The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

19.
Article in English | WPRIM | ID: wpr-874370

ABSTRACT

Purpose@#Tumor regression grade (TRG) has been widely used in gastrointestinal carcinoma to assess pathological responses to neoadjuvant chemotherapy (NCT). There are various standards without a consensus, and it is still unclear which kind of system has better predictive value. This study aims to investigate and compare the predictive ability of the Mandard and Becker TRGs in patients with locally advanced gastric cancer. @*Materials and Methods@#A total of 290 patients with locally advanced gastric adenocarcinoma who underwent NCT and curative surgery were studied. Survival analysis for overall survival (OS) and disease-free survival (DFS) were based on the Kaplan-Meier method and Cox proportional hazards method. Predictive values of TRGs and models were assessed by time-dependent receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), nomogram, and calibration curve. @*Results@#In multivariable analysis, the Mandard TRG was associated with OS (hazard ratio [HR], 1.806; p=0.026) and DFS (HR, 1.792; p=0.017). The Becker TRG was also related to OS (HR, 1.880; p=0.014) and DFS (HR, 1.919; p=0.006). The Mandard and Becker TRG AUCs for 5-year survival were 0.72 and 0.71, respectively. The whole models showed an increased predictive value, with AUCs of 0.85 and 0.86, respectively. There was no significant difference between the two TRGs and two models. @*Conclusion@#TRG was an independent predictor for survival, and there was no significant difference between these two systems.

20.
Chinese Journal of School Health ; (12): 240-244, 2021.
Article in Chinese | WPRIM | ID: wpr-873648

ABSTRACT

Objective@#To analyze the possible responses of parents of young children to Child sexual assault (CSA) and the potential influencing factors, so as to provide evidence for prevention programs of CSA.@*Methods@#Part of the data from "2016-2020 Child Injury Prevention Project" was used to analyze responses to CSA among parents of children younger than 3rd grade in primary school by chi square test and Logistic regression analysis.@*Results@#A total of 4 072 parents were included in the analysis. Among them, 86.8% of parents chose "to solve problems together", 51.0% of parents taking children to a "psychologist", 4.9% of parents "scolding children for being too careless", 2.9% of parents "letting child not disclose abuse" and 6.5% of parents chose "other" coping methods. Parents with foreign nationality [OR(95%CI)=2.58(1.25-5.15)] and lower education level (OR=0.26-0.64) tend to "blame" their children. Mothers [(OR(95%CI)=0.54(0.33-0.90)], higher parental education level (OR=0.27-0.72) were more reluctant to encourage their children to keep quiet. Mothers [OR(95%CI)=1.73(1.32-2.27)], older children (OR=1.33-1.78) and parents with higher education level (OR=1.65-2.99) tend to "accompany". Parents aged 30 or more, and from high school/technical school/technical secondary school tend to take their children to see a "psychologist" [OR(95%CI)=1.39(1.14-1.71), 1.79(1.26-2.53)].@*Conclusion@#Parents universally pay attention to the physical and mental health of children after CSA, but some parents still take negative coping methods, e.g. "blame" and "not disclose". Parenting educational level, duration of parent-child communication and age of children are primary factors associated with parental responses to child sexual assault. This study suggests that prevention secondary injury following child sexual assault should be farther strengthened, while fully considering the characteristics of the educated objects.

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