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1.
Acta Pharmaceutica Sinica ; (12): 201-207, 2021.
Article in Chinese | WPRIM | ID: wpr-872599

ABSTRACT

The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.

2.
Frontiers of Medicine ; (4): 704-717, 2021.
Article in English | WPRIM | ID: wpr-922499

ABSTRACT

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.


Subject(s)
COVID-19 , Humans , Medicine, Chinese Traditional , Research , SARS-CoV-2 , Treatment Outcome
3.
Article in Chinese | WPRIM | ID: wpr-907441

ABSTRACT

In the face of DNA damage caused by various factors, cells have a set of response and repair mechanisms. Cell cycle arrest plays an important role in the DNA damage repair, which provides enough time for repairing damaged DNA. Research on cell cycle regulation focuses on cyclin-dependent protein kinases (CDKs) and cell cycle checkpoints. In the process of DNA damage repair, phosphatidylinositol-3-kinase like kinases (PIKKs) which are recruited to the DNA damage sites can activate cell cycle checkpoint-related proteins to halt cell cycle. In the common DNA damage repair pathways, such as base excision repair (BER), nucleotide excision repair (NER) , mismatch repair (MMR) , and DNA double-strand break repair, the recruitment of repair-related proteins also plays a role in the cell cycle regulation. In this paper, the relationship between the main forms of DNA damage repair and cell cycle arrest and relevant research progress were reviewed.

4.
Article in Chinese | WPRIM | ID: wpr-906602

ABSTRACT

@#Objective    Zero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events. Methods    We conducted a survey of systematic reviews published in two periods: January 1, 2015 to January 1, 2020 and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews. Results    We included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant [proportion difference=–0.09, 95%CI (–0.21, 0.03), P=0.12]. Conclusion    Systematic review authors routinely treated studies with zero-events in both arms as "non-informative" carriers and excluded them from their reviews. Whether studies with no events are "informative" or not, largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.

5.
International Eye Science ; (12): 253-256, 2021.
Article in Chinese | WPRIM | ID: wpr-862421

ABSTRACT

@#Dry eye has become one of the relatively common complications following keratoplasty due to the surgical destruction of the ocular surface and long-term application of topical eye drops. Dry eye will result in corneal epithelial defects and further could decrease the survival rate of the grafts. In order to better understand dry eye following corneal transplantation and to provide clinical guidance for physicians, we reviewed recent domestic and international published literatures regarding its pathogenesis, clinical features, prevention and management.

6.
Article in Chinese | WPRIM | ID: wpr-872222

ABSTRACT

Objective:To explore the influencing factors of 31-day unplanned readmission in obstetrics.Methods:The medical records and relevant clinical data of 29 public hospitals in a province in 2017 were collected to construct a two-level logistic regression model on the influencing factors of 31-day unplanned readmission.Results:In 2017, there were 71 330 obstetric patients discharged from 29 public hospitals, 690 of whom were unplanned readmitted in 31 days, accounting for 0.97%. The type of medical insurance payment, number of previous hospitalization, condition of previous hospitalization, age, history of cesarean section, pregnancy complications and complications during delivery were all the factors influencing the 31-day unplanned readmission of obstetrics.Conclusions:The condition of 31-day unplanned readmission could be influenced by the factors of sociology, previous visit and clinical. These factors should be considered reasonably in the evaluation and management of obstetric quality.

7.
Article in Chinese | WPRIM | ID: wpr-872215

ABSTRACT

Objective:To explore the relationship between death indicators and unplanned return indicators on healthcare quality evaluation.Methods:A total of 836 976 medical record data were collected from 31 tertiary public general hospitals in a diagnosis-related groups(DRG) data platform in 2017. Multiple death indices(low and low-risk risk group mortality, high-risk group mortality, crude mortality, and risk adjusted mortality) and unplanned return indices(31-day unplanned readmission rate and 31-day unplanned return to surgery rate) were calculated. Pearson′s correlation coefficient was used to examine the relationships among those indices.Results:Death indicators were correlated with each other, but the unplanned readmission rate was not correlated with the unplanned reoperation rate( r=0.305). There was no correlation between unplanned re-entry rate and death rate. The correlation coefficients were as follows: unplanned readmission rate versus low and low-risk group mortality( r=-0.227), versus high-risk group mortality( r=-0.098), versus actual mortality( r=-0.130), versus risk adjusted mortality( r=0.010); unplanned reoperation rate versus low and low-risk group mortality( r=0.105), versus high-risk group mortality( r=0.030), versus actual mortality( r=-0.004), versus risk adjusted mortality( r=-0.141). Conclusions:The indicators of death and the indicators of unplanned return are not the same in terms of actual management technology and evaluation effect. They are complementary to each other and can form an ideal combination of quality evaluation indicators.

8.
Article in Chinese | WPRIM | ID: wpr-870189

ABSTRACT

Objective:To investigate the value of programmed death-1(PD-1) expression on the T lymphocytes for the prognosis of septic patients.Methods:From September 2017 to May 2019, septic patients were included in Department of Intensive Care Unit at 6 hospitals. The PD-1 expression on T cells were measured by flow cytometry. Logistic regression was conducted to analyze independent risk factors related to death within 28 days,and receiver operating characteristic curve(ROC) was conducted to evaluate the prognostic value of PD-1 expression on T cells in septic patients.Results:A total of 64 septic patients were enrolled to this study,including 32 survivors and 32 deaths. The PD-1 expression on T cells in the death group was significantly higher than that in the surviving group ( P<0.05). Correlation analysis showed that the percentages of PD-1 +/CD3 +T cells and PD-1 +/CD8 +T cells were positively correlated with procalciton in ( r=0.313, P =0.015; r=0.375, P=0.003), logistic regression analysis showed that the percentages of PD-1 +/CD3 +,PD-1 +/CD4 +,PD-1 +/CD8 +T cells were independent risk factors for the death of sepsis patients. The percentage of PD-1 +/CD3 +T cell was 3.63%, with AUC 0.842, sensitivity to predict the mortality 96.43% and specificity 59.38%, ( P<0.000 1). The percentage of PD-1 +/CD4 +T cell was 4.65%, with AUC 0.847, sensitivity 96.43%, specificity 62.50%,( P<0.000 1). The percentage of PD-1 +/CD8 +T cell was 3.91%, with AUC 0.771, sensitivity 64.29%, specificity 81.25%,( P=0.000 3). Conclusions:The T cell PD-1 expression is an independent risk factor to predict the 28-day mortality in septic patients. Combining the proportions of PD-1 +/CD3 +, PD-1 +/CD4 +and PD-1 +/CD8 +T cells may further enhance the predictive value for death.

9.
Journal of Chinese Physician ; (12): 1497-1500,1504, 2020.
Article in Chinese | WPRIM | ID: wpr-867428

ABSTRACT

Objective:To investigate the difference of vitamin A and E levels in children with different respiratory diseases at different ages.Methods:A total of 671 children in Hunan Children's Hospital from July 2017 to October 2019 were selected as the disease group, including 197 cases of pneumonia, 152 cases of recurrent respiratory tract infection, 91 cases of asthma, 88 cases of cough variant asthma and 143 cases of Mycoplasma pneumoniae pneumonia; At the same time, 245 healthy children were selected as the normal group. The serum vitamin A and vitamin E levels of the two groups were detected by high performance liquid chromatography (HPLC).Results:⑴ The vitamin A level [(0.31±0.09)mg/L] of the disease group was lower than the normal group [(0.35±0.25)mg/L], and the vitamin E level [(8.92±2.57)mg/L] was lower than the normal group [(9.62±2.79)mg/L], with statistically significant difference ( P<0.05); ⑵ The level of vitamin A in the disease group at the age of >1-3 years [(0.32±0.09)mg/L] was lower than that in the normal group of the same age group [(0.35±0.08)mg/L]; the level of vitamin A in the disease group at the age of >3-6 years old [(0.30±0.08)mg/L] was lower than that of the same age group [(0.32±0.07)mg/L], with statistically significant difference ( P<0.05); ⑶ The vitamin E level of the disease group at >1-3 years old [(9.23±2.56)mg/L], >3-6 [(8.02±1.86)mg/L] and >6-14 years old [(8.02±1.82)mg/L] were lower than that of the same age normal group [(9.76±2.81)mg/L, (9.67±2.87)mg/L, (9.19±2.58)mg/L], with statistically significant difference ( P<0.05); ⑷ There were significant differences in vitamin A levels among different age in disease group ( P<0.05). Among them, the children with high risk of subclinical deficiency accounted for the largest proportion (45.78%) in the 6-month-1-year-old group, and the proportion of children with normal vitamin A levels in other age groups was the largest; ⑸ There are significant differences in vitamin E levels in different age groups in the disease group ( P<0.05), the levels in the normal range accounts for the largest proportion of all ages; ⑹ The levels of vitamin A and vitamin E in mycoplasma pneumoniae infection group were increased compared with in recurrent respiratory infection group , asthma group, and cough variant asthma group, and the difference was statistically significant ( P<0.05). Compared with the pneumonia group, the level of vitamin E increased in the recurrent respiratory infection group, and the difference was statistically significant ( P<0.05); The vitamin E levels in the cough variant asthma group were reduced compared with the repeated respiratory infection group, asthma group and pneumonia group ( P<0.05). Conclusions:The Vitamin A and E levels of children suffering from respiratory diseases are lower than those of normal children. The Vitamin A and E levels of different respiratory diseases and different age groups are different. Vitamin A and E supplementation may be significantly targeted according to different ages and different respiratory diseases in clinical practice.

10.
Journal of Chinese Physician ; (12): 43-45,49, 2020.
Article in Chinese | WPRIM | ID: wpr-867201

ABSTRACT

Objective To explore the association between Vitamin A,E and mycoplasma pneumoniae pneumonia in children.Methods 153 children with mycoplasma pneumoniae pneumonia and 653 health children were selected as cases and controls,respectively.Propensity score matching (PSM) analysis were conducted to reducing confounding bias between groups.Blood samples were collected to test serum levels of vitamin A and E using high performance liquid chromatography (HPLC).Logistic regression was implemented to determine odds ratios (OR) and 95% confidence intervals (CI) for evaluating the association of mycoplasma pneumoniae pneumonia with the serum levels of Vitamin A and E.Results Mter propensity score matching,the study cohort included 153 cases with mycoplasma pneumoniae pneumonia and 306 health children as controls.Before matching,with age and gender adjusted,logistic regression analysis indicated that higher serum levels of Vitamin A and E led to a lower risk of mycoplasma pneumoniae pneumonia (OR =0.075,95% CI:0.007-0.815;OR =0.854,95% CI:0.792-0.986).After matching,higher serum level of Vitamin E had a significantly lower risk of mycoplasma pneumoniae pneumonia (OR =0.877,95% CI:0.810-0.950).Conclusions The serum levels of Vitamin A didnt have a statistically significant association with mycoplasma pneumoniae pneumonia.However,we observed an obvious association between Vitamin E and mycoplasma pneumoniae pneumonia.Hence Vitamin E clinical monitoring and supplementation are vital for preventing and treating mycoplasma pneumoniae pneumonia.

11.
Article in Chinese | WPRIM | ID: wpr-828410

ABSTRACT

Myricetin and its glycosides are important flavonols commonly found in plants, and they are natural organic compounds with diverse pharmacological activities. Numerous studies have demonstrated that myricetin and its glycosides are strong antioxidants that have great potential in preventing, alleviating and assisting the treatment of chronic non-infectious diseases such as cancer, diabetes, and cardiovascular diseases. In addition, myricetin and its glycosides also have antiviral, antibacterial, anti-inflammatory, analgesic, liver protection and other pharmacological activities. Myricetin contains more hydroxyl groups in the parent ring structure than other flavonoids, so myricetin and its glycosides have stronger pharmacological activities than other flavonols or flavonoids such as quercetin and kaempferol. Therefore, myricetin and its glycosides have great development and application prospects. In this paper, the classification and distribution of myricetin and its glycosides, their pharmacological activity and mechanism, as well as comparison with other flavonoids were reviewed. In addition, limitations of the current research and application of myricetin and its glycosides were analyzed, and the further studies on pharmacological activities as well as their dose-activity relationship, structure-activity relationship, chemical modification, biosynthesis and application prospects of myricetin and its glycosides were discussed and proposed.


Subject(s)
Flavonoids , Flavonols , Glycosides , Quercetin
12.
Article in Chinese | WPRIM | ID: wpr-828669

ABSTRACT

OBJECTIVE@#To study the moderated mediation for attention deficit/hyperactivity disorder (ADHD) with the symptoms of anxiety in children.@*METHODS@#A total of 12 271 students were included with an average age of 8.9±1.9 years, including 6 743 male students and 5 508 female students, and 20 students with missing data on gender. Child psychological trauma questionnaires (parents version) and Conners questionnaires (parent version) were completed by the parents of primary school students. The data was studied by univariate analysis, multivariate analysis and moderated mediation analysis.@*RESULTS@#The results of the univariate analysis showed that in all subjects, boys, and girls, the scores of hyperactivity index and childhood trauma were positively correlated with the score of anxiety (P<0.01), and ADHD and childhood trauma positively predicted anxiety disorder (P<0.001). The results of the multivariate analysis showed that in all subjects, boys, and girls, the scores of hyperactivity index (ADHD symptoms) and childhood trauma positively predicted the score of anxiety (P<0.001), and both ADHD and childhood trauma positively predicted anxiety disorder (P<0.001). The results of the moderated mediation analysis showed that childhood trauma was a mediating factor for the relationship between hyperactivity index and anxiety index in boys and girls (P<0.05), and sex moderated the relationship between hyperactivity index and anxiety index (P<0.001).@*CONCLUSIONS@#ADHD symptoms/ADHD are closely associated with anxiety symptoms/anxiety disorder. Childhood trauma exerts a mediating effect on the relationship between ADHD symptoms and anxiety symptoms, and sex moderates the relationship between ADHD symptoms and anxiety symptoms.


Subject(s)
Anxiety , Anxiety Disorders , Attention Deficit Disorder with Hyperactivity , Child , Child Behavior Disorders , Female , Humans , Male , Surveys and Questionnaires
13.
Article in English | WPRIM | ID: wpr-826616

ABSTRACT

This study was conducted to reveal the effects of silicon (Si) application on nutrient utilization efficiency by rice and on soil nutrient availability and soil microorganisms in a hybrid rice double-cropping planting system. A series of field experiments were conducted during 2017 and 2018. The results showed that Si nutrient supply improved grain yield and the utilization rates of nitrogen (N) and phosphorus (P) to an appropriate level for both early and late plantings, reaching a maximum at 23.4 kg/ha Si. The same trends were found for the ratios of available N (AN) to total N (TN) and available P (AP) to total P (TP), the soil microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), microbial biomass phosphorus (MBP), and the ratios of MBN to TN and MBP to TP, at different levels of Si. Statistical analysis further revealed that Si application enhanced rice growth and increased the utilization rate of fertilizer due to an ecological mechanism, i.e., Si supply significantly increased the total amount of soil microorganisms in paddy soil compared to the control. This promoted the mineralization of soil nutrients and improved the availability and reserves of easily mineralized organic nutrients.

14.
Acta Pharmaceutica Sinica ; (12): 1965-1970, 2020.
Article in Chinese | WPRIM | ID: wpr-825146

ABSTRACT

Recombinant adeno-associated virus (rAAV)-based vector has shown great promise for human gene therapy, due to its advantage in eliciting long-term transgene expression, absence of adverse effect, infection ability to both dividing and non-dividing cells, non-genomic integration, and low immunotoxity. To date, three AAV-based products have been authorized to enter European and American markets, and more than 200 rAAV-based candidates are in the process of clinic trails. Nevertheless, domestic industry is facing the challenge of manufacturing clinical grade rAAV vector, and regulatory agencies are lack of practical experience in assessing such products. Herein, this paper summarizes the latest research progress of rAAV-based gene therapy products, and discusses some quality assessment concerns in raw materials, manufacturing process and quality control, expecting to promote its clinical transformation and application.

15.
Journal of Chinese Physician ; (12): 43-45,49, 2020.
Article in Chinese | WPRIM | ID: wpr-799133

ABSTRACT

Objective@#To explore the association between Vitamin A, E and mycoplasma pneumoniae pneumonia in children.@*Methods@#153 children with mycoplasma pneumoniae pneumonia and 653 health children were selected as cases and controls, respectively. Propensity score matching (PSM) analysis were conducted to reducing confounding bias between groups. Blood samples were collected to test serum levels of vitamin A and E using high performance liquid chromatography (HPLC). Logistic regression was implemented to determine odds ratios (OR) and 95% confidence intervals (CI) for evaluating the association of mycoplasma pneumoniae pneumonia with the serum levels of Vitamin A and E.@*Results@#After propensity score matching, the study cohort included 153 cases with mycoplasma pneumoniae pneumonia and 306 health children as controls. Before matching, with age and gender adjusted, logistic regression analysis indicated that higher serum levels of Vitamin A and E led to a lower risk of mycoplasma pneumoniae pneumonia (OR=0.075, 95% CI: 0.007-0.815; OR=0.854, 95% CI: 0.792-0.986). After matching, higher serum level of Vitamin E had a significantly lower risk of mycoplasma pneumoniae pneumonia (OR=0.877, 95% CI: 0.810-0.950).@*Conclusions@#The serum levels of Vitamin A didn't have a statistically significant association with mycoplasma pneumoniae pneumonia. However, we observed an obvious association between Vitamin E and mycoplasma pneumoniae pneumonia. Hence Vitamin E clinical monitoring and supplementation are vital for preventing and treating mycoplasma pneumoniae pneumonia.

16.
Article in Chinese | WPRIM | ID: wpr-805086

ABSTRACT

Objective@#To study on the exposure of polychlorinated biphenyl (PCB) contamination and DNA methylation in male employees in an e-waste dismantling area in Tianjin.@*Methods@#In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. A total of 60 subjects (30 in each of the exposed group and the reference group) were included. The peripheral blood (5 ml) of the study subject was collected, and the PCB concentration was detected. Eight independent subjects in the exposed group and the reference group were randomly selected by random number table method to detect the methylation level of the promoter region of all gene loci, and the mRNA transcript levels.@*Results@#The PCB concentration in peripheral blood of the exposed group was higher than that of the reference group, and the difference was statistically significant (allP values <0.001). The methylation levels of the promoter region of the exposed group and the reference group showed obvious clustering, and 994 gene loci had different degrees of methylation. Compared with the reference group, there were 391 hypomethylation sites and 553 hypermethylation sites in the exposed group. The proportion of methylation sites in the high CpG-rich region was 59.2% and 48.1%, respectively. The mRNA level of the hypomethylated gene in the exposed group was higher (FAM131A, HBM), and the transcription level of the hypermethylated gene was lower (CAPN15, NFIC, SHISA5, FGF13, GRAMD1A, CLEC3B, LILRB2, DCAF7). The mRNA transcription levels of 10 genes above in the exposed group and the reference group were statistically significant (all P values <0.001).@*Conclusion@#The PCB concentration of peripheral blood in the exposed population of e-waste is high. PCB exposure changes the methylation level of specific genes and affects the mRNA transcription level of some genes.

17.
Article in Chinese | WPRIM | ID: wpr-805085

ABSTRACT

Objective@#To study on the genomic stability of male workers engaged in e-waste dismantling area in Tianjin.@*Methods@#In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. The exposed group included 146 workers who engaged in e-waste recycling work more than 1 year. The reference group included 121 farmers who never engaged in e-waste recycling work. Questionnaires were used to collect information of all subjects. The semen and peripheral blood were also collected. Trace elements and polychlorinated biphenyl concentration in blood were detected. DNA damage in peripheral blood and sperm was detected, and gene expression was analyzed. DNA damage was assessed using tail DNA% (TDNA%), tail moment (TM) and olive tail moment (OTM) of comet assay.@*Results@#The ages of the exposed group and the reference group were (33.6±12.1) and (33.9±11.9) years old, respectively. The proportions of subjects with exposure time of ≤3, 4-6, ≥7 years were 43% (63 cases), 26% (53 cases) and 21% (30 cases), respectively. The Pb and polychlorinated biphenyl(PCB) concentrations in the exposed group [(90.4±15.3) μg/ml and (101±30) ng/ml, respectively] were higher than those in the reference group [Pb and PCB concentrations were (60.2±8.9) μg/ml, and (2.5±1.4) ng/ml, respectively (both P values <0.05)]. The TDNA%, TM and OTM of peripheral blood and sperm in the exposed group were 5.9%±0.3% and 2.6%±0.90%, 0.93±0.16 and 0.51±0.20, 0.82±0.09 and 0.56±0.07, respectively, which were all higher than those in the reference group [TDNA%, TM and OTM of peripheral blood and sperm were 1.8%±0.2% and 1.9%±0.2%, 0.21±0.04 and 0.32±0.10, 0.19±0.03 and 0.20±0.08, respectively (all P values <0.001)]. The results of gene expression showed that 20 differentially expressed genes, including 13 up-regulated genes and 7 down-regulated genes, were detected in the exposed group compared with the reference group.@*Conclusion@#There are obvious DNA damage and DNA repair gene disorder in male workers of an e-waste dismantling area in Tianjin. The current operation mode brings potential health risks to workers.

18.
Article in Chinese | WPRIM | ID: wpr-857578

ABSTRACT

Lymphocyte activation gene-3 (LAG-3, CD223) is a class of immunosuppressive receptors, mainly expressed on the cell surface of activated T and natural killer (NK) cells. As with programmed death-1 (PD-1), T cell immunoglobulin domain and mucin domain-3 (TIM-3) and other immune check-points, the expression of LAG-3 in activated T cells is upregulated to prevent the occurrence of autoimmune diseases. In the tumor microenvironment, persistent antigenic stimulation can induce T cells to overexpress LAG-3 and other suppressor molecules, causing local immune suppression in the tumor microenvironment. However, the mechanism by which LAG-3 inhibits downstream signals of T-activation or interacts with other immunosuppressive molecules is still unknown. Preliminary clinical data has shown that anti-LAG-3 and anti-PD-1 antibodies possess synergistic effect on the treatment of tumors. Moreover, LAG-3 has different intracellular domains which are completely different from those of any other immunological negative regulatory molecules, suggesting that LAG-3 might have a unique molecular mechanism and prospect of application. Currently, there are at least 7 kinds of antibody drugs targeting LAG-3 and one kind of LAG-3-Fc fusion protein in clinical research, which indicates that anti-LAG-3 targeted drugs have a broad prospect of clinical application.

19.
Article in Chinese | WPRIM | ID: wpr-857577

ABSTRACT

OBJECTIVE To evaluate plasma pharmacokinetics, distribution of target organs, sedative effect and respiratory depression of sufentanil (SFTN), and dexmedetomidine (DEM) in rats, and to explore the potential drug-drug interactions between the two drugs. METHODS  Rats were intravenously injected with SFTN 20.0 μg•kg-1, DEM 25.2 μg•kg-1 and SFTN+DEM (SFTN 20.0 μg•kg-1, DEM 25.2 μg•kg-1), respectively. Plasma samples were taken at different time points (2, 5, 15, 30 min and 1, 2, 4, 6, 8 h) to determine the concentrations of SFTN and DEM using the liquid chromatography-mass spectrometry (LC-MS/MS) quantitative method established in this study. The same method was used to determine the concentrations of SFTN and DEM in plasma and brain samples taken at different time points (5, 15, 30, 60 and 120 min). Pharmacokinetic parameters were obtained by noncompartmental analysis performed using Phoenix WinNonlin 7.0 (Pharsight, California). The duration of drug-induced loss of right reflex (LORR) and respiratory function were also measured using instrument monitoring. RESULTS  An LC-MS/MS method for quantitative analysis of plasma SFTN and DEM was established and validated. The Cmax,;t1/2, and Cl ;of SFTN in SFTN group were (22.2±2.6) ug•L-1, (2.13±0.69) h and (2288±446) mL•h-1•kg-1, respectively, compared with (15.9±9.4) μg•L-1, (1.22±0.13) h and (3565±743) mL•h-1 •kg-1 in SFTN+DEM group. The Cmax, t1/2, and Cl of DEM in DEM group were (14.0±8.9) μg•L-1, (1.21±0.15) h and (4235±752) mL•h-1•kg-1, compared with (9.4±3.5) μg•L-1, (1.08±0.26) h and (4796±744) mL•h-1•kg-1 in SFTN+DEM group. The Cmax ratio of SFTN in brain and plasma of SFTN+DEM group was 0.49, which was 1.3-fold that of SFTN group (0.45). The Cmax ratio of DEM in brain and plasma of SFTN + DEM group was 16.9, which was 12-fold that of DEM group (1.42). The duration of LORR of SFTN, DEM, and SFTN+DEM groups was 370±13, 41±5 and (104±24) min, respectively, and that of SFTN+DEM group was more significantly extended than those in SFTN and DEM groups (P<0.01). Respiratory depression of SFTN+DEM group was not further aggravated compared with SFTN group, but the duration of inhibition was extended (P<0.05, P<0.01). CONCLUSION  The combination of SFTN and DEM can cause drug-drug interactions, which may promote the sedation and prolong the respiratory depression by increasing the exposure level of DEM brain tissue. In clinical application, attention should be paid to the possible drug-drug interactions or adverse reactions caused by the combination of these two drugs.

20.
Article in Chinese | WPRIM | ID: wpr-751605

ABSTRACT

The small ubiquitin-like modified protein (SUMO) is a protein structurally similar to ubiquitin which is involved in post-translational modification of proteins. SUMOylation refers to the process that SUMO molecule covalently binding to the specific lysine site of target proteins through maturation, activation, binding and ligation by ubiquitin-like specific protease 1 (Ulp1), E1 activating enzyme, E2 binding enzyme, and E3 ligase. SUMOylation alters the activity of target proteins, which is involved in the regulation of various cellular functions such as transcriptional regulation, regulation of embryonic development, cellular stress, maintenance of chromatin structure and genomic stability. In recent years, it has been found that SUMOylation modification is also widely involved in DNA damage repair, especially DNA double-strand breaks (DSBs), which are the most serious types of DNA damage. SUMOylation is involved in almost all processes of DSBs repair, so its role in DNA damage repair has become a research hotspot. In this paper, the research progress of the regulation of SUMOylation in DSBs repair was reviewed.

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