Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 218
Filter
1.
Article in Chinese | WPRIM | ID: wpr-939700

ABSTRACT

OBJECTIVE@#To investigate the age distribution of Mongolian patients with cerebral infarction caused by thrombosis and the correlation and consistency between thromboelastography (TEG) and four parameters of coagulation.@*METHODS@#The age distribution of 298 Mongolian patients with cerebral infarction treated in Affiliated Hospital of Inner Mongolia Minzu University from January 2020 to December 2021 and their TEG, four items of routin coagulation and platelet count were analyzed retrospectively. The correlation and consistency of above-mentioned two detection methods were statistically analyzed.@*RESULTS@#The onset age of 298 Mongolian patients with cerebral infarction was mainly 61-70 years old, accounting for 38.3%, followed by 51-60 years old, accounting for 26.8%. The R time detected by TEG was linearly correlated with PT and APTT(r=0.186,r=0.152). K value, MA value and α-Angle measured by TEG was linearly correlated with Fib (r=-0.364,r=0.616,r=0.359), K value, MA value and α-Angle measured by TEG was linearly correlated with Plt (r=0.318,r=0.519,r=0.301). The R time detected by TEG was consistent with PT and APTT, and the Kappa values were 0.252 (P<0.001), 0.336 (P<0.001). K, MA, and α-Angle measured by TEG was consistent with Fib, the Kappa values were 0.265 (P<0.001), 0.289 (P<0.001) and 0.290 (P<0.001), respectively; K、MA and α-Angle measured by TEG was consistent with Plt, the Kappa values were 0.276 (P<0.001), 0.285 (P<0.001) and 0.302 (P<0.001), respectively.@*CONCLUSION@#The onset age of Mongolian patients with cerebral infarction caused by thrombosis is mainly 61-70 years old, followed by 51-60 years old. The onset age shows a younger trend. There is a significant correlation between TEG and coagulation, but the consistency is weak, therefore, the two methods can not be replaced each other.


Subject(s)
Aged , Blood Coagulation , Blood Coagulation Tests/methods , Cerebral Infarction , Humans , Middle Aged , Retrospective Studies , Thrombelastography/methods , Thrombosis
2.
Article in Chinese | WPRIM | ID: wpr-934903

ABSTRACT

@#Objective    To investigate the feasibility and safety of non-intubation anesthesia in thoracic surgery. Methods    From September 2017 to December 2019, 296 patients were operated at department of thoracic surgery in our hospital. There were 167 males and 129 females with an average age of 50.69±12.95 years, ranging from 16 to 76 years. The patients were divided into two groups according to whether they were intubated: 150 patients were in a non-intubation group, including 83 males and 67 females with an average age of 49.91±13.59 years, ranging from 16 to 76 years, and 146 patients were in an intubation group including 84 males and 62 females with an average age of 51.49±12.26 years, ranging from 16 to 74 years. Intraoperative data, postoperative recovery, inflammatory response of the two groups were compared. Results    There was no statistical difference between the two groups in operation time, blood loss, the lowest oxygen saturation or other indicators (P>0.05). But the highest partial pressure of carbon dioxide of the non-intubation group was higher than that of the intubation group (P=0.012). The non-intubation group was superior to the intubation group in postoperative recovery and inflammatory response (P<0.05). Conclusion    The non-intubation anesthesia is safe and maneuverable in thoracic surgery, and it has some advantages in accelerating postoperative rehabilitation.

3.
Article in English | WPRIM | ID: wpr-929263

ABSTRACT

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.


Subject(s)
Animals , Anti-Inflammatory Agents/pharmacology , Cyclooxygenase 2/chemistry , Dinoprostone , Interleukin-6/metabolism , Iridoid Glucosides , Mice , Molecular Docking Simulation , Pyridinolcarbamate
4.
Article in Chinese | WPRIM | ID: wpr-930546

ABSTRACT

Objective:To search, evaluate and integrate the available evidence on pediatric sedation monitoring, and summarize the best evidence.Methods:Up To Date, BMJ Best Practice, Canadian Medical Association Clinical Practice Guidelines (CMA Infobase), Registered Nurses′ Association of Ontario (RNAO), National institute for Health and Care Excellence (NICE), Evidence-Based Medicine, Cochrane Library, Yimaitong, PubMed, Embase, Wanfang Database, CNKI were searched to collect evidence related to the monitoring of pediatric sedation, including clinical decision-making, guidelines, expert consensus, and evidence-related original research. The search time limit was from the establishment of the database to August 2020. The quality of the literature was evaluated by the suitable evaluated tool based on their types. The level and recommedation grade of the evidence were appraised by the suitable tools of JBI.Results:A total of 13 articles were finally included. Twenty best evidences were summarized, including three aspects of monitoring content, monitoring timing, and monitoring tools.Conclusions:The research summarized the best evidence for pediatric sedation monitoring, and provided evidence-based references for clinical practice and standard formulation. Most of the evidence was form foreign resource. It is suggested that clinical departments or institutions should fully consider the clinical situation. At the same time, high-quality randomized controlled trials should be conducted one step further.

5.
Article in English | WPRIM | ID: wpr-874343

ABSTRACT

Purpose@#The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). @*Materials and Methods@#We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics. @*Results@#The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline. @*Conclusion@#sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.

6.
Article in Chinese | WPRIM | ID: wpr-906057

ABSTRACT

Objective:To explore the long-term effect of Zhenzhu Tiaozhi capsule(FTZ) on hemoglobin A1c(HbA1c)in patients with type 2 diabetes mellitus (T2DM) based on real-world data. Method:T2DM patients who were provided with FTZ (FTZ group) and those receiving conventional hypoglycemic drugs (control group) were extracted from the hospital information system (HIS) of the First Affiliated Hospital of Guangdong Pharmaceutical University, followed by propensity score matching (PSM) for balancing the confounding factors between groups. With HbA1c as the efficacy evaluation index, the difference in efficacy between the two groups was compared using <italic>t</italic>-test and <italic>χ</italic><sup>2</sup> test. For repeated measurement data of the same patient, the difference in efficacy and the stability of FTZ against HbA1c were analyzed by generalized estimating equation (GEE). The factors that might affect the efficacy of FTZ against HbA1c were subjected to multivariate linear regression analysis (MLRA), and the subgroup analyses were then conducted after the stratification of relevant factors. Result:There were 46 patients included in the FTZ group and 1 208 patients in the control group. PSM yielded 42 pairs of samples with balanced covariates between groups. As revealed by one-year observation, ① HbA1c in the FTZ group after treatment was 6.51%±1.09%. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. At the same time, the HbA1c compliance rate in the FTZ group was 73.8% after treatment. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. ② The GEE results showed that the post-treatment HbA1c levels in the two groups were not significantly different from each other. Moreover, the HbA1c level remained stable over treatment time. ③ MLRA and subgroup analyses results demonstrated that FTZ was more effective in patients with high baseline HbA1c [<italic>β</italic>=-0.530,95% confidence interval(CI) -0.850~-0.209,<italic>P</italic><0.01] or those who were complicated with hypertension (<italic>β</italic>=-0.918,95%CI -1.614~-0.222,<italic>P</italic><0.05). Conclusion:In the real world, FTZ is able to control the blood sugar, and its effect is similar to those of conventional hypoglycemic drugs. Besides, it is capable of stabilizing the blood sugar for a long time.

7.
Article in Chinese | WPRIM | ID: wpr-905808

ABSTRACT

Objective:To determine the association between recreational drug usage, high risk sexual behavior, and HIV infection among men who have sex with men(MSM) in Jinhua. Methods:A cross-sectional survey was conducted to recruit MSM for anonymous questionnaire survey and serological examination. We used EpiData3.1 for data entry and SPSS 19.0 for statistical analysis. Results:A total of 368 MSM were surveyed, in which the proportion of recreational drug usage was 13.3% ( 49 / 368 ), with the HIV infection of 10.3% (38/ 368 ) and syphilis infection of 8.9% (25/368). Risk factors associated with recreational drug usage were determined to be part-time job or being unemployed (OR=5.26; 95%CI: 2.10-13.18; P<0.001), average monthly income ≥CNY 5 000 (OR=6.45; 95%CI: 2.87-14.61; P<0.001), education level of high school or above (OR=1.56; 95%CI: 1.37-3.57; P=0.037), sexual orientation being homosexual(OR=3.52; 95%CI: 1.60-7.33; P=0.002), number of sexual partners >1 (OR=4.37; 95%CI: 1.76-10.82; P=0.001), engaged in group sex (OR=7.90; 95%CI: 2.11-29.55; P=0.002) and previously diagnosed sexually transmitted diseases (OR=4.76; 95%CI: 1.29-17.65;P=0.019). Conclusion:Prevalence of recreational drug usage among MSM in Jinhua is relatively low. MSM with part-time or unemployed status, monthly income ≥CNY 5 000, higher education level, homosexual orientation, multiple sexual partners, sexually transmitted diseases and group sex behavior are the risk factors associated with recreational drug usage in Jinhua city. Targeted countermeasures should be considered for intervention.

8.
Acta Pharmaceutica Sinica ; (12): 1063-1069, 2021.
Article in Chinese | WPRIM | ID: wpr-886991

ABSTRACT

Abnormal aggregation of amyloid-β protein (Aβ) in brain plays a vital role in the occurrence of Alzheimer's disease (AD). Hence, inhibiting Aβ aggregation is one major tactic for therapy of AD. Previous studies have found that tolcapone can inhibit Aβ42 aggregation and reduce the cytotoxicity induced by Aβ42 aggregates, but clinical studies have found that tolcapone has strong liver toxicity. To reduce the liver toxicity of tolcapone, its side chain structure was modified to obtain its derivative phenethyl (E)-2-cyano-3-(3,4 dihydroxy-5-nitrobenzene)-acrylate (PCDNA). Thioflavin T (ThT) and atomic force microscopy (AFM) assays were used to explore the inhibitory effect of PCDNA on Aβ42 fibrillogenesis. The cytotoxicity assays were used to explore the inhibitory effect of PCDNA against the cytotoxicity induced by Aβ42 aggregates. In addition, the depolymerization effect of PCDNA on mature Aβ42 fibrils was also explored. Finally, molecular docking was used to explore the interaction between PCDNA and Aβ42 pentamer. These results lay the foundation for the study of the structural analogues of tolcapone as Aβ inhibitors.

9.
Chinese Journal of School Health ; (12): 983-986, 2021.
Article in Chinese | WPRIM | ID: wpr-886302

ABSTRACT

Objective@#To determine the relationship between peer attachment and quality of life among adolescents in Chongqing, to provide scientific basis for intervention of quality of life.@*Methods@#A total of 6 073 respondents were selected from 5 middle schools and 6 primary schools in a district of Chongqing in December 2017 by stratified cluster sampling method. The revised Chinese version of Adolescent Attachment Questionnaire (IPPA-R) Peer Attachment Subscale and Adolescent Children s Quality of Life Scale were used to conduct the survey.@*Results@#The total score of life quality of students with secure attachment type (144.97±17.39) was significantly higher than that of students with insecure attachment type(136.45±17.75)(t=18.90,P<0.01). The scores of four dimensions of life quality of students with secure attachment[(30.40±5.11)(39.42±6.42)(53.45±7.99)(21.73±3.69)] were significantly higher than those of students with insecure attachment[(29.54±5.15)(37.87±6.66)(49.02±8.69)(20.02±3.60)](P<0.05). Multivariate stepwise regression analysis showed that peer attachment was correlated with physical, psychological, social, adolescent dimensions and the total score of life quality(B=0.28,0.03,0.05,0.14,0.05,P<0.05).@*Conclusion@#Adolescent peer attachment is positively correlated with the total score and specific dimensions of life quality. Improving the safety of peer attachment is helpful to improve life quality among adolescents.

10.
Chinese Journal of School Health ; (12): 973-976, 2021.
Article in Chinese | WPRIM | ID: wpr-886300

ABSTRACT

Objective@#To explore the relationship between pubertal knowledge-attitude-practice(KAP) and quality of life (QoL) of left-behind children in adolescence, and to provide a scientific reference for making measures to improve QoL of left-behind children.@*Methods@#In December 2017, 3 524 left-behind children from 5 primary schools and 5 middle schools in Chongqing were selected by stratified cluster sampling method carry out the Quality of Life Scale of adolescent children and the Questionnaire of Adolescent Knowledge and Belief.@*Results@#The scores of total QoL, physicaland social dimensions of left-behind children[(140.81±17.19)(30.05±5.07)(50.99±8.32)points, respectively]were lower than those of non-left-behind children[(141.81±17.53)(30.35±5.06)(51.73±8.44)point, respectively](P<0.05). Gender, School period, puberty timing, family rearing pattern and economic status had significant influence on the QoL of left-behind children (P<0.05). The adolescent attitude and behavior had a positive effect on total QoL and the scores of physical, psychological, social and adolescent dimensions of left-behind children(B=0.62, 0.08, 0.11, 0.30, 0.13;0.77, 0.11, 0.20, 0.26, 0.19, P<0.01); and knowledge had a positive effect on the adolescence of QoL(B=0.04, P<0.01).@*Conclusion@#The adolescent attitude, behavior and quality of life of left-behind children were positively correlated. Strengthening adolescent health education for left-behind children, focusing on conveying correct adolescent attitude to students, and promoting the transformation of correct attitude to positive practice, can improve the QoL of adolescent left-behind children.

11.
Article in Chinese | WPRIM | ID: wpr-881487

ABSTRACT

Objective:To analyze the sexual relationship power and its influencing factors in married couples with single human immunodeficiency virus (HIV) positive spouse, and to provide theoretical support for the development of appropriate HIV prevention and control measures. Methods:Data of HIV single positive couples were collected from the database of AIDS epidemic. Social demographic characteristics, AIDS related knowledge, sexual behavior and sexual relationship power of HIV single positive couples were obtained by self-designed questionnaire. Current situation and influencing factors of sexual relationship power of the negative spouses HIV single positive couples' were analyzed. Results:Among 191 HIV negative spouses, 72.3% had not heard of AIDS, 3.1% had a history of HIV testing, and 38.2% had high sexual power. Single factor analysis found that men (χ2 =12.227,P<0.001), high income (χ2 =4.227,P =0.040), high education level (χ2 =18.188,P<0.001), frequent drinking (χ2= 6.104,P=0.013), and high-level awareness of AIDS (χ2=10.827,P=0.013) had higher power of sexual relationship. Multivariate analysis showed that men and individuals with college education or above had higher sexual power, with OR (95% CI) 4.102 (1.757-9.578) and 7.403 (2.810-19.503), respectively. Conclusion:The low awareness rate of AIDS knowledge and the disharmonious relationship between husband and wife will increase the risk of AIDS transmission in the spouses. Male, economic income, education level and AIDS awareness rate are the important influencing factors of sexual relationship power.

12.
Article in Chinese | WPRIM | ID: wpr-879874

ABSTRACT

OBJECTIVE@#To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD).@*METHODS@#From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc.@*RESULTS@#The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children (@*CONCLUSIONS@#The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.


Subject(s)
Autism Spectrum Disorder , Child , China , Copper/analysis , Humans , Trace Elements/analysis , Zinc
13.
Article in Chinese | WPRIM | ID: wpr-911714

ABSTRACT

Objective:To analyze the disease composition and characteristics among elderly patients with multimorbidity in Jing′an district of Shanghai.Methods:A total of 68 147 patients aged 60 and above in Shanghai Jing′an district were selected in the study by stratified random sampling method, The clinical data of patients from January 2017 to December 2018 were obtained from hospital information system, the status of multimorbidity, the disease composition and characteristics were analyzed with SPSS software.Results:Among 68 147 elderly patients, 43 953 had 2 or more chronic diseases. The top five chronic diseases were hypertension, chronic ischemic heart disease, diabetes, hyperlipidemia, and cerebrovascular disease. There was significant difference in prevalence of multimorbidity between male and female patients (χ 2=15.276, P<0.01); compared to males, females had higher prevalence of multimorbidity ( OR=1.152, P<0.01). There was significant difference in prevalence of multimorbidity among different age groups of patients (χ 2= 48.547, P<0.01); compared to age group 60-69, patients age 70-79 ( OR = 1.629, P<0.01) and aged 80 and above ( OR=2.686, P<0.01) had higher prevalence of multimorbidity. When 4 chronic diseases coexist, male urinary system diseases and female joint diseases rank in the top five comorbid diseases, while when 5 chronic diseases coexist, female sleep disorders rank in the top five positions. For patients aged ≥80 years, when 5 chronic diseases coexist, diabetes mellitus is no longer among in the top five comorbid diseases. Conclusions:The elderly women and older-aged patients have higher prevalence of multiomorbidity. Hypertension is still the top priority of chronic disease prevention and control for the elderly in the community. It is suggested to establish the precise prevention and control mechanism for the aging chronic disease.

14.
Acta Pharmaceutica Sinica ; (12): 1614-1621, 2020.
Article in Chinese | WPRIM | ID: wpr-823313

ABSTRACT

This research investigated the mechanism by which bupivacaine inhibits glutamate-induced intracellular free Ca2+ increases in primary cultured hippocampal astrocytes. Immunofluorescence was used to demonstrate the expression of metabotropic glutamate receptor (mGluR5 receptor) on neurons and astrocytes. Calcium imaging was used to measure the alteration of intracellular free Ca2+ ([Ca2+]i) in primary cultured rat hippocampal neurons and astrocytes. The animal experiments were approved by the Animal Experiments Ethical Committee of Hebei Medical University. The results showed that mGluR5 receptor was abundantly expressed in the primary cultured rat neurons and astrocytes. Bupivacaine (300 μmol·L-1) significantly inhibited 1 mmol·L-1 glutamate-induced [Ca2+]i increase in astrocytes (P < 0.01). 2-Methyl-6-(2-phenylethynyl)-pyridine (MPEP) (10 μmol·L-1) completely abolished the increase of [Ca2+]i induced by 1 mmol·L-1 glutamate in the astrocytes (P < 0.01), while the inhibitory effect on neurons was only 10%-20%. Bupivacaine (300 μmol·L-1) completely inhibited the [Ca2+]i increase induced by mGluR5 receptor agonists (RS)-3,5-dihydroxyphenylglycine (DHPG) (50 μmol·L-1) and (RS)-2-chloro-5-hydroxyphenylglycine sodium salt (CHPG) (1 mmol·L-1) in astrocytes (P < 0.01). In addition, bupivacaine inhibited the CHPG-induced [Ca2+]i increase in a dose-dependent manner in astrocytes with an IC50 of 100 μmol·L-1. The results from this study indicate that bupivacaine inhibits glutamate-induced [Ca2+]i elevation by acting on the mGluR5 receptor in primary cultured hippocampal astrocytes.

15.
Journal of Medical Postgraduates ; (12): 274-279, 2020.
Article in Chinese | WPRIM | ID: wpr-818418

ABSTRACT

ObjectiveThe local recurrence or distant metastasis of colorectal cancer (CRC) after surgical resection still directly affects the prognosis of CRC patients.This study aims to investigate the clinical significance of preoperative peripheral blood fibrinogen (Fbg) level combined with platelet-to-lymphocyte ratio (PLR) in the prognosis of CRC.MethodsThe clinicopathological characteristics of 108 CRC patients who were diagnosed by pathology and underwent surgical resection in Wujin hospital affiliated to Jiangsu University from January 2013 to December 2015 were analyzed. Fbg and PLR thresholds were determined by ROC curve, and the patients were grouped according to Fbg combined with PLR (F-PLR) to analyze the relationship between different F-PLR scores and the clinicopathological characteristics and prognosis of CRC patients.ResultsPLR showed statistically significant difference in the left and right half of the tumor (P0.05). Multivariate analysis using COX regression showed that F-PLR score, TNM stage and lymph node metastasis were independent risk factors for the prognosis of CRC patients (P<0.05).ConclusionThe F-PLR score (Fbg and PLR combined) can be used as a predictor of treatment effect and prognosis of CRC patients to guide clinical treatment decisions and prognoses.

16.
Acta Physiologica Sinica ; (6): 777-784, 2020.
Article in Chinese | WPRIM | ID: wpr-878225

ABSTRACT

The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.


Subject(s)
Animals , Dentate Gyrus , Dopamine , Hippocampus , Male , Maze Learning , Rats , Rats, Sprague-Dawley , Spatial Learning , Spatial Memory
17.
Article | WPRIM | ID: wpr-831097

ABSTRACT

Purpose@#Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. @*Materials and Methods@#In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. @*Results@#AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. @*Conclusion@#Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

18.
Article | WPRIM | ID: wpr-831079

ABSTRACT

Purpose@#Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. @*Materials and Methods@#We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings. @*Results@#In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. @*Conclusion@#Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

19.
Journal of Medical Postgraduates ; (12): 592-597, 2020.
Article in Chinese | WPRIM | ID: wpr-821834

ABSTRACT

ObjectiveRenal fibrosis is the basic pathological process of chronic kidney disease. To explore the protective effect of sildenafil (Sil) on renal fibrosis in mice, and provide experimental evidence for the clinical application of sildenafil in the treatment of renal fibrosis.Methods90 Kunming mice were randomly divided into three groups. Sham operation group (n=30), the mice only had ureteral separation, no ligation and ureteral clipping, which was subcutaneously injected with 0.9% NaCl solution in dose of 1 mL/(10 g·d); UUO model group (n=30), the UUO model was prepared by separating and ligating ureters in mice, and those were given subcutaneous injection with 0.9% NaCl solution in 1 mL/(10 g·d); UUO+Sil medicated group (n=30), mice were subcutaneously injected with sildena in 12 mg/(kg·d) at the same time every day for 14 days from the 1st day of UUO model. On the 3rd, 7th and 14th day, 10 mice whoes blood from eyeball was collected to determine serum creatinine and urea nitrogen were randomly selected from each group. HE and Masson staining were performed on the left kidney tissue to observe the pathological changes of the kidney tissue. The levels of Akt and GSK-3β protein and its phosphorylation in renal tissue were determined by western blot.ResultsAfter 3 days in UUO model, the contents of serum creatinine (63.10±2.90mol/L ) and urea nitrogen (12.87±0.40mmol/L) in the UUO group were significantly higher than those in the sham group [(26.00±3.70) mol/L, (8.07±0.60) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (13.59±0.30) mmol/L] on the 7th day were higher than those in the sham group [(29.18±3.50) mol/L, (9.14±0.50) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (15.03±0.50) mmol/L] on the 14th day were also significantly higher than those in the sham group [(29.74±2.50) mol/L, (9.90±0.20) mmol/L] (P<0.05). Compared with UUO group, the creatinine of mice on the 3rd, 7th and 14th day in the medicated group was lower (P<0.05). Compared with UUO group , urea nitrogen on the 3rd, 7th and 14th day in the medicated group was decreased (P<0.05). Compared with the sham operation group, the expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the UUO group were significantly decreased (P<0.05), while the protein expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the medicated group were significantly increased compared with the UUO group (P<0.05). On the 7th day in UUO model, there were many changes included atrophic renal tubular epithelial cells, dilated lumen, widened interstitium and more infiltrated inflammatory cells. On the 14th day in UUO, the above changes were more obvious, interstitial fibroblast hyperplasia and interstitial fibrosis, and the above pathological changes were reduced in the medicated group compared with the UUO model group. The collagen fibers in the UUO model group increased gradually with time. On the 14th day in UUO, the collagen fibers in the interstitium increased significantly, the tubular epithelium was damaged, and the red staining cells became lighter. These findings were less severe in the medicated group than in the UUO model group.ConclusionSildenafil can alleviate renal damage caused by renal fibrosis. Sildenafil inhibited renal fibrosis in UUO model, and its mechanism may be related to up-regulation of Akt/GSK3β pathway.

20.
Journal of Medical Postgraduates ; (12): 592-597, 2020.
Article in Chinese | WPRIM | ID: wpr-821814

ABSTRACT

ObjectiveRenal fibrosis is the basic pathological process of chronic kidney disease. To explore the protective effect of sildenafil (Sil) on renal fibrosis in mice, and provide experimental evidence for the clinical application of sildenafil in the treatment of renal fibrosis.Methods90 Kunming mice were randomly divided into three groups. Sham operation group (n=30), the mice only had ureteral separation, no ligation and ureteral clipping, which was subcutaneously injected with 0.9% NaCl solution in dose of 1 mL/(10 g·d); UUO model group (n=30), the UUO model was prepared by separating and ligating ureters in mice, and those were given subcutaneous injection with 0.9% NaCl solution in 1 mL/(10 g·d); UUO+Sil medicated group (n=30), mice were subcutaneously injected with sildena in 12 mg/(kg·d) at the same time every day for 14 days from the 1st day of UUO model. On the 3rd, 7th and 14th day, 10 mice whoes blood from eyeball was collected to determine serum creatinine and urea nitrogen were randomly selected from each group. HE and Masson staining were performed on the left kidney tissue to observe the pathological changes of the kidney tissue. The levels of Akt and GSK-3β protein and its phosphorylation in renal tissue were determined by western blot.ResultsAfter 3 days in UUO model, the contents of serum creatinine (63.10±2.90mol/L ) and urea nitrogen (12.87±0.40mmol/L) in the UUO group were significantly higher than those in the sham group [(26.00±3.70) mol/L, (8.07±0.60) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (13.59±0.30) mmol/L] on the 7th day were higher than those in the sham group [(29.18±3.50) mol/L, (9.14±0.50) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (15.03±0.50) mmol/L] on the 14th day were also significantly higher than those in the sham group [(29.74±2.50) mol/L, (9.90±0.20) mmol/L] (P<0.05). Compared with UUO group, the creatinine of mice on the 3rd, 7th and 14th day in the medicated group was lower (P<0.05). Compared with UUO group , urea nitrogen on the 3rd, 7th and 14th day in the medicated group was decreased (P<0.05). Compared with the sham operation group, the expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the UUO group were significantly decreased (P<0.05), while the protein expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the medicated group were significantly increased compared with the UUO group (P<0.05). On the 7th day in UUO model, there were many changes included atrophic renal tubular epithelial cells, dilated lumen, widened interstitium and more infiltrated inflammatory cells. On the 14th day in UUO, the above changes were more obvious, interstitial fibroblast hyperplasia and interstitial fibrosis, and the above pathological changes were reduced in the medicated group compared with the UUO model group. The collagen fibers in the UUO model group increased gradually with time. On the 14th day in UUO, the collagen fibers in the interstitium increased significantly, the tubular epithelium was damaged, and the red staining cells became lighter. These findings were less severe in the medicated group than in the UUO model group.ConclusionSildenafil can alleviate renal damage caused by renal fibrosis. Sildenafil inhibited renal fibrosis in UUO model, and its mechanism may be related to up-regulation of Akt/GSK3β pathway.

SELECTION OF CITATIONS
SEARCH DETAIL