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1.
Chinese Pharmacological Bulletin ; (12): 565-573, 2024.
Article in Chinese | WPRIM | ID: wpr-1013655

ABSTRACT

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

2.
Chinese Pharmacological Bulletin ; (12): 46-54, 2024.
Article in Chinese | WPRIM | ID: wpr-1013605

ABSTRACT

Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect. Methods Cellular oxidative stress models were used, different concentrations of curcumin were added to determinethebone formation markers, and the potential signaling pathways involvedwere detected. Meanwhile, the mouse model of osteoporosis ( ovariecto- mized, 0VX) was used to confirm its effect against osteoporosis. Results In vitro experiments found that low concentrations of curcumin (1-10 μmol · L

3.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 911-919, 2023.
Article in Chinese | WPRIM | ID: wpr-1015609

ABSTRACT

Oxidative stress is a state of redox imbalance, and it easily leads to oxidative damage in an organism. The main mechanism of oxidative stress is to regulate the redox balance by activating the antioxidant system. As an important signaling molecule, hydrogen sulfide(H

4.
Chinese Pharmacological Bulletin ; (12): 386-391, 2023.
Article in Chinese | WPRIM | ID: wpr-1013867

ABSTRACT

Aim To explore the effect of Buyang Huanwu Decoction on cerebral ischemia-reperfusion injury in rats by regulating autophagy through PI3K/AKT pathway. Methods The rats were randomly divided into five groups(n=10): sham operation group(Sham), model group(Model), Buyang Huanwu Decoction group(BYHWD), PI3K inhibitor group(LY294002)and Vehicle group(Vehicle). Except Sham group, the other groups were treated with 2h ischemia and 72 h reperfusion for modeling. The Zea Longa score was used to assess the neurological defects, HE was used to observe brain injury in the ischemic penumbra(IP), immunofluorescence was employed to detect LC3, and Western blot was used to detect pathway and autophagy marker proteins. Results Compared BYHWD group with model group, the neurological score of rats decreased, cerebral infarction volume decreased, the pathological lesions of brain IP were relieved, PI3K and p-AKT/AKT expression increased, and LC3Ⅱ/ decreased and p62 increased(P<0.05). The regulatory effect of BYHWD was weakened by LY294002(P<0.05). Conclusion Buyang Huanwu Decoction alleviates cerebral ischemia-reperfusion injury in rats by activating PI3K/AKT pathway to inhibit autophagy.

5.
Chinese Pharmacological Bulletin ; (12): 244-251, 2023.
Article in Chinese | WPRIM | ID: wpr-1013850

ABSTRACT

Aim To investigate the effect of luteolin on M1 macrophages polarization through HIF-1α-mediated glycolytic pathway. Methods RAW264.7 cells were divided into control groups(M0)and LPS+IFN-γ groups(M1). M1 groups were further divided into luteolin group, 2-DG(glycolysis inhibitor)group, luteolin+2-DG group,luteolin+DMOG(HIF-1α agonist)group. The protein expression levels of iNOS, Arg-1 and HIF-1α were detected by Western blot. Macrophage phenotype was detected by flow cytometry. In addition, the expression levels of IL-6 and IL-10 were measured by ELISA. The gene expression levels of GLUT1, HK2, PFK1, PK and HIF-1α were quantified by quantitative real-time PCR. Results Compared with M1 groups, luteolin and luteolin+2-DG treatment groups decreased the expression levels of GLUT1, HK2, PFK1, PK and HIF-1α related to glycolysis. In addition, luteolin and luteolin+2-DG treatment group significantly inhibited the expression of M1 macrophage markers such as iNOS, CD86 and IL-6, whereas up-regulated M2 macrophage markers Arg-1, CD206 and IL-10. Notably, the inhibitory effects of luteolin on M1 macrophages were restored by DMOG. Conclusion Luteolin regulates M1 macrophage polarization by inhibiting the glycolytic pathway induced by HIF-1α.

6.
Chinese Pharmacological Bulletin ; (12): 1036-1041, 2023.
Article in Chinese | WPRIM | ID: wpr-1013778

ABSTRACT

Aim To investigate the effect of overexpression of silent information regulator 1 (Sirtl) on cardiac function in mice with myocardial ischemia. Methods Myocardial specific Sirtl overexpression transgenic mice (Sirtl-Tg) and littermate control mice (C57BL/6J), half male and half female, were randomly divided into control sham operation group (Con), control model group (Con +ISO), Sirtl overexpression sham operation group (Sirtl-Tg) and Sirtl overexpression model group (Sirtl-Tg + ISO). Isoproterenol (ISO) was injected subcutaneously into the back of the neck at 100 mg • kg

7.
Chinese Pharmacological Bulletin ; (12): 1507-1514, 2023.
Article in Chinese | WPRIM | ID: wpr-1013743

ABSTRACT

Aim To confirm the antidepressant effect of the volatile oil part of the disassembled prescription drugs (Chai Hu, Dang Gui and Bo He, referred to as CDB) from Xiaoyao Powder and investigate its mechanism via Nrf2/H0-1 signaling pathway on OB model rats. Methods GC-MS analysis of the main components of volatile oil part of CDB was performed. The rats were randomly divided into sham operation group, model group, fluoxetine hydrochloride group (FLX, 10 mg • kg

8.
Chinese Journal of Obstetrics and Gynecology ; (12): 833-837, 2023.
Article in Chinese | WPRIM | ID: wpr-1012292

ABSTRACT

Objective: To investigate the relationship between subchorionic hematoma (SCH) and coagulation status, autoantibodies, and conception method. Methods: A total of 100 pregnant women diagnosed with SCH from June 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University were included in the SCH group, while 100 healthy pregnant women during the same period were selected as the control group. The coagulation status (including platelet, prothrombin time, thrombin time, activated partial thromboplastin time, fibrinogen, antithrombin Ⅲ, fibrin degradation products, D-dimer, homocysteine, protein S activity, protein C activity), the positive rate of autoantibodies [including antiphospholipid antibodies (anticardiolipin antibody and anti-β2 glycoprotein Ⅰ antibody), antinuclear antibody] and the mode of conception of the two groups were analyzed. Results: Compared to the control group, the SCH group had higher levels of platelet [(240±45)×109/L vs (227±37)×109/L], fibrinogen [(4.0±0.8) vs (3.6±0.7) g/L], D-dimer [(0.42±0.18) vs (0.31±0.15) mg/L], blood homocysteine [(8.9±4.2) vs (6.9±2.3) μmol/L], and lower level of protein S activity [(55±14)% vs (68±20)%], and there were significant differences between the two groups (all P<0.05). The SCH group had higher positive rates of autoantibodies [24.0% (24/100) vs 8.0% (8/100)], antiphospholipid antibodies [15.0% (15/100) vs 6.0% (6/100)], anti-β2 glycoprotein Ⅰ antibody [10.0% (10/100) vs 3.0% (3/100)], antinuclear antibody [11.0% (11/100) vs 2.0% (2/100)] and assisted reproduction rate [10.0% (10/100) vs 2.0% (2/100)] than those of the control group (all P<0.05). Conclusion: The occurrence of SCH is related to blood hypercoagulability, positive autoantibodies, and assisted reproduction.


Subject(s)
Pregnancy , Female , Humans , Autoantibodies , Antibodies, Antinuclear , Antibodies, Antiphospholipid , Fibrinogen , Homocysteine , Glycoproteins
9.
Acta Pharmaceutica Sinica ; (12): 2461-2467, 2023.
Article in Chinese | WPRIM | ID: wpr-999102

ABSTRACT

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

10.
Acta Pharmaceutica Sinica ; (12): 3366-3378, 2023.
Article in Chinese | WPRIM | ID: wpr-999088

ABSTRACT

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

11.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 382-384, 2023.
Article in Chinese | WPRIM | ID: wpr-993608

ABSTRACT

The main goal of radioactive iodine (RAI) administrated for patients with indeterminate-risk differentiated thyroid cancer (DTC) is removing occult microscopic residual disease after a total thyroidectomy, aiming to reduce recurrence and metastasis, then to improve disease-free survival. This treatment is called as adjuvant therapy, which also ablates the remnant thyroid tissue together. According to the current thyroid cancer management guidelines (2015 American Thyroid Association management guidelines), intermediate-risk patients can be selectively administered RAI. By reviewing articles about DTC patients with indeterminate-risk who underwent RAI or not after thyroidectomy, this article shows that there are inconsistent opinions on 131I decreasing recurrence and improving survival. In addition, apart from unexplained hyperthyroglobulinemia as an indication for 131I therapy, no other uniform clinicalpathological characteristics are recommended.

12.
Chinese Journal of Medical Education Research ; (12): 1187-1191, 2023.
Article in Chinese | WPRIM | ID: wpr-991498

ABSTRACT

Clinical post competence and medical ethics literacy are the key qualities that applied medical talents should have. The synergy of medical education is an effective way to deepen the reform of competence-oriented medical education. Under the background of synergy of medical education and considering the orientation of training applied medical talents in our college, we explore a progressive path of "three early education", which means early exposure to specialties, early exposure to practice, and early exposure to clinical practice. Meanwhile, we strengthen the cultivation of medical students' medical ethics literacy throughout the whole process of "three early education", laying a solid foundation for medical students before they enter the stage of clinical practice training. Practice shows that the progressive "three early education" mode and the cultivation of medical ethics literacy throughout the whole process can effectively improve medical students' clinical post competence.

13.
China Tropical Medicine ; (12): 742-2023.
Article in Chinese | WPRIM | ID: wpr-979832

ABSTRACT

@#Abstract: Objective To analyze the effect of adjuvant to levofloxacin in the treatment of retreatment smear positive pulmonary tuberculosis, as well as its effect on respiratory function, immune function and inflammatory factors. Methods One hundred cases of retreatment smear positive pulmonary tuberculosis patients admitted to Rudong County People's Hospital in Nantong city in Jiangsu province from 2017 to 2021 were randomly divided into a control group (n=50) and an observation group (n=50) according to random number table method. Both groups received conventional treatment (3 months of isoniazid, rifampicin, ethambutol, pyrazinamide / 6 months of isoniazid, rifampicin, ethambutol), with levofloxacin added to the control group, and thymopentin added to the observation group for the first three months in addition to routine treatment. The treatment effect of the two groups were compared. Results The sputum smear conversion rate of the observation group was significantly higher than that of the control group after 3 months and 5 months of treatment (χ2=7.142, P<0.05; χ2=6.250, P<0.05). The cavity absorption time and lesion absorption time in the observation group were significantly lower than those in the control group (t=4.006, P<0.05; t=5.165, P<0.05). The turning time of bacteriological culture in the observation group was significantly lower than that in the control group (t=4.220,P<0.05). After 3 months of treatment, CD4+, CD3+, CD4+/CD8+ of the observation group were higher than those of the control group, the differences were statistically significant (t=8.885, P<0.05; t=6.274, P<0.05; t=4.357, P<0.05). After 3 months of treatment, the IFN-γ (interferon-γ) of the observation group was higher than that of the control group (t=8.892, P<0.05), whereas the , IL-10 (interleukin-10) was significantly lower than that in the control group (t=5.986, P<0.05). After 3 months of treatment, forced vital capacity (FVC), forced expiratory volume in one second (forced expiratory volume in one second, FEV 1) and the one-second rate (forced expiratory volume in one second / forced vital capacity, FEV1/FVC) in the observation group were significantly higher than those in the control group (t=11.223, P<0.05; t=10.128, P<0.05; t=4.464, P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2=0.378, P>0.05). Conclusions Thymopentin combined with levofloxacin had a significant application effect in the treatment of retreatment smear positive pulmonary tuberculosis, s, which led to improved inflammatory reaction, respiratory function and immune function. Additionally, it can increase sputum smear conversion rate and accelerate patient recovery, improving overall treatment efficacy, with a relatively high clinical application value.

14.
Neuroscience Bulletin ; (6): 962-972, 2023.
Article in English | WPRIM | ID: wpr-982443

ABSTRACT

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.


Subject(s)
Acoustic Stimulation/methods , Neurons/physiology , Auditory Cortex/physiology , Auditory Perception , Pyramidal Cells
15.
Journal of Experimental Hematology ; (6): 889-895, 2023.
Article in Chinese | WPRIM | ID: wpr-982146

ABSTRACT

OBJECTIVE@#To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).@*METHODS@#From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve.@*RESULTS@#Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001).@*CONCLUSION@#Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.


Subject(s)
Humans , Lymphohistiocytosis, Hemophagocytic , Clinical Relevance , ROC Curve , Sensitivity and Specificity , Lupus Erythematosus, Systemic
16.
Journal of Forensic Medicine ; (6): 115-120, 2023.
Article in English | WPRIM | ID: wpr-981844

ABSTRACT

OBJECTIVES@#To estimate postmortem interval (PMI) by analyzing the protein changes in skeletal muscle tissues with the protein chip technology combined with multivariate analysis methods.@*METHODS@#Rats were sacrificed for cervical dislocation and placed at 16 ℃. Water-soluble proteins in skeletal muscles were extracted at 10 time points (0 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d, 8 d and 9 d) after death. Protein expression profile data with relative molecular mass of 14 000-230 000 were obtained. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) were used for data analysis. Fisher discriminant model and back propagation (BP) neural network model were constructed to classify and preliminarily estimate the PMI. In addition, the protein expression profiles data of human skeletal muscles at different time points after death were collected, and the relationship between them and PMI was analyzed by heat map and cluster analysis.@*RESULTS@#The protein peak of rat skeletal muscle changed with PMI. The result of PCA combined with OPLS discriminant analysis showed statistical significance in groups with different time points (P<0.05) except 6 d, 7 d and 8 d after death. By Fisher discriminant analysis, the accuracy of internal cross-validation was 71.4% and the accuracy of external validation was 66.7%. The BP neural network model classification and preliminary estimation results showed the accuracy of internal cross-validation was 98.2%, and the accuracy of external validation was 95.8%. There was a significant difference in protein expression between 4 d and 25 h after death by the cluster analysis of the human skeletal muscle samples.@*CONCLUSIONS@#The protein chip technology can quickly, accurately and repeatedly obtain water-soluble protein expression profiles in rats' and human skeletal muscles with the relative molecular mass of 14 000-230 000 at different time points postmortem. The establishment of multiple PMI estimation models based on multivariate analysis can provide a new idea and method for PMI estimation.


Subject(s)
Animals , Humans , Rats , Multivariate Analysis , Postmortem Changes , Protein Array Analysis , Technology
17.
Chinese Acupuncture & Moxibustion ; (12): 793-799, 2023.
Article in Chinese | WPRIM | ID: wpr-980797

ABSTRACT

OBJECTIVE@#To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD.@*METHODS@#A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3β (GSK-3β) in the hippocampus was detected.@*RESULTS@#There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3βwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3β was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05).@*CONCLUSION@#Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3β and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.


Subject(s)
Male , Animals , Rats , Rats, Sprague-Dawley , Glycogen Synthase Kinase 3 beta , Tubulin , Alzheimer Disease/therapy , tau Proteins/genetics , Acupuncture Therapy , Hippocampus
18.
Chinese Journal of Preventive Medicine ; (12): 868-876, 2023.
Article in Chinese | WPRIM | ID: wpr-985489

ABSTRACT

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.


Subject(s)
Humans , Hepatitis B virus/genetics , Hepatitis B, Chronic , Antiviral Agents/therapeutic use , DNA, Viral/therapeutic use , Retrospective Studies , Mutation , Drug Resistance, Viral/genetics , Lamivudine/therapeutic use
19.
Chinese Journal of Oncology ; (12): 375-381, 2023.
Article in Chinese | WPRIM | ID: wpr-984732

ABSTRACT

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.


Subject(s)
Female , Humans , Uterine Cervical Neoplasms/pathology , HeLa Cells , Fibronectins/metabolism , Culture Media, Conditioned , Carcinoma, Squamous Cell/metabolism , Adenocarcinoma , Cadherins/metabolism , RNA, Messenger/metabolism , Cell Movement , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Cell Proliferation , S100 Calcium Binding Protein A7/metabolism
20.
Chinese Journal of Cardiology ; (12): 626-632, 2023.
Article in Chinese | WPRIM | ID: wpr-984695

ABSTRACT

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.


Subject(s)
Humans , Male , Middle Aged , Aged , Coronary Artery Disease/diagnostic imaging , Stroke Volume , Myocardial Perfusion Imaging , Retrospective Studies , Ventricular Function, Left , Myocardial Ischemia
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