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1.
Article in Chinese | WPRIM | ID: wpr-934332

ABSTRACT

Objective:To investigate the detecting method and clinical characteristics of anti-nodal/paranodal antibodies in chronic inflammatory demyelinating polyradiculopathy.Methods:Serum samples were collected from 212 patients with chronic inflammatory demyelinating polyradiculopathy who were admitted to Huashan Hospital of Fudan University or from other clinical centers from January 2018 to July 2021. Autoantibodies (anti-NF155, anti-NF186, anti-CNTN1) and IgG subtypes were detected with cell-based assay. According to the test results, patients were divided into anti-NF155 positive group, anti-NF186 positive group and anti-CNTN1 positive group, clinical characteristics of patients in each group, including limb weakness, superficial sensation and proprioception, tremor, cerebrospinal fluid protein level, brachial plexus magnetic resonance (MRI) were retrospectively analyzed and compared.Results:A total of 23 patients (10.8%,23/212) were positive for anti-NF155 antibody, 12 (5.7%,12/212) for anti-NF186 antibody, and 4 (1.9%,4/212) for anti-CNTN1 antibody. IgG 4 was the predominant subtype in anti-NF155 and anti-CNTN1 groups. In the anti-NF186 group, all cases were IgG positive and antibody subtypes could be detected in 4 cases (4/12). In anti-NF155 group, 23 patients (100%,23/23) had limb weakness and deep sensory disturbance, 19 patients (82.6%,19/23) had superficial sensory disturbance, 22 patients (95.7%,22/23) were symmetrically involved, 18 patients (78.3%,18/23) showed tremor, 19 patients (19/19) showed abnormal in brachial plexus MRI. In anti-NF186 group, 12 patients had limb weakness (12/12), 9 patients (9/12) and 6 patients (6/12) had superficial sensory disturbance and deep sensory disturbance respectively, 8 patients (8/12) were asymmetrically involved, and only 1 patient (1/12) showed tremor, 1 (1/7) showed abnormal brachial plexus MRI. In anti-CNTN1 group, 4 cases showed symmetrical limb weakness and sensory disturbance, 3 patients had tremor, and four patients showed brachial plexus MRI abnormality. There were statistically significant differences in onset age, proprioception, tremor and MRI abnormalities of brachial plexus among the 3 groups ( P<0.01). Conclusions:The clinical characteristics of CIDP patients with anti-NF155, anti-NF186 and anti-CNTN1 antibodies are different. Screening anti-nodal/paranodal antibodies is of great significance for accurate diagnosis and treatment of patients with peripheral neuropathy.

2.
Article in Chinese | WPRIM | ID: wpr-933457

ABSTRACT

Objective:To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences.Methods:Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well.Results:A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions:There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

3.
Article in Chinese | WPRIM | ID: wpr-930133

ABSTRACT

Traditional Chinese Medicine (TCM) products could be registered as natural health products (NHPs) in Canada. Its registration process could be mainly divided into simple-application, traditional-application and non-traditional application. By analyzingi the TCM registration evidence system and its safety, effectiveness and quality required by different registration categories in Canada, we found that "simple-application" procesure needs to submit evidence based on the parameters of a component in the monograph. As for "traditional application", TCM products need to be used at least 50 years with, traditional material or Pharmacopoeia can be used as evidence; As for non-traditional application, TCM products need to provide evidence according to the disease risk level, and most of them need to provide scientific experiment evidence. Therefore, from the experience of TCM registration evidence system in Canada, the registration of TCM products should pay attention to improve the its classification method, refining its evidence requirements and data types, promoting the formulation of monograph of TCM, realizing the scientific evaluation and rapid review of classic famous prescriptions, and promoting the inheritance and innovative development of TCM in China.

4.
Article in Chinese | WPRIM | ID: wpr-930109

ABSTRACT

This paper analyzes the laws, regulations and concre measures of Traditional Chinese Medicine (TCM) in Canada, so as to provide reference for TCM products to enter Canada, and for the establishment of TCM regulation system and the improvement of its detailed rules in China. The regulation of TCM in Canadian, on the one hand, supervision is to provide guidance for the protection of consumers' rights and interests, including the guidance of rational drug use and rational purchase for consumers; on the other hand, it is to supervise enterprises, including the safety, effectiveness and quality certification of TCM products, labeling and packaging requirements, as well as the site certification of product manufacturing, packaging, labeling and import. The Ministry of health of Canada takes evidence as the core of evaluation, and ensures the safe and effective use of TCM products in Canada through product and site licensing evaluation. In the supervision of TCM, relevant departments in China should further strengthen the protection of consumers' drug rights and interests, strengthen the construction of TCM registration evidence system, and pay attention to the risk management of drug production quality.

5.
Article in Chinese | WPRIM | ID: wpr-930108

ABSTRACT

By searching for the Canadian Licensed Natural Health Products Database, (LNHPD), this paper analyzed the characteristics and current status of 92 Chinese patent medicines successfully registered and listed in Canada, and found that the enterprises of successfully registered enterprises are mainly located in areas with better development condition of Traditional Chinese Medicine (TCM) such as Beijing, Guangdong and Tianjin; The successfully registered Chinese patent medicines include 64 kinds of single medicine or medicine with single active ingredient (69.6%) and 28 kinds of compound medicine (30.4%), the forms of the dosage are mainly tablets and capsules, which have the characteristics of accuracy in dosage and stable physicochemical properties. There are also granules, solutions, powders and other dosage forms, which can be preserved for a long time and have low requirements on technic and environment. These Chinese patent medicines are mainly used to treat respiratory and circulatory system diseases, some are used to treat urogenital and digestive system diseases, and few are used to treat difficuilt diseases like tumors, diabetes. There are some other health care products. It is suggested to strengthen the connection between domestic standards of TCM registration and international standards, and promote the scientific and technological capacity of relevant enterprises, and encourage enterprises to strengthen international registration of advantageous products, so as to accelerate the speed of international development of TCM in China.

6.
Article in Chinese | WPRIM | ID: wpr-930093

ABSTRACT

Europe occupies an important position in the world herbal medicine market. The registration of Traditional Chinese Medicine (TCM) in EU is of great significance to the internationalization of TCM. The European Medicines Agency (EMA) has designed a relatively complete management system and regulatory guidelines for the registration and supervision of herbal medicinal products. The promulgation of the DIRECTIVE 2004/24/EC (2004 / 24 / EC) indicates that TCM could enter the EU market through simplified registration. Based on the registration conditions, registration authority and document guideines of Traditional Herbal Medicinal Products (THMPs) in EU, this paper analyzes the application requirements of simple registration of traditional herbal products in EU, and provides suggestions for the simplified registration of TCM in EU according to the registration requirements of medicinal history, quality requirements and application data format.

7.
Article in English | WPRIM | ID: wpr-927667

ABSTRACT

Objective@#This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB).@*Methods@#HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks.@*Results@#A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log 10 IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05).@*Conclusion@#There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.


Subject(s)
Biomarkers , Cytokines , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B, Chronic/drug therapy , Humans , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use
8.
Protein & Cell ; (12): 261-278, 2021.
Article in English | WPRIM | ID: wpr-880901

ABSTRACT

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

9.
Chinese Journal of Neurology ; (12): 1059-1063, 2021.
Article in Chinese | WPRIM | ID: wpr-911835

ABSTRACT

Overlap myoclonic epilepsy with ragged-red fibers (MERRF)-Leigh syndrome is a rare mitochondrial encephalomyopathy. A case of MERRF-Leigh syndrome associated with mitochondrial DNA 8344A>G (m.8344A>G) mutation was reported in this article. The patient has suffered from the disease since 15-year old with myoclonus, exercise intolerance, ataxia, limb weakness, dysphasia, dyspnea, blurred vision and hearing loss. Magnetic resonance imaging revealed lesions on right thalamus, bilateral medulla and lumbar spinal cord and atrophy of cervical spinal cord. Electromyography showed predominantly axonal damage of both sensory nerve and motor nerve. Histochemical analyses revealed ragged red fibers, ragged blue fibers, succinate dehydrogenase-stronghly reactive vessels and decreased cytochrome oxidase activity. Gene tests demonstrated a high level of m.8344A>G mutation and m. 14484T>C mutation. MERRF-Leigh overlap syndrome with m.8344A>G mutation was rare. Bulbar paralysis following myoclonus is the main clinical symptom.

10.
Acta Pharmaceutica Sinica ; (12): 3252-3260, 2021.
Article in Chinese | WPRIM | ID: wpr-906843

ABSTRACT

Drug combination can effectively enhance the anti-tumor effect, reduce the drug dose, and improve medication safety. The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo. Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f. Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect, but they are limited by poor water solubility and low tumor tissue delivery rate. In this study, a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology, particle size, potential, drug release, serum stability, and other properties. The immunogenicity, uptake behavior, and anti-cell proliferation ability of the biomimetic liposome was compared. All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (Chengdu, China). The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol (C+T/RBCm@Lip) in this study had an average particle size of 119.12 ± 2.78 nm and a spherical "core-shell" structure. The zeta potential value was -16.9 ± 1.2 mV, and the drug release behavior in vitro was slow. In addition, the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein, had good stability in serum, and could effectively avoid the recognition and clearance of macrophages, without causing immunogenicity in vivo. The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes, and the inhibitory effect on proliferation of HepG2 cells was enhanced. In conclusion, the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol, and could enhance the inhibitory effect on the growth of HepG2 liver cancer cells, providing a new idea for the anti-tumor application of Tripterygium wilfordii Hook f.

11.
Article in Chinese | WPRIM | ID: wpr-906145

ABSTRACT

Objective:To investigate the protective effect and molecular mechanism of Angelicae Sinensis Radix-Chuanxiong Rhizoma medicated serum (ASRCRS) against oxidative damage of PC12 cells induced by H<sub>2</sub>O<sub>2</sub>. Method:Oxidative damage of PC12 cells was induced by H<sub>2</sub>O<sub>2</sub><italic> in vitro</italic>, and intervention was performed in the low-, medium-, and high-dose ASRCRS groups with a final volume fraction of 15%. The cell viability was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell morphology was observed by an inverted fluorescence microscope. The content of lactate dehydrogenase (LDH) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the distribution of reactive oxygen species (ROS) in the cell supernatant were detected by the kits. Cell apoptosis was detected by Annexin V-FITC/PI double staining. The protein expression levels of nuclear factor E<sub>2</sub>-related factor 2 (Nrf2), Kelch-like epichlorohydrin associated protein-1 (Keap1), heme oxygenase-1 (HO-1), and SOD1 were detected by Western blot. Result:Oxidative damage was induced by 300 μmol·L<sup>-1</sup> H<sub>2</sub>O<sub>2</sub> for 24 hours. Compared with the normal group, the model group showed abnormal cell morphology, reduced cell viability (<italic>P</italic><0.01), increased LDH and MDA (<italic>P</italic><0.01), blunted SOD activity, elevated intracellular distribution of ROS, down-regulated protein expression of Nrf2, HO-1, and SOD1 (<italic>P</italic><0.05, <italic>P</italic><0.05), and up-regulated protein expression of Keap1 (<italic>P</italic><0.01). Compared with the model group, ASRCRS groups displayed improved cell morphology, increased cell viability, inhibited cell apoptosis, potentiated SOD activity (<italic>P</italic><0.01), suppressed release of LDH (<italic>P</italic><0.01) and generation of ROS, decreased content of MDA (<italic>P</italic><0.01), up-regulated protein expression of Nrf2, HO-1 and SOD1 (<italic>P</italic><0.05, <italic>P</italic><0.01), and down-regulated protein expression of Keap1 (<italic>P</italic><0.01). Conclusion:ASRCRS could protect PC12 cells from oxidative damage induced by H<sub>2</sub>O<sub>2</sub> by up-regulating the expression of Nrf2 to activate the Nrf2/antioxidant response element (ARE) signaling pathway, enhancing the ability to resist oxidative damage, and inhibiting cell apoptosis.

12.
Article in Chinese | WPRIM | ID: wpr-906138

ABSTRACT

Objective:Considering the efficacy of Gegen Qinliantang (GQT) in releasing exterior and clearing interior to alleviate dampness-heat dysentery, we analyzed the mechanism of the chloroform extract of GQT in alleviating enterotoxicity caused by irinotecan to provide an experimental basis for the development of GQT. Method:Kunming mice (<italic>n</italic>=60) were randomly divided into a blank group, a model group, a loperamide group (positive drug of loperamide hydrochloride capsule, 0.4 mg·kg<sup>-1</sup>), and high- (2.3 g·kg<sup>-1</sup>) and low-dose (1.16 g·kg<sup>-1</sup>) GQT chloroform extract groups. The mouse model of delayed diarrhea was established by intraperitoneal injection of irinotecan hydrochloride (CPT-11, 55 mg·kg<sup>-1</sup>) for four consecutive days, meanwhile, the mice in the blank group only received the same volume of normal saline. Corresponding drugs were administered by gavage on the fifth day, respectively, while the ones in the blank group and model group were given distilled water for five consecutive days. The general condition of mice in each group was observed, and diarrhea indexes of mice were recorded. Pathological changes in colon tissues of mice were observed by hematoxylin-eosin (HE) staining. The tumor necrosis factor (TNF)-<italic>α</italic>, interleukin (IL)-1<italic>β</italic>, cyclooxygenase (COX)-2, intercellular adhesion molecule (ICAM)-1, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) levels in colon tissues were detected with the assay kits. Furthermore, the expression levels of Kelch sample epoxy chloropropane associated protein 1 (Keap1), nuclear factor E<sub>2</sub> related factor 2 (Nrf2), tight junction protein-1 (ZO-1), heme oxygenase-1 (HO-1) and tight junction protein (Occludin) were detected by Western blot. Result:Compared with the blank group, the model group showed declined body weight and reduced contents of GSH-Px and SOD (<italic>P</italic><0.01), whereas increased diarrhea indexes and TNF-<italic>α</italic>, IL-1<italic>β</italic>, COX-2, ICAM-1, MDA and NO levels (<italic>P</italic><0.01). Abundant inflammatory cells and colonic mucosa with defects, swelling, bleeding, and inflammatory exudation were revealed by HE staining in the mice of the model group. The expression levels of Keap1, Nrf2, ZO-1, HO-1 and Occludin in colon tissues significantly declined (<italic>P</italic><0.01). Compared with the model group, the loperamide group and the high- and low-dose GQT chloroform extract groups exhibited improved weight loss, reduced diarrhea indexes, diminished TNF-<italic>α</italic>,<italic> </italic>IL-1<italic>β</italic>, COX-2, ICAM-1, MDA and NO, and elevated GSH-Px and SOD. HE staining indicated that the cells were compactly arranged with clear nuclei in the high- and low-dose GQT chloroform extract groups, and the expression levels of Keap1, Nrf2, HO-1, Occludin, and ZO-1 were up-regulated. Conclusion:GQT chloroform extract may alleviate CPT-11-induced delayed diarrhea by regulating inflammation and oxidative stress for enhancing the intestinal barrier function. These findings are expected to provide a reference for exploring the toxicity-attenuating effect of Chinese medicinals on chemotherapy drugs and for developing famous classical formulas.

13.
Article in Chinese | WPRIM | ID: wpr-905066

ABSTRACT

Objective:To investigate the effect of Huangjingwan (HW) on the activities of glycogen synthase kinase-3β (GSK-3β), protein phosphatase 2A (PP2A) and the mechanism in inhibiting tau protein hyperphosphorylation in the hippocampal neurons of mice with Alzheimer's disease. Method:After subcutaneous injection with 1.0% D-galactose (0.14 g·kg-1·d-1) into the back and neck of mice for 4 weeks, the right ventricle of mice was injected with 2 μL (75 ng) of okadaic acid for one time to make AD model, and the successfully modeled AD mice were selected by Morris water maze. Then, the selected AD mice were randomly divided into AD model group, memantine group (1.3×10-3 g·kg-1·d-1) and HW group (2.5 g·kg-1·d-1). In addition, the sham model control group and the normal control group were set up. At the same time, 2 μL normal saline was injected into the right ventricle of mouse in the sham model control group for modeling control. Two weeks after modeling, the mice in the two experimental drug groups were given the corresponding dose of the experimental drug by gavage for 4 weeks. In addition, after 2 weeks of AD modeling, mice in control group and AD model group were intragastrically administrated with the same amount of normal saline daily for 4 weeks. The mice in normal control group were only given daily feed. At the end of gavage, all the mice were tested by the open field experiment and jumping platform experiment to evaluate the differences in exploratory activity ability, anxiety level and learning and memory ability. The number of neurons in CA1 and CA3 areas of hippocampus in all the mice was detected by Nissl staining. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect mRNA expressions of GSK-3β and PP2A in hippocampus of mice in each group. Protein expressions of GSK-3β, PP2A, phosphorylated tau (p-tau) and total tau protein (t-tau) in hippocampus of mice in each group were detected by Western blot. Result:Compared with the normal control group, mice in AD model group showed an obvious dementia state, which was characterized by a lower spontaneous activity, lower exploration behavior ability, higher anxiety level, less movement and easier to stay and hide, longer learning response time, significantly increased number of learning and memory errors, and decreased numbers of hippocampal neuron in CA1 and CA3 areas, and reduced mRNA and protein expressions of PP2A, mRNA and protein expressions of GSK-3β, p-tau protein and the ratio of p-tau/t-tau were all increased significantly (P<0.01), while expression of t-tau protein was decreased, with no significant difference. Compared with the AD model group, mice in the HW group showed a higher spontaneous activity, higher exploration ability, lower anxiety level, higher learning and memory performance, and the numbers of hippocampal neuron in CA1 and CA3 areas increased, while mRNA and protein expressions of PP2A increased, and the mRNA and protein expressions of GSK-3β, the expression of p-tau protein and the ratio of p-tau/t-tau were all decreased significantly (P<0.01), but with no significant difference in the protein expression of t-tau. Conclusion:HW can inhibit tau hyperphosphorylation in hippocampal neurons of AD mice, restore tau protein function, protect hippocampal neurons, and exert an anti-AD effect, which may be related to the regulatory mechanism in the activity balance between GSK-3β and PP2A in hippocampal neurons.

14.
Article in Chinese | WPRIM | ID: wpr-905065

ABSTRACT

Objective:To explore the effect of Huangjingwan (HW) on the expressions of Wnt/β-catenin signal pathway-associated proteins in the hippocampus of mice with Alzheimer's disease (AD) induced by D-galactose and okadaic acid with learning and memory disorders, as well as its mechanism. Method:After subcutaneous injection with 1.0% D-galactose (0.14 g·kg-1·d-1) into the back and neck of mice for 4 weeks, the right ventricle of mice was injected with 2 μL(75 ng) of okadaic acid for one time to make AD model, and the successfully modeled AD mice were selected by Morris water maze. Then, the selected AD mice were randomly divided into AD model group, memantine group (1.3×10-3 g·kg-1·d-1) and HW group (2.5 g·kg-1·d-1). In addition, the sham model control group and the normal control group were set up. At the same time, 2 μL normal saline was injected into the right ventricle of mouse in the sham model control group as the modeling control. Two weeks after molding, the mice in the two experimental drug groups were given the corresponding dose of the experimental drug by gavage for 4 weeks. In addition, after 2 weeks of AD modeling, mice in sham model control group and AD model group were intragastrically administrated with the same amount of normal saline daily for 4 weeks. There was no special treatment in the normal control group. At the end of gavage, the shuttle experiment was performed to detect the differences in learning and memory levels of mice in each group. The changes of β-catenin and GSK-3β positive neurons in CA1 area of hippocampus in each group were tested by immunohistochemistry. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to measure the mRNA expressions of GSK-3β, β-catenin and CyclinD1 in hippocampus of mice in each group. The Western blot was used to detect the expressions of total GSK-3β (t-GSK-3β), phosphorylation of GSK-3β at Ser9 (p-Ser9-GSK-3β), phosphorylation of GSK-3β at Tyr216 (p-Tyr216-GSK-3β), total β-catenin (t-β-catenin), phosphorylation of β-catenin (p-β-catenin) and CyclinD1 proteins in hippocampus of mice in each group. Result:Compared with the normal control group, mice in AD model group showed an obvious dementia state, which was characterized by significant declines in learning and memory ability, the number of β-catenin immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-β-catenin and CyclinD1, the protein expressions of p-Ser9-GSK-3β, and the ratio of p-Ser9-GSK-3β/t-GSK-3β and p-Tyr216-GSK-3β/t-GSK-3β in hippocampal region (P<0.01), and significant increases in the number of GSK-3β immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-GSK-3β, the protein expressions of p-Tyr216-GSK-3β and p-β-catenin, the ratio of p-β-catenin/t-β-catenin in hippocampal region (P<0.01 respectively). Compared with the AD model group, the dementia symptoms of mice in HW group were significantly alleviated, and the number of β-catenin immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-β-catenin and CyclinD1, the protein level of p-Ser9-GSK-3β, the ratio of p-Ser9-GSK-3β/t-GSK-3β in hippocampal region were all significantly increased (P<0.01 respectively), whereas the number of GSK-3β immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-GSK-3β, the proteins expressions of p-Tyr216-GSK-3β and p-β-catenin, the ratio of p-β-catenin/t-β-catenin in hippocampal region were all significantly decreased (P<0.01 respectively), but the ratio of p-Tyr216-GSK-3β/t-GSK-3β has no significant statistical difference. Conclusion:HW shows the role of AD treatment, which can down-regulate the expression of GSK-3β in the hippocampus of AD mice and reduce its protein activity, and up-regulate the expression of β-catenin as well as increase its protein activity, so as to enhance the expression of downstream CyclinD1 and promote the transcription of the target genes. Its mechanism may be related to the activation of Wnt/β-catenin signal pathway.

15.
Article in Chinese | WPRIM | ID: wpr-905064

ABSTRACT

Objective:To treat mice with Alzheimer's disease (AD) with β-catenin RNA interference (RNAi) Huangjingwan (HW), so as to explore the neuroprotective signal mechanism of its prevention and treatment of AD. Method:A total of 81 male Kunming mice were randomly divided into normal control group, sham model control group, AD model group, Donepezil group, HW+scrambled group, HW+RNAi group, HW group, with 8 mice in each of donepezil group and HW group, and 13 mice in each of other groups. The AD models were established through injection with D-galactose and scopolamine in the last 5 groups for 5 consecutive weeks. On the 1st day of the 4th week after modeling, 0.75 μL PEI-LMW/β-catenin siRNAs nano-complex was injected into the right lateral ventricle of each mouse in for one time to treat with β-catenin RNAi in mice brains of the HW+RNAi group. The 0.75 μL complex was injected into the right lateral ventricle of each mouse for one time as for β-catenin interference control of the HW+scrambled group. The 0.75 μL normal saline was injected into the right lateral ventricle of each mouse in one time of the sham control group. Two weeks after intracerebroventricular injection, β-catenin RNAi was confirmed to be successful, and Donepezil (6.5×10-4 g·kg-1) was intragastrically administered to each mouse of donepezil group. HW (2.5 g·kg-1) was intragastrically administered to each mouse of HW group, HW+RNAi group and HW+scrambled group. Normal saline (0.5 mL·d-1) was intragastrically administered to each mouse of the sham control group. All gastric perfusion lasted for 4 weeks. At the end of gavage, the difference in learning and memory ability of mice was evaluated by platform jumping test. Nissl staining was used to count the number of neurons in s1Tr area of cerebral cortex and CA1 and CA3 areas of hippocampus of each mouse in each group. The mRNA expressions of Wnt1, DVL2, GSK-3β, β-catenin and CyclinD1 in mice brain of each group were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Western blot was used to detect the expressions of Wnt1, DVL2, GSK-3β, β-catenin and CyclinD1 in mice brain of each group. Result:The expression of β-catenin could be significantly inhibited through the injection with PEI-LMW/β-catenin siRNAs nano-complex into the lateral ventricle of AD mice, and nearly no β-catenin expression could be detected, which successfully achieved gene silencing. Compared with the normal control group, mice in AD model group showed that the learning and memory performance decreased significantly, the number of jumping errors increased (P<0.01), the number of neurons in S1Tr area of cerebral cortex and CA1, CA3 areas of hippocampus decreased significantly (P<0.01), the mRNA and protein expressions of Wnt1, DVL2, β-catenin, CyclinD1 in brain decreased significantly (P<0.01), while the mRNA and protein expressions of GSK-3β increased significantly (P<0.01). Compared with the AD model group, mice in HW group showed that the learning and memory performance increased significantly, the number of jumping errors decreased, the number of neurons in S1Tr area of cerebral cortex and CA1, CA3 areas of hippocampus increased significantly, the mRNA and protein expressions of Wnt1, DVL2, β-catenin, CyclinD1 in brain increased significantly, while the mRNA and protein expression of GSK-3β decreased significantly (P<0.01). Compared with the HW group, mice in HW+RNAi group showed that the learning and memory performance decreased significantly, the number of jumping errors increased significantly (P<0.01), the number of neurons in S1Tr area of cerebral cortex and CA1, CA3 areas of hippocampus decreased significantly (P<0.01), there was no significant change in mRNA and protein expressions of Wnt1, DVL2, GSK-3β in the brain, and the mRNA and protein expressions of β-catenin, CyclinD1 decreased significantly (P<0.01). Conclusion:HW can treat and prevent AD by activating Wnt/β-catenin signal pathway.

16.
Article in Chinese | WPRIM | ID: wpr-905063

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive memory and cognitive impairment and behavioral disorders, which has seriously threatened the health of the majority of middle-aged and elderly people. Traditional Chinese medicine (TCM) believes that the basic pathogenesis of AD is deficiency of kidney-essence, blood stasis and meridian stagnation. In recent years, many studies have shown that TCM has obvious value and advantages in the prevention and treatment of AD by multi-target mechanism. Therefore, it is of great significance to screen out effective anti-AD drugs from TCM compound prescriptions. Huangjingwan, also known as Jiuzhuan Huangjingwan, has the effects in tonifying kidney-essence, activating blood and removing stasis, with a potential effect in preventing AD. In this article, the feasibility of Huangjingwan in the prevention and treatment of AD was analyzed and discussed from the perspective of TCM theory, the study results of Huangjingwan in the prevention and treatment of AD were summarized, and the mechanism of its action was analyzed from the perspective of pharmacological mechanism. Based on TCM theory, Huangjingwan has the effect of anti-AD. According to relevant findings, Huangjingwan has many targets, such as anti-oxidation, anti-inflammatory, decrease of the level of oxidative stress in brain, activation of Wnt/β-catenin signal transduction in brain, regulation of glycogen synthase kinase-3β (GSK-3β), protein phosphatase 2A (PP2A) activity balance, reduction of amyloid β (Aβ) content and tau protein hyperphosphorylation in brain, so as to exert effects in improving neurological symptoms and increasing learning and memory ability, with an anti-AD neuroprotective function. This will provide new ideas for in-depth studies and clinical applications of Huangjingwan against AD.

17.
Article in English | WPRIM | ID: wpr-902453

ABSTRACT

Objective@#To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis. @*Materials and Methods@#Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signedrank test were performed to compare the objective measurements and the subjective image quality scores, respectively. @*Results@#With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, p 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT. @*Conclusion@#The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.

18.
Article in English | WPRIM | ID: wpr-894749

ABSTRACT

Objective@#To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis. @*Materials and Methods@#Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signedrank test were performed to compare the objective measurements and the subjective image quality scores, respectively. @*Results@#With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, p 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT. @*Conclusion@#The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.

19.
Chinese Journal of Cardiology ; (12): 572-579, 2021.
Article in Chinese | WPRIM | ID: wpr-941320

ABSTRACT

Objective: This study intends to explore the difference in the efficacy of PCSK9 inhibitors in patients with different FH phenotypes by analyzing the level of blood lipids before and after treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia (FH) with different allele grades. Methods: Patients with FH phenotype, who admitted to Beijing Anzhen Hospital from January 2019 to October 2020, were enrolled. Age, sex and other clinical information were collected from enrolled, and the pathogenic genes were detected by the second generation sequencing technique. The patients were divided into five groups according to the number of alleles involved and the degree of gene damage: single allele-null mutation group, single allele-defect mutation group, multi-allele-null mutation group, multi-allele-defect mutation group and no major pathogenic gene mutation group. The results of blood lipids were collected before medication, 4-6 weeks of intensive statin treatment and one month after combined treatment with PCSK9 inhibitor (PCSK9i). The LDL-C level were compared among groups. ASCVD risk stratification was performed in all patients, and the proportion of LDL-C level reaching the corresponding risk stratification target value of each genotype group after treatment was analyzed. Results: A total of 66 patients with FH phenotype were included, including 47 males (71.2%) and 19 females (28.8%),the mean age was(43.1±13.4 years). There were 7 cases in single allele-null mutation group (10.6%), 25 cases in single allele-defect mutation group (37.9%), 8 cases in multi-allele-null mutation group (12.1%), 18 cases in multi-allele-defect mutation group (27.3%) and 8 cases in no major pathogenic mutation group (12.1%). The degree of LDL-C reduction post combined PCSK9 inhibitor therapy was as follows: single allele mutation group>no major pathogenic mutation group>multi-allele mutation group, general distribution was in the range of 0-90.0%. Two groups of single allele mutation and no major pathogenic mutation group>50.0%>multi-allele mutation group. Under the combined treatment of PCSK9 inhibitors, the further decrease of LDL-C was in the order of single allele mutation group>non-major pathogenic mutant group>multi-allele mutation group. The efficacy of combined therapy on reducing LDL-C at 1 month after treatment decreased with the increase of baseline LDL-C level (r = 0.46, P<0.001) in patients with FH phenotype. In addition, the further decrease of LDL-C level post high-intensity statin therapy combined with PCSK9 inhibitors decreased with the increase of baseline LDL-C levels (r = 0.40, P<0.001). The degree of LDL-C decrease was high and stable by statin combined with PCSK9 inhibitor therapy in single allele mutation group. In the single allele-defect mutant group, the decrease of LDL-C increased with the increase of baseline LDL-C level post intensive statin treatment and combined PCSK9 inhibitor treatment ((r=0.54, P=0.009); r=0.45,P=0.030), and the further decrease of LDL-C level decreased with the increase of baseline LDL-C level in single allele-defect mutant group post combined therapy with PCSK9 inhibitor (r=0.43, P=0.040). The decrease of LDL-C in patients with the multi-allele mutation group varied with different pathogenic gene loci and combinations post combined therapy with PCSK9 inhibitor. There was no significant difference in the level of blood lipids between the group without major pathogenic gene mutation and the group with single allele mutation before and after treatment. The percentage of patients achieving LDL-C goals with different genotypes of phenotypic FH were as follows: single allele mutation group (86.7%), non-major pathogenic mutant group (75.0%) and multi-allele mutation grou (<5.0%). Conclusions: All patients with different FH phenotypes could benefit from the intensive lipid-lowering therapy with statins and PCSK9 inhibitors, however, there are significant differences in the efficacy of lowering LDL-C in Chinese patients with FH phenotype with different molecular etiologies. Therefore, the pathogenic gene analysis may suggest the lipid-lowering effect of PCSK9 inhibitors in patients with FH.


Subject(s)
Adult , Female , Genotype , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipoproteinemia Type II/genetics , Male , Middle Aged , Proprotein Convertase 9/genetics
20.
Article in Chinese | WPRIM | ID: wpr-888154

ABSTRACT

Magnoliae Officinalis Cortex(Houpo) can treat peptic ulcer disease(PUD), the mechanism of which remains unclear. In this study, network pharmacology and molecular docking were employed to predict the mechanism of Houpo in the treatment of PUD. Through literature review and TCMSP screening, 15 main active ingredients were obtained. The SwissTargetPrediction database was used to predict the potential targets of the ingredients, and Therapeutic Target Database(TTD), DrugBank, and Human Phenotype Ontology(HPO) to screen the disease-related targets. A total of 49 potential targets were obtained by the intersection of active ingre-dients-related targets and disease-related targets. Cytoscape 3.6.1 was employed to construct the protein-protein interaction network for the targets with high confidence(score>0.700) screened out by STRING. The DAVID database was used for GO and KEGG pathway enrichment of potential targets. GO enrichment analysis showed that the treatment mechanism was mostly related to nuclear receptor activity, ligand-activated transcription factor activity, and G protein-coupled acetylcholine receptor activity. KEGG enrichment analysis found that Houpo could regulate material metabolism, endocrine system, p53 signaling pathway, and PPAR signaling pathway. Molecu-lar docking verified that all 15 ingredients had good binding activities with key targets(CHRM1, CHRM2, FABP1, mTOR, and STAT3). The results mean that Houpo can treat PUD by participating in cell metabolism, inhibiting inflammatory cytokines, and regulating cell proliferation and apoptosis.


Subject(s)
Drugs, Chinese Herbal , Humans , Molecular Docking Simulation , Peptic Ulcer , Protein Interaction Maps , Receptor, Muscarinic M1 , Signal Transduction
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