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1.
Article in Chinese | WPRIM | ID: wpr-943090

ABSTRACT

ObjectiveTo evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang. MethodSixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks. The primary outcome indicator was change in forced vital capacity (FVC) from the baseline, and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity (FVC%pred), percentage of forced expiratory volume in first second to predicted value (FEV1%pred), King's Brief Interstitial Lung Disease (K-BILD) total score, 6 minute walking distance (6MWD), hydroxyproline (HYP), matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and transforming growth factor-β (TGF-β) from baseline. Patients in line with the inclusion criteria were included in the primary analysis, and sensitivity analysis was performed after multiple imputation of missing data. Safety set was adopted for safety analysis. ResultThe 66 patients (included in the sensitivity analysis) meeting the inclusion criteria included 34 in the observation group and 32 in the control group, and 60 patients finally received the whole trial intervention (included for primary analysis). Compared with the baseline, the FVC increased in the observation group and decreased in the control group after intervention (P<0.01), which was consistent between the sensitivity analysis and the primary analysis. The changes in FVC%pred, FEV1%pred, 6MWD, and K-BILD total score from baseline in the observation group were superior to those in the control group (P<0.01), with consistent results between the sensitivity analysis and the primary analysis. TIMP-1 in the observation group decreased compared with baseline (P<0.05), while TIMP-1 in the two groups showed no significant changes from the baseline The observation group outperformed the control group in the changes in HYP, MMP-9, and TGF-β from baseline (P<0.05). The common adverse events were cough, diarrhea, nausea, rash, and upper gastrointestinal tract infection, the incidence of which showed no statistical difference between the two groups. ConclusionBuyang Huanwutang can improve lung function, motor function, and quality of life in patients with connective tissue disease-associated pulmonary fibrosis and has good safety. The mechanism may be related to the reduction of TGF-β, MMP-9, and TIMP-1 levels and maintaining of MMP-9/TIMP-1 balance.

2.
Acta Pharmaceutica Sinica ; (12): 2857-2863, 2022.
Article in Chinese | WPRIM | ID: wpr-941501

ABSTRACT

In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of 1H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.

3.
Article in Chinese | WPRIM | ID: wpr-940990

ABSTRACT

OBJECTIVE@#To analyze the long-term trends of the changes in the equity of China's health workforce allocation to provide a reference for the more balanced and orderly development of China's health system.@*METHODS@#The Gini coefficient was used to evaluate the degree of equity in the allocation of health workforce between regions, and the Gini coefficients for the allocation of doctors and nurses based on population and regional gross domestic product (GDP) distribution were calculated respectively.@*RESULTS@#In 2019, the number of licensed (assistant) physicians per 1 000 population in China was 2.77, and the number of registered nurses per 1 000 population was 3.18. The Gini coefficient for the distribution of licensed (assistant) physicians by population was 0.141 in 2002, decreasing to 0.081 by 2014 and then remained stable. The Gini coefficient for the distribution of registered nurses by population was 0.164 in 2002 and decreased to 0.066 in 2018. The Gini coefficient for the distribution of licensed (assistant) physicians by GDP was 0.236 in 2002, decreased to 0.169 in 2013, then increased to 0.183 and remained stable. The Gini coefficient for the distribution of registered nurses by GDP was 0.206 in 2002, decreased to 0.150 in 2013, and then increased each year to 0.180 in 2019. The equity of the allocation of registered nurses by population was worse than the equity of the allocation of licensed (assistant) physicians in 2002, and in 2016, for the first time, exceeded that of licensed (assistant) physicians.@*CONCLUSION@#Equity in the allocation of health workforce across China has improved, but the improvement in equity between regions has hit a bottleneck, with health workforce allocation in the western regions still relatively scarce. Although nursing workforce allocation equity caught up with licensed (assistant) physicians, the number of licensed (assistant) physicians is close to that of developed western countries, while there is a large gap in registered nurses. It is recommended that the relevant authorities make good long-term planning for health workforce, further increase the policy for the introduction of health workforce in the western region, and increase the supply of healthcare services in the western region with the help of digital transformation of healthcare and internet healthcare. At the same time, they should further increase investment in resources for higher nursing education and actively plan to cope with the ageing population.


Subject(s)
China , Health Equity , Health Services , Health Workforce , Humans , Workforce
4.
Article in Chinese | WPRIM | ID: wpr-940986

ABSTRACT

OBJECTIVE@#To evaluate the effectiveness of statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases by the Western guidelines in a community-based Chinese population from economically developed areas using data from the Chinese electronic health records research in Yinzhou (CHERRY) study.@*METHODS@#A Markov model was used to evaluate the effectiveness of the following statin treatment strategies, including: (1) usual care without cardiovascular risk assessment(Strategy 0); (2) using the World Health Organization (WHO) non-laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 1); (3) using the WHO laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 2); and (4) using the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) model with statin treatment for high-risk group (risk ≥ 10%, Strategy 3). According to the guidelines, adults in the medium-risk group received lifestyle intervention, and adults in the high-risk group received life-style intervention and statin treatment under these strategies. The Markov model simulated different strategies for ten years (cycles) using parameters from the CHERRY study, published data, meta-analyses and systematic reviews for Chinese. The number of cardiovascular events or deaths, as well as the number need to treat (NNT) with statin per cardiovascular event or death prevented, were calculated to compare the effectiveness of different strategies. One-way sensitivity analysis on the uncertainty of incidence rate of cardiovascular diseases, and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#Totally 225 811 Chinese adults aged 40-79 years without cardiovascular diseases at baseline were enrolled. In contrast to the usual care without risk assessment-based statin treatment strategy, Strategy 1 using the WHO non-laboratory-based risk charts could prevent 3 482 [95% uncertainty interval (UI): 2 110-4 661] cardiovascular events, Strategy 2 using the WHO laboratory-based risk charts could prevent 3 685 (95%UI: 2 255-4 912) events, and Strategy 3 using the China-PAR model could prevent 3 895 (95%UI: 2 396-5 181) events. NNTs with statin per cardiovascular event prevented were 22 (95%UI: 14-54), 21 (95%UI: 14-52), and 27 (95%UI: 17-67), respectively. Strategy 3 could prevent more cardiovascular events, while Strategies 1 and 2 required fewer numbers need to treat with statin per cardiovascular event prevented. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases recommended by the Western guidelines could achieve substantive health benefits in adults from developed areas of China. Using the China-PAR model for cardiovascular risk assessment could prevent more cardiovascular diseases while using the WHO risk charts seems more efficient.


Subject(s)
Adult , Cardiovascular Diseases/prevention & control , China/epidemiology , Cost-Benefit Analysis , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Primary Prevention
5.
Article in English | WPRIM | ID: wpr-937807

ABSTRACT

Background@#and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). @*Methods@#This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. @*Results@#The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. @*Conclusions@#IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.

6.
Article in Chinese | WPRIM | ID: wpr-934367

ABSTRACT

Objective:To establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy based on machine learning algorithms.Methods:Retrospective study adopted,from 2019 to 2020,260 patients were referred to the Department of Nephrology at the First Affiliated Hospital of Kunming Medical University, the First People′s Hospital in Yunnan province, and Yan′an Hospital of Kunming city. All patients were diagnosed by renal pathology, 130 cases of primary IgA nephropathy, the 130 cases of non-IgA nephropathy. Collection of materials, including gender and age, 28 clinical data, and routine laboratory test results,the sex ratio of IgA nephropathy group and non-IgA nephropathy group were 59∶71 and 64∶66 respectively, the ages were 37.20 (21.89, 53.78) and 43.30 (27.77, 59.18) years, respectively. 260 patients were divided into a training set (70%, 182 cases) and a test set (30%, 78 cases). Using the decision tree, random forests, support vector machine, extreme gradient boosting to establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy. Based on the true positive rate, true negative rate, false-positive rate, false-negative rate, accuracy, subjects features work area under the curve(AUC), the precision ratio, recall ratio, and F1 score, comprehensively evaluate the performance of each model, finally, the best performance of the model was chosen. Using SPSS 25.0 to analyze the data, P<0.05 was considered to be statistically significant. Results:The accuracy of the decision tree, support vector machine, random forests and extreme gradient boosting establish differential diagnosis model was 67.95%, 70.51%, 80.77% and 83.33%, respectively; AUC values was 0.74, 0.76, 0.80 and 0.83; Judgment for primary IgA nephropathy F1 score was 0.73, 0.72, 0.80 and 0.83, respectively. The efficiency of the extreme gradient boosting model based on the above evaluation indicators is the highest, its diagnosis of IgA nephropathy of the sensitivity and specificity respectively 89% and 79%. The variable importance from high to low was blood albumin, IgA/C3, serum creatinine, age, urine protein, urine albumin, high-density lipoprotein cholesterol, urea.Conclusion:The differential diagnosis model for IgA nephropathy was established successfully and non-IgA nephropathy and the efficiency performance of the extreme gradient boosting algorithm was the best.

7.
Acta Pharmaceutica Sinica ; (12): 343-352, 2022.
Article in Chinese | WPRIM | ID: wpr-922910

ABSTRACT

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

8.
Acta Pharmaceutica Sinica ; (12): 593-603, 2021.
Article in Chinese | WPRIM | ID: wpr-873771

ABSTRACT

The therapeutic effect of tumor photodynamic therapy is severely limited by the hypoxic tumor microenvironment. Inhibiting tumor celloxygen consumption is a more effective way than increasing its oxygen supply to overcome the tumor hypoxia and enhance photodynamic therapy. To carry out this strategy, the supramolecular nanoparticles VER-ATO-SMN loaded with photosensitizer verteporfin (VER), oxygen-consuming inhibitor atovaquone (ATO), and stabilizer polyvinylpyrrolidone (PVP)-K30 were prepared by the nanoprecipitation method, and the optimal prescription was screened and optimized by single factor experiments. The results showed that the optimal prescription for VER-ATO-SMN was ATO∶VER (w/w) = 1∶1, PVP-K30 = 100 mg, N,N-dimethylformamide∶water (v/v) = 1∶10. The morphology, particle size, particle dispersion index and encapsulation efficiency of supramolecular nanoparticles were characterized. The VER-ATO-SMN showed a spherical morphology and was well dispersed. The hydrodynamic size of VER-ATO-SMN was 101.21 ± 4.30 nm as determined by dynamic light scattering (DLS). The encapsulation efficiencies of VER and ATO in VER-ATO-SMN prepared with the optimal prescription were 70.86% and 77.52%, respectively. The VER-ATO-SMN exhibited good laser stability and also showed high stability in conditions which simulated the physiological solution. Compared with free VER and VER liposome, VER-ATO-SMN performed enhanced therapeutic effect at the cell level. The mechanism was that VER-ATO-SMN could effectively incorporate into cells and improving the intracellular oxygen concentration by reducing the oxygen consumption of tumor cells could increase the amount of reactive oxygen species generated by VER mediated photodynamic therapy. The in vivo anticancer efficacy results of tumor-bearing mice suggested that VER-ATO-SMN could effectively inhibit the tumor growth or even completely eliminate the tumor. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of 900 Hospital of the Joint Logistics Team.

9.
Article in English | WPRIM | ID: wpr-890191

ABSTRACT

Objective@#The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer’s disease (AD) in Taiwan. @*Methods@#We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. @*Results@#During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. @*Conclusion@#We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

10.
Acta Pharmaceutica Sinica ; (12): 306-313, 2021.
Article in Chinese | WPRIM | ID: wpr-872611

ABSTRACT

To improve the efficacy of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT), a fluorocarbon microemulsion-based gel (FMBG) loaded with both 5-ALA and carbon dioxide (CO2) was prepared in this study. Its physical and chemical properties such as particle size, zeta potential, morphology, pH value and viscosity were characterized. Acid-base titration experiment was used to determine the CO2 loading, a fluorescence derivatization method was established to determine the content of 5-ALA, and the confocal laser scanning microscope and Franz diffusion cell method were carried out to investigate its transdermal ability. Through the laser speckle contrast imaging, the CO2-affected blood flow perfusion of skin was measured. Finally, the skin irritation test was tested by hematoxylin-eosin staining (H&E) method. These results showed that the prepared FMBG was a milky white gel, with an average particle size of 202.4 nm, a zeta potential of -25.3 mV, a pH of 6.0, and a viscosity of 1 062.0 mPa·s. It can be stored stably for seven days at room temperature. The 5-ALA content of FMBG was measured to be approximately equal to 20% (w/w). At room temperature and normal pressure, the CO2 loading content of FMBG was 5.016 mg·L-1, which was 1.5 times as much as that of water. The transdermal absorption experiment and blood perfusion results showed that the FMBG can effectively enable the transdermal delivery of 5-ALA and CO2, and significantly increased the blood perfusion of skin. H&E staining results indicated that FMBG had negligible skin irritation (all animal tests were approved by the Ethics Committee of 900 Hospital of the Joint Logistics Team). In this study, a safe and stable FMBG loaded with both 5-ALA and CO2 was successfully prepared. It was suitable for transdermal application, having the potential of enhancing the efficacy of 5-ALA-mediated PDT.

11.
Chinese Journal of Biotechnology ; (12): 3915-3932, 2021.
Article in Chinese | WPRIM | ID: wpr-921476

ABSTRACT

Targeted protein degradation (TPD) technology facilitates specific and efficient degradation of disease-related proteins through hijacking the two major protein degradation systems in mammalian cells: ubiquitin-proteasome system and lysosome pathway. Compared with traditional small molecule-inhibitors, TPD-based drugs exhibit the characteristics of a broader target spectrum. Compared with techniques interfere with protein expression on the gene and mRNA level, TPD-based drugs are target-specific, efficaciously rapid, and not constrained by post-translational modification of proteins. In the past 20 years, various TPD-based technologies have been developed. Most excitingly, two TPD-based therapeutic drugs have been approved by FDA for phase Ⅰ clinical trials in 2019. Despite of the early stage characteristics and various obstructions of the TPD technology, it could serve as a powerful tool for the development of novel drugs. This review summarizes the advances of different degradation systems based on TPD technologies and their applications in disease therapy. Moreover, the advantages and challenges of various technologies were discussed systematically, with the aim to provide theoretical guidance for further application of TPD technologies in scientific research and drug development.


Subject(s)
Animals , Proteasome Endopeptidase Complex/metabolism , Protein Processing, Post-Translational , Proteins/metabolism , Proteolysis , Technology
12.
Article in Chinese | WPRIM | ID: wpr-906322

ABSTRACT

The homology of medicine and food has long been recognized in China, and the medicinal and edible resources are often employed to prevent and treat diseases or maintain health in traditional Chinese medicine (TCM). Due to the unique geographical and climatic conditions, the Xinjiang Uygur Autonomous Region (hereinafter referred to as Xinjiang) is blessed with abundant medicinal and edible resources, like Rosae Rugosae Flos, Punica granatum, and Amygdalus communis, which have been widely used by local ethnic communities as medicine in light of the remarkable pharmacological activities, guaranteeing their health condition to some extent. This paper collected the relevant articles from China National Knowledge Infrastructure (CNKI) database through the keyword and full-text search with the medicinal and edible resource Rosae Rugosae Flos as the search term, and the subsequent analysis revealed that the medicinal and edible resources in Xinjiang has a wide range of applications in food, medicine, and ecological protection. This paper further explored their research value, status, and prospects, so as to provide some references for the rational, effective, and sustainable development and utilization of these medicinal and edible resources in Xinjiang, thus better achieving "poverty alleviation" and "rural revitalization", popularizing TCM culture, and building a healthy China.

13.
Article in Chinese | WPRIM | ID: wpr-906010

ABSTRACT

Xinjiang is rich in resources of medicinal plants, which are widely used in ethnic medicines because of their remarkable pharmacological activities and safeguard lives and health of people of all ethnic groups in Xinjiang and local health services. The ethnic medicines in Xinjiang are harmonious but different and united in diversity. Besides, they also promote each other and develop together, constituting an inseparable and important part of traditional Chinese medicine in China. Among them, Uygur medicine, Kazak medicine, Kirgiz medicine, Tajik medicine, and Tatar medicine are predominant in regional characteristics, but the development of the ethnic medicine industry in Xinjiang is backward. In recent years, Xinjiang ethnic medicines have been reported to possess significant pharmacological activities, which deserve further development and investigation. However, the development of ethnic medicines in Xinjiang has been restricted severely due to the lack of effective inheritance of practice and experience, weak basic research, insufficient brand awareness, resource destruction, etc. This study analyzed the medicinal value, development status, and prospects of Xinjiang ethnic medicines and summarized the problems in the modernization of ethnic medicines in Xinjiang to provide some scientific references for the follow-up development and clinical application of Xinjiang ethnic medicines, aiming to promote the sustainable development of traditional ethnic medicines of China.

14.
Article in English | WPRIM | ID: wpr-899144

ABSTRACT

Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

15.
Article in English | WPRIM | ID: wpr-897895

ABSTRACT

Objective@#The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer’s disease (AD) in Taiwan. @*Methods@#We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. @*Results@#During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. @*Conclusion@#We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

16.
Article in English | WPRIM | ID: wpr-891440

ABSTRACT

Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

17.
Article in Chinese | WPRIM | ID: wpr-879025

ABSTRACT

To prove that ursolic acid(UA)could activate the autophagy of colorectal cancer HCT116 cells by inhibiting hedgehog signaling pathway. The effect of UA on the viability of HCT116 cells was determined by MTT assay. The effect of UA on the proliferation and migration of HCT116 cells was detected by crystal violet staining and scratch test. In the study on autophagy, the time points were screened out first: the autophagy fluorescence intensity of UA acting on HCT116 at different time points were detected by Cell Meter~(TM) Autophagy Assay Kit; Western blot was used to detect the expression of autophagy protein P62 at different time points. Then, Cell Meter~(TM) Autophagy Assay Kit was used to detect the effect of UA on autophagy fluorescence intensity of HCT116 cells. The effect of different doses of UA on the expressions of LC3Ⅱ and P62 proteins in HCT116 cells were detected by Western blot. Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3Ⅱ by Western blot. In terms of mechanism, the effect of UA on hedgehog signaling pathway-related proteins in HCT116 cells was detected by Western blot. The results showed that UA inhibited the activity, proliferation and migration of HCT116 cells. UA enhanced the fluorescence intensity of autophagy in HCT116 cells, while promoting the expression of LC3Ⅱ and inhibiting the expression of P62, in a time and dose dependent manner. UA activated the autophagy in HCT116 cells, which manifested that UA resulted in the accumulation of fluorescence spots and strengthened the fluorescence intensity of autophagosomes; compared with UA alone, UA combined with autophagy inhibitor CQ promoted the expression of LC3Ⅱ. UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.


Subject(s)
Apoptosis , Autophagy , Cell Line, Tumor , Colorectal Neoplasms , Hedgehog Proteins/genetics , Humans , Signal Transduction , Triterpenes
18.
Article in Chinese | WPRIM | ID: wpr-909619

ABSTRACT

OBJECTIVE To investigate the pharmacological effect of ursolic acid (UA) on colitis-associated colorec?tal cancer (CAC) and its underlying mechanism based on the Wnt signaling pathway. METHODS The CAC model in mice was established by azoxymethane (AOM) combined and dextran sulfate sodium salt (DSS), accompanied by treat?ment with various dosages of UA and concomitant appraisal of body weight, stool and physical state of the mice. After the sacrifice of the mice, the tumor and length of the colorectum were measured, followed by retrieval of the liver, spleen, thymus and tumor tissue for downstream assays. The levels of inflammatory factors interleukin-6 (IL-6), IL-1βand C-reactive protein (CRP) in the tumor and serum were examined by enzyme-linked immunosorbent assay (ELISA). The pathological changes of colorectal tissues were observed by HE staining. The levels in tumors of Wnt/β-catenin sig?naling pathway-related proteins Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry (IHC). The mRNA expressions of Wnt4, GSK-3β,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, Bax, caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR (RT-qPCR). The protein levels of Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, phospho-β-catenin, phospho-GSK-3β, Bcl-2 and Bax in tumors were probed by analyzed by Western blotting (WB). Also, RNA-seq was employed to assess the gut microbiota in the mice. RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC, evidenced by improved physical state, body weight, survival rate, colorectal length, the mass of liver, thy?mus, spleen, and decreased CAC load and colorectal mass. UA attenuated the levels of IL-6, IL-1β and CRP in the mouse serum and colorectal tumor in a dose-dependent manner. HE staining showed that UA lessened carcinogenesis in the colorectum, with lower infiltration of lymphocytes, versus the control. IHC indicated that UA mitigated the expres?sion of Wnt4,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and promoted the GSK-3βexpression, compared with the control. Furthermore, UA diminished the mRNA expressions of Wnt4, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and heightened the mRNA levels of GSK-3β, caspase-3, capase-9 and Bax in CAC. The results of mRNA expressions were verified by WB analysis, which revealed that UA impeded the protein expression of Wnt4,β-catenin, c-Myc, cyclin D1, Bcl-2, TCF4, LEF1, and elevated the protein levels of GSK-3βand Bax, phospho-β-catenin in mouse CAC. In addi?tion, UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC. CONCLU?SION Ursolic acid may protect against CAC, potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

19.
Article in Chinese | WPRIM | ID: wpr-909613

ABSTRACT

OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro. METHODS MTT colorimetric method was used to detect the influence of scutellar?in on the survival rate of HCT116 cells. And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy. Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells. Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells. Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signal?ing pathway-related proteins Mst1, Lats1, YAP1, p-YAP(Ser127), TAZ, and its downstream effector proteins c-Myc and cyclin D1, as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells. RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells. Hoechst33342/PI double stain?ing showed that scutellarin effectively induced the apoptosis of HCT116 cells. Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1, Lats1, YAP1, TAZ and its downstream effector pro?teins c-Myc, cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin, and the expression of p-YAP (ser127) was up-regulated. Moreover, scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2, and promoted the protein level of Bax. CONCLUSION Scutellarin may inhibit the proliferation and migra?tion of HCT116 cells, while induce its apoptosis, potentially by activation of Hippo signaling pathway.

20.
Article in Chinese | WPRIM | ID: wpr-909607

ABSTRACT

OBJECTIVE To investigate the inhibition and mechanism of berberine on human colorectal cancer HCT116 cells through canonical Hedgehog signaling pathway. METHODS The effect of berberine on cell morphology was observed by microscopy. MTT colorimetric assay, cell scratch experiment, colony formation assay and Hoechest/PI staining were utilized to detect the activities of berberine on cell viability, cell migration and cell apoptosis. Flow cytome?try was applied to examine the cell apoptosis. The effects of berberine on caspase-3 and caspase-9 were detected by caspase activity detection kit. The expressions of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related proteins Bax and Bcl-2 as well as cell cycle-related proteins cyclin D1 were detected by Western blotting. Additionally, quantitative real time RT-PCR was employed to assess the mRNA expression levels of Hedgehog signaling pathway-related genes SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related genes Bax and Bcl-2 as well as cell cycle-related genes cyclin D1. RESULTS Berberine sharply altered the morphology of human colorectal cancer HCT116 cells, demonstrated by that migration ability of HCT116 cells was reduced significantly and the nuclei were densely stained. Berberine could induce apoptosis in a dose-dependent manner. The activities of caspase-3 and caspase-9 were increased prominently. The expression levels of Hedgehog signaling pathway-related protein SUFU and apoptosis-related protein Bax were augmented substantially. The expression levels of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, apoptosis-related protein Bcl-2 as well as cell cycle-related genes cyclin D1 were markedly lessened. Besides, the mRNA expression levels of Hedgehog signaling pathway-related gene SUFU and apoptosis-related gene Bax were augmented substantially. The mRNA expression levels of Hedgehog signaling path?way-related genes SHH, GLI1, PTCH1, SMO, apoptosis-related gene Bcl-2 as well as cell cycle-related gene cyclin D1 were markedly lessened. CONCLUSION Berberine, which is the main component of coptidis rhizoma, can remarkably restrain the growth and proliferation, promote apoptosis of human colorectal cancer cells HCT116, and the underlying mechanism may be involved in suppressing the activity of the Hedgehog signaling pathway.

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