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1.
Acta Pharmaceutica Sinica B ; (6): 87-109, 2024.
Article in English | WPRIM | ID: wpr-1011232

ABSTRACT

The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent Mpro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent Mpro inhibitors with desirable properties have been developed based on available crystal structures of Mpro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent Mpro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent Mpro inhibitors are also discussed.

2.
International Eye Science ; (12): 1811-1815, 2023.
Article in Chinese | WPRIM | ID: wpr-996889

ABSTRACT

The occurrence and development of many eye diseases are closely related to genetic and environmental factors, among which epigenetic modification is an important bridge connecting genetic and environmental factors. It can affect the levels of related genes by influencing gene transcription or translation, thereby playing a role in the pathogenesis of ocular diseases. DNA methylation is an important part of epigenetic modification which is usually regulated by three processes: de novo methylation, maintenance methylation, and demethylation, and plays an essential role in regulating gene expression. At present, researchers have conducted that DNA methylation plays an important role in repair of damage to corneal endothelium, mitochondrial dynamics regulation and diabetic retinopathy, oxidative stress response and cataracts and other eye diseases, providing new ideas in the treatment of related ocular diseases. This study presented a brief review of the role of DNA methylation in the development of related ocular diseases and provided new perspectives and directions for the screening, diagnosis, and treatment of eye diseases.

3.
China Pharmacy ; (12): 1165-1171, 2023.
Article in Chinese | WPRIM | ID: wpr-973613

ABSTRACT

OBJECTIVE To explore standardized evaluation process for clinical comprehensive evaluation of blood lipid- regulating drugs and perform rapid assessment of clinical comprehensive evaluation of blood lipid-regulating drugs with different mechanisms so as to provide reference for the drug catalogue selection and rational drug use of medical institutions. METHODS Referring to guidelines and consensus such as the guideline for the management of comprehensive clinical evaluation of drugs, the methods such as literature research, expert interviews, and Delphi expert consultation were used to establish a multi-dimensional and multi-criteria clinical comprehensive evaluation index system and quantitative scoring table for blood lipid-regulating drugs around the two main lines of technical evaluation and policy evaluation. Then 13 blood lipid-regulating drugs with different mechanisms in 21 third-grade class-A medical institutions from five provinces and regions of Northwest China were scored from both technical and policy dimensions to form a comprehensive evaluation result. RESULTS The clinical comprehensive evaluation index system and corresponding rapid evaluation quantitative scoring table were constructed for blood lipid-regulating drugs in the five northwest provinces and regions. The technicalevaluation section included 6 primary indicators, 13 secondary indicators, and 34 tertiary indicators, totaling 110 points. The policy evaluation section included 4 primary indicators and 6 secondary indicators, with a total score of 40 points (30 points for some drugs) and a total score of 150 points (or 140 points). The scoring results showed that the highest score was atorvastatin, followed by rosuvastatin and simvastatin. CONCLUSIONS Statins are still the cornerstone of drug therapy for patients with dyslipidemia; the rapid evaluation quantitative scoring table constructed in this study is comprehensive, systematic and operable. The evaluation process in this study can provide empirical references for other groups to exploring the standardized path and quality control mechanism of clinical comprehensive evaluation of drugs.

4.
China Pharmacy ; (12): 1159-1164, 2023.
Article in Chinese | WPRIM | ID: wpr-973612

ABSTRACT

OBJECTIVE To provide reference for the subsequent landing of national medical insurance negotiated drugs (referred to as “national negotiated drugs”) at the provincial level. METHODS By reviewing the data publicly released by the official websites of National Healthcare Security Administration and the Healthcare Security Administration of Zhejiang Province, combined with policy documents, the descriptive analysis was conducted on the number of tertiary medical institutions, the actual allocation of national negotiated drugs, the availability rate of national negotiated drugs, the allocation rate of national negotiated drug varieties, and the allocation rate of medical institutions of various cities in Zhejiang province. The Spearman rank correlation test was used to analyze the correlation between the number of types of national negotiated drugs equipped in tertiary medical institutions in Zhejiang province and the per capita disposable income, the number of tertiary medical institutions equipped with national negotiated drugs, and the implementation time of disease diagnosis-related grouping (DRG) of various cities in Zhejiang province. RESULTS As of the first quarter of 2022, 135 tertiary medical institutions in Zhejiang province were equipped with a total of 261 types of national negotiated drugs, accounting for 94.91% of the 2021 edition of the National Negotiated Drugs Catalogue (275 types). The allocation rates of Goserelin acetate sustained-release implant, Sacubitril valsartan sodium tablets, Alteplase for injection and other varieties were at high level, and the types of national negotiated drugs equipped were highly coincident with the top 10 causes of death with disease of urban and rural residents in Zhejiang province. The tertiary medical institutions in Hangzhou had the most types of national negotiated drugs, with 230 types, while Quzhou had the lowest, with only 34 types; allocation rate of national negotiated drugs in medical institutions of Zhoushan was the highest (100%), while that of Lishui was the lowest (57.14%). The types of national negotiated drugs equipped were positively correlated with per capita disposable income in various cities and the number of tertiary medical institutions equipped with national negotiated drugs (P<0.01), and there was no significant correlation with the length of implementation of DRG (P>0.05). CONCLUSIONS mail:lanyao@mails.tjmu.edu.cn The landing of national negotiated drugs in Zhejiang province is generally good, with a high rate of equipping tertiary medical institutions with national negotiated drugs and a high rate of equipping drug varieties. Therefore, it is recommended that the provincial implementation of national negotiated drugs should be multi-faceted, and policy-making departments should adopt a dual-channel of “unbundling” and “driving” to smooth the drug chain into hospitals. The health insurance sector should improve the “dual channel” management mechanism to share the pressure on hospitals to use drugs. At the same time, it should also improve the multi-level medical security system and raise the level of reimbursement of medical insurance for national negotiated drugs.

5.
China Journal of Chinese Materia Medica ; (24): 1731-1738, 2023.
Article in Chinese | WPRIM | ID: wpr-981390

ABSTRACT

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.


Subject(s)
Humans , Medicine, Chinese Traditional , Ulcer , Vascular Endothelial Growth Factor A/metabolism , Diabetes Complications/drug therapy , Wound Healing/physiology , Diabetes Mellitus
6.
China Journal of Chinese Materia Medica ; (24): 1724-1730, 2023.
Article in Chinese | WPRIM | ID: wpr-981389

ABSTRACT

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.


Subject(s)
Humans , Ulcer/therapy , Medicine, Chinese Traditional , Beclin-1 , Quality of Life , Wound Healing , Diabetes Complications , Autophagy , Diabetic Foot/drug therapy , Diabetes Mellitus/genetics
7.
Biomedical and Environmental Sciences ; (12): 903-916, 2023.
Article in English | WPRIM | ID: wpr-1007865

ABSTRACT

OBJECTIVE@#To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR).@*METHODS@#Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting.@*RESULTS@#Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.@*CONCLUSION@#Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.


Subject(s)
Humans , Aurora Kinase A/metabolism , Cell Line, Tumor , Mitosis , Cell Cycle , Radiation, Ionizing , RNA, Small Interfering/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism
8.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 227-235, 2022.
Article in Chinese | WPRIM | ID: wpr-940607

ABSTRACT

Benign prostatic hyperplasia (BPH) model, as a carrier of BPH, is vital for exploring the pathogenesis of the disease and evaluating the efficacy of corresponding drugs. This paper reviewed the in vivo and in vitro models of BPH, the modeling principles and methods, and evaluation indicators, and analyzed the advantages and disadvantages of different types of models. At present, the BPH model is getting closer to the clinical characteristics of human BPH, providing powerful support for the evaluation of drug efficacy. Furthermore, the model has been developed towards cytology to allow further research on the pathogenesis of BPH. The relevant testing indicators reflect the core pathological changes of BPH from different levels, providing a guarantee for further exploring the pathogenesis of BPH and the development of prevention and control drugs. However, no model can fully simulate the natural development process of human BPH, and each model and evaluation criterion has its unique advantages and limitations. In terms of model evaluation, most BPH models are assessed based on benign prostate enlargement (BPE), and there is still a lack of reliable models to simulate BPH progression and combine with bladder dysfunction. In terms of indicator evaluation, symptom-reflected behavioral indicators are absent in the replication of BPH models in animals. The study of the BPH model in traditional Chinese medicine (TCM) only focuses on the replication and investigation of the "disease" model, rather than the "syndromes" and "signs", which cannot simulate the syndrome differentiation and treatment under the guidance of the TCM theory. In view of the above deficiencies, we should further improve the modeling method based on clinical characteristics, explore the multifactor composite models, especially those of disease-syndrome combination suitable for basic research of TCM, replicate the model closing to disease development, and optimize the evaluation indicators, which is of great theoretical and practical significance to develop drugs for effective prevention and control of BPH.

9.
Biomedical and Environmental Sciences ; (12): 437-447, 2022.
Article in English | WPRIM | ID: wpr-927682

ABSTRACT

Objective@#miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT).@*Methods@#TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified.@*Results@#Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation.@*Conclusion@#Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.


Subject(s)
Down-Regulation , Epithelial-Mesenchymal Transition , Epithelium/metabolism , MicroRNAs/metabolism , Transforming Growth Factor beta1/pharmacology
10.
Biomedical and Environmental Sciences ; (12): 419-436, 2022.
Article in English | WPRIM | ID: wpr-927681

ABSTRACT

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.


Subject(s)
Humans , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/metabolism , Cell Line, Tumor , DNA/therapeutic use , Glioblastoma/metabolism , Radiation, Ionizing , Temozolomide/therapeutic use
11.
Chinese Herbal Medicines ; (4): 342-350, 2021.
Article in Chinese | WPRIM | ID: wpr-953641

ABSTRACT

Objective: To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases. Methods: The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein–protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms. Results: The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of de novo fatty acids synthesis, anti-inflammation and anti-oxidation. Conclusion: This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.

12.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 145-152, 2021.
Article in Chinese | WPRIM | ID: wpr-905875

ABSTRACT

Objective:The biological mechanism of <italic>Codonopsis pilosula</italic> adaptation to drought was explored by determining the root metabolome of <italic>C. pilosula</italic> during harvesting. Method:Non-targeted metabonomics LC-MS was used to screen differential metabolites by multivariate statistical analysis,univariate statistical analysis and metabolic pathway enrichment analysis. Result:①There were 274 metabolites in LD vs CK group,142 of which were up-regulated and 132 of which were down-regulated. There were 284 metabolites with significant difference in MD vs CK group,of which 157 were up-regulated and 127 were down-regulated. There were 317 metabolites with significant difference in SD vs CK group,of which 133 were up-regulated and 184 were down-regulated. ②Differential metabolites were annotated into kyoto Encyclopedia of Gene and Genomes (KEGG) database and 82 differential metabolic pathways were obtained,among which sphingolipids metabolism was significantly enriched (<italic>P</italic><0.01).Metabolism of arginine and proline,tryptophan,alanine,galactose,nicotinic acid and nicotinamide,cysteine and methionine,arachidonic acid,linolenic acid and glycerides were significantly enriched in different metabolite pathways (<italic>P</italic><0.05). ③The metabolites of the three comparison groups before and after enrichment were classified and analyzed. It was found that they were mainly concentrated in fatty acyls group,carboxylic acid and derivatives,and organ oxygen compounds,followed by sphingolipids,indoles and derivatives,organonitrogen compounds,glycerophospholipids,pyridines and derivatives,peptidomimetics,glycerolipids and so on.In the drought stress of <italic>C. codonopsis</italic>,carbohydrate related metabolites were mainly up-regulated,lipid related metabolites were mainly down-regulated,and all other metabolites were up-regulated. Conclusion:The changes of metabolites in the roots of <italic>C. pilosula</italic> under drought stress were elucidated. carbohydrate and lipid-related metabolites were the main products of <italic>C. pilosula</italic> under drought stress,and these metabolites may be the main reason to improve the ability of <italic>C. pilosula</italic> to resist drought,which laid a foundation for further study on the mechanism of <italic>C. pilosula</italic> to resist drought.

13.
Journal of International Oncology ; (12): 302-307, 2021.
Article in Chinese | WPRIM | ID: wpr-882537

ABSTRACT

The incidence rate of biliary tract cancer is increasing year by year. Systemic therapy is the most important treatment for patients with advanced or unresectable biliary tract cancer. Gemcitabine combined with cisplatin is still the standard first-line chemotherapy, while gemcitabine combined with TS-1 and gemcitabine combined with nab-paclitaxel are also the first-line treatment options. Studies have confirmed that immunotherapy as a back-line treatment has a significant advantage in survival, and the disease control rate of nivolumab is 61% and the median overall survival is more than 1 year. In addition, targeted drugs targeting FGFR2, IDH1/2, HER-2 and other major driving genes of biliary tract cancer also show good antitumor activity, and become research hotspots in the treatment of advanced biliary tract cancer. Summarizing the research progress of systematic chemotherapy, immunotherapy and molecular targeted therapy for advanced biliary tract cancer can provide help for clinical practice.

14.
Chinese Acupuncture & Moxibustion ; (12): 1113-1117, 2021.
Article in Chinese | WPRIM | ID: wpr-921019

ABSTRACT

OBJECTIVE@#To explore the temperature field distribution and variation rules during treatment with mild moxibustion and sparrow-pecking moxibustion of TCM.@*METHODS@#Six healthy subjects were selected. Mild moxibustion and sparrow-pecking moxibustion were exerted at Zusanli (ST 36) respectively, for 25 min. Using infrared thermal imaging instrument, the temperature field distribution was measured during moxibustion at Zusanli (ST 36). The simulated thermometer was adopted to measure the temperature field distribution during moxibustion at the imitated cortex. At 20 min of mild moxibustion and sparrow-pecking moxibustion, the temperature field distribution generated by moxibustion was observed at the imitated cortex and Zusanli (ST 36) separately. The temperature values were collected at the sites 0.7, 2.1 and 3.5 cm far from the center of the moxibustion-exerted places successively, and then the characteristics of temperature field distribution and variation rules were compared between different moxibustion methods at the imitated cortex and Zusanli (ST 36).@*RESULTS@#At 20 min of mild moxibustion and sparrow-pecking moxibustion at Zusanli (ST 36), the temperature field distribution focused on the center of moxibustion-exerted site and the temperature was reduced to all directions and illustrated as a curved surface graph, whereas, the temperature field distribution at the imitated cortex was consistent with that at Zusanli (ST 36). With mild moxibustion, the temperature field was distributed uniformly along the longitudinal temperature gradient; whereas, with sparrow-pecking moxibustion, the longitudinal temperature of the temperature field was greatly different, in which, the maximum temperature and the average temperature were higher than those with mild moxibustion respectively and the first time up to the peak value of sparrow-pecking moxibustion was shorter than that with mild moxibustion. The thermal transfer was presented at the non-moxibustion exerted areas during the moxibustion experiment at Zusanli (ST 36).@*CONCLUSION@#A distance feature is presented in the temperature field measured by simulated thermometer and generated under suspension moxibustion at Zusanli (ST 36). The warm stimulation effect of sparrow-pecking moxibustion is much more obvious at the moxibustion-exerted center as compared with mild moxibustion and the area of warm stimulation generated by sparrow-pecking moxibustion is more concentrated as compared with mild moxibustion. The radiation energy produced by suspension moxibustion is scattered and attenuated in skin tissue, resulting in a certain temperature gradient in the temperature field. The warm stimulation generated at skin surface by moxibustion has a warming-dredging effect.


Subject(s)
Animals , Humans , Acupuncture Points , Moxibustion , Sparrows , Temperature , Torso
15.
Chinese Medical Journal ; (24): 1450-1456, 2021.
Article in English | WPRIM | ID: wpr-878191

ABSTRACT

BACKGROUND@#Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up.@*METHODS@#The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC).@*RESULTS@#A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001).@*CONCLUSIONS@#The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.


Subject(s)
Humans , Constriction, Pathologic , Coronary Angiography , Coronary Artery Disease/therapy , Coronary Restenosis , Follow-Up Studies , Fractional Flow Reserve, Myocardial , Pharmaceutical Preparations , Predictive Value of Tests , Retrospective Studies , Treatment Outcome
16.
Chinese Journal of Radiological Medicine and Protection ; (12): 407-412, 2021.
Article in Chinese | WPRIM | ID: wpr-910330

ABSTRACT

Objective:To investigate epithelial-mesenchymal transition and to explore the effects of mitochondrial dysfunction and increased expression of TGF-β1 pathway on epithelial-mesenchymal transition (EMT) in pancreatic adenocarcinoma after X-ray irradiation.Methods:Split-dose irradiations of total 40 Gy (2 Gy × 20 and 4 Gy × 10) of 6 MV X-rays were performed on PATU1 988 t cells. The migration of the cells were examined through transwell filter chambers. Real-time PCR was adopted to detect the expression of EMT-related factors E-cadherin, Vimentin, N-cadherin, and MMPs (MMP2 and MMP9), critical subunits of mitochondrial complex I, and TGF-β1. The expression of EMT-related factors and content of TGF-β1 was detected after carbonylcyanide-m-chlorophenylhydrazone(CCCP) treatment. Meanwhile, the migration potential of pancreatic cells was detected after small interfering RNA (siRNA) knockdown of the expression of TGF-β1.Results:After irradiation, the migration capacities of the cancer cells increased ( t=21.90, 35.64, P<0.05). The expression of N-cadherin ( t=4.42, 4.77, P<0.05), Vimentin ( t=4.57, 3.02, P<0.05), MMP2 ( t=7.27, 26.08, P<0.05), and MMP9 ( t=13.26, 7.29, P<0.05) all increased, while the expression of E-cadherin deceased ( t=8.37, 6.77, P<0.05). The expression of TGF-β1 ( t=90.49, 35.17, P<0.05) increased. The expression of TGF-β1 decreased with small interfering RNA, which paralleled the inhibition of the epithelial-mesenchymal transition and migration ( t=38.66, 11.54, P<0.05). Mitochondrial dysfunction was reflected by the decline in the membrane potential ( t=6.94, 29.71, P<0.05) and complex-related subunits. The expression of TGF-β1 ( t=47.93, P<0.05) and EMT-related factors further increased after mitochondrial function was destroyed ( t=16.51, P<0.05). Conclusions:Radiation-induced mitochondrial dysfunction can increase the expression of TGF-β1, which promotes epithelial-mesenchymal transition, and result in the migration of pancreatic cancer cell line.

17.
Braz. j. med. biol. res ; 54(7): e10236, 2021. graf
Article in English | LILACS | ID: biblio-1249317

ABSTRACT

This work aimed to research the function of MARVEL domain-containing protein 1 (MARVELD1) in glioma as well as its functioning mode. Bioinformatics analysis was utilized to assess the MARVELD1 expression in glioma tissues and its relationship with grade and prognosis, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) databases. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays were carried out to determine the impact of MARVELD1 on malignant biological behavior of glioma, such as proliferation, invasion, and migration. qRT-PCR was carried out to test the mRNA level of MARVELD1. Western blot assay was performed to measure the protein expression of MARVELD1 and JAK/STAT pathway-related proteins. MARVELD1 was expressed at high levels in glioma tissues and cell lines. Kaplan-Meier survival analysis revealed that the higher MARVELD1 expression, the shorter the survival time of patients with glioma. Also, the MARVELD1 expression in WHO IV was significantly enhanced compared to that in WHO II and WHO III. Furthermore, the functional analysis of MARVELD1 in vitro revealed that knockdown of MARVELD1 in U251 cells restrained cell proliferation, migration, and invasion, while up-regulation of MARVELD1 in U87 cells presented opposite outcomes. Finally, we found that JAK/STAT signaling pathway mediated the function of MARVELD1 in glioma. MARVELD1 contributed to promoting the malignant progression of glioma, which is the key driver of activation of JAK/STAT signaling pathway in gliomas.


Subject(s)
Humans , Animals , Rats , Brain Neoplasms , Glioma , Phenotype , Signal Transduction , Gene Expression Regulation, Neoplastic , Up-Regulation , Cell Movement , Cell Line, Tumor , Cell Proliferation , MARVEL Domain-Containing Proteins , Membrane Proteins , Mice, Nude , Microtubule-Associated Proteins
18.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 13-19, 2020.
Article in Chinese | WPRIM | ID: wpr-873212

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19), the health authorities in various regions have formulated a group of traditional Chinese medicine (TCM) diagnosis and treatment programs based on the consensus analysis of etiology and pathogenesis of TCM experts, and recommended the guiding prescriptions for different syndromes in three stages of prevention, treatment and recovery. In order to effectively summarize the understanding of the pathogenesis of each scheme and the rules of the formulation of various prescriptions, based on 49 TCM prevention and treatment plans issued by the health administration departments, 308 TCM prescriptions were sorted by stages (151 prescriptions in the treatment period, 118 prescriptions in the prevention period and 39 prescriptions in the recovery period). The 2019-nCoV pneumonia prescriptions was further processed by using TCM inheritance platform system. The common syndromes and the frequency of commonly used Chinese medicines were summed up. The commonly used drug pairs and combinations in different stages were extracted, and their association rules were analyzed. The rules of the Chinese herbal prescription for COVID-19 were preliminarily summarized. During the treatment period, the main syndrome types are inner blocking causing collapse, epidemic toxin in the lung, cold dampness in the lung and toxic heat in the lung, involving 187 kinds of herbs, 29 kinds of herbs with single taste frequency more than 20 times.Armeniacae Semen Amarum is the most frequently used, Gypsum Fibrosum-Armeniacae Semen Amarum is the most frequently used drug-pair, the core formula is Maxing Shigan Tang, and the main pathogenesis is cold, wet and heat. There is no unified syndrome type in the prevention period, involving 119 herbs in total. There are 13 kinds of herbs with single taste frequency more than 20 times. The most frequently used is Astragali Radix. The most frequently used medicine pair is Astragali Radix-Saposhnikoviae Radix. The core formula is Yupingfeng San, and the main pathogenesis is Qi deficiency. During the recovery period, the main syndromes are deficiency of lung and spleen Qi deficiency and Qi and Yin deficiency, involving 113 herbs, 12 kinds of herbs with single taste frequency more than 10 times, Poria with the highest frequency of use, Citri Reticulatae Pericarpium-Poria with the highest frequency of drug pairing, Erchentang and Shengmaiyin with the main pathogenesis of deficiency of spleen Qi and Yin. The purpose of this study is to provide multiple references for strengthening clinical precise treatment, improving the effect of TCM treatment and promoting the management of TCM prevention and control resources.

19.
Acta Anatomica Sinica ; (6): 442-445, 2020.
Article in Chinese | WPRIM | ID: wpr-1015560

ABSTRACT

Objective To analyze the changes of serum biochemical indexes with age and gender in Xinjiang Uygur and Kazak populations, and to compare the differences of serum biochemical indexes between Xinjiang Uygur and Kazak populations in gender and age. Methods Totally 511 Xinjiang Uygur and Kazak healthy adults were randomly selected from a hospital in Xinjiang Uygur autonomous region for normal physical examination, including 252 and 259 Xinjiang Uygur and Kazak healthy adults. Serum biochemical indexes were detected by CX-7 automatic biochemical analyzer produced by Beckman, USA, and statistical analysis was conducted by variance analysis, t test, correlation analysis and chi-square test. Results Xinjiang Uygur nationality and Kazak serum biochemical indexes for the male and the female, including glutamic-pyruvic transaminase (GPT), direct bilirubin (DBil), uric acid (UA), creatinine (Cre) and urea (Ure), glucose (Glu), total bilirubin(TBil), cystatin C(Cys-C) increased with the growth of the age, and sex between different age groups were statistically significant (P 0. 05). There were statistically significant differences in Glu, TG, TC, LDL and HDL between Xinjiang Uygur and Kazak people of the same gender and age group (P < 0. 05). Conclusion The serum biochemical indexes of Uygur and Kazak in Xinjiang are different in different ages and genders. The Glu and lipid levels of Uygur nationality in Xinjiang are different from those of Kazak nationality.

20.
Journal of Integrative Medicine ; (12): 222-228, 2020.
Article in English | WPRIM | ID: wpr-829110

ABSTRACT

OBJECTIVE@#To examine the association between traditional Chinese medicine (TCM), preconception health patterns and fertility outcomes.@*METHODS@#A community-based prospective cohort study was conducted in China. A total of 3012 newly married women who were willing to conceive within 2 years were enrolled in the study and took National Free Prepregnancy Checkups (NFPC). A reliably structured self-rating scale was used to measure the TCM preconception health patterns of the enrolled women. A 3-year follow-up was conducted to obtain the fertility outcomes, including pregnancy rate, time to pregnancy, spontaneous miscarriage and newborn status. Statistical analyses were conducted using Chi-square or Fisher's exact tests, logistic regression models, general linear models and the Cox proportional hazard model.@*RESULTS@#The fertility outcomes showed no statistic correlations to the terms of NFPC in this population. Approximately a half of the women (46.66%) had unhealthy patterns. Women with qi & blood-deficiency (odds ratio [OR] = 35.19, 95% confidence interval [CI] = 1.55-801.15) or qi-stagnation (OR = 4.55, 95% CI = 0.90-23.06) pattern took a longer time to get pregnant, and those with qi-stagnation (OR = 2.05, 95% CI = 1.1-3.82) or yang-deficiency (OR = 1.91, 95% CI = 1.12-3.25) pattern had a higher risk of spontaneous miscarriage.@*CONCLUSION@#Three unhealthy TCM patterns during the preconception period might be risk factors for low fecundity or poor pregnancy outcomes. The TCM preconception pattern identification may provide a convenient and effective way to screen for potential pregnancy risks beyond the NFPC. Further, appropriate interventions based on the TCM preconception health patterns are needed to improve quality in women's fecundability and birth outcomes.

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