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1.
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.

2.
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
3.
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.

4.
Article in Chinese | WPRIM | ID: wpr-856365

ABSTRACT

Objective: To evaluate the risk factors for postoperative indwelling catheter following enhanced recovery after primary unilateral total knee arthroplasty (TKA) under general anesthesia. Methods: Patients who underwent primary unilateral TKA under general anesthesia between January 2017 and August 2018 were enrolled in the study. Among them, 205 patients who met the selection criteria were included in the study, and the clinical data were collected, including gender, age, body mass index, preoperative range of motion, Hospital for Special Surgery (HSS) score, American Society of Anesthesiologists (ASA) score, disease type, comorbidity, hemoglobin, hematocrit, blood volume, length of operation and operation time, whether to keep drainage after surgery, intraoperative blood loss, total blood loss, and preoperative, intraoperative, postoperative fluid infusions, and total fluid infusion on the day of surgery, urine volume on the day of surgery. Univariate analysis and logistic regression analysis were used to screen the risk factors for postoperative indwelling catheter. Length of stay and incidences of complications (intermuscular vein thrombosis, deep vein thrombosis, pulmonary embolism, incision swelling and exudation, electrolyte disorder, nausea and vomiting, and urinary tract infection) were compared between the patients with or without indwelling catheter. Results: Indwelling catheter occurred in 41 (20%) of 205 patients. Single factor analysis showed that the influence factors were age, gender, keeping drainage after surgery, total fluid infusion and urine volume on the day of surgery ( P<0.05). The multiple factors analysis showed that the males and more urine volume on the day of surgery were the significant risk factors for indwelling catheter after primary TKA ( P<0.05). In addition, postoperative length of stay was shorter and the incidence of urinary tract infection was lower in non-indwelling catheter group than in indwelling catheter group, showing significant differences ( P<0.05). Conclusion: The male patients with more urine on the day of surgery have higher risk for indwelling catheter after primary unilateral TKA under general anesthesia with an enhanced recovery program.

5.
Chinese Medical Journal ; (24): 2703-2711, 2020.
Article in English | WPRIM | ID: wpr-877829

ABSTRACT

With the changing lifestyle and the acceleration of aging in the Chinese population, the incidence and mortality of colorectal cancer (CRC) have risen in the last decades. On the contrary, the incidence and mortality of CRC have continued to decline in the USA since the 1980s, which is mainly attributed to early screening and standardized diagnosis and treatment. Rectal cancer accounts for the largest proportion of CRC in China, and its treatment regimens are complex. At present, surgical treatment is still the most important treatment for rectal cancer. Since the first Chinese guideline for diagnosis and treatment of CRC was issued in 2010, the fourth version has been revised in 2020. These guidelines have greatly promoted the standardization and internationalization of CRC diagnosis and treatment in China. And with the development of comprehensive treatment methods such as neoadjuvant chemoradiotherapy, targeted therapy, and immunotherapy, the post-operative quality of life and prognosis of patients with rectal cancer have improved. We believe that the inflection point of the rising incidence and mortality of rectal cancer will appear in the near future in China. This article reviewed the current status and research progress on surgical therapy of rectal cancer in China.


Subject(s)
China/epidemiology , Colonic Neoplasms , Colorectal Neoplasms , Humans , Quality of Life , Rectal Neoplasms/surgery
6.
Gut and Liver ; : 727-734, 2020.
Article in English | WPRIM | ID: wpr-833176

ABSTRACT

Background/Aims@#Esophagogastric junction adenocarci-noma (EJA) is a malignant tumor associated with high mor-bidity and has attracted increasing attention due to a rising incidence and low survival rate. Pathological biopsy is the gold standard for diagnosis, but noninvasive and effective tests are lacking, resulting in diagnoses at advanced stages.This study explored the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in EJA. @*Methods@#A total of 120 EJA patients and 88 normal controls were recruited, and their serum levels of IGFBP7 were measured by enzymelinked immunosorbent assay. Receiver operating character-istic (ROC) curve analysis was used to assess the diagnostic value, and Pearson chi-square analysis was used to evaluate the correlation between IGFBP7 and clinical parameters. Ka-plan-Meier survival analysis was carried out to assess the ef-fect of IGFBP7 on overall survival (OS). @*Results@#The levels of IGFBP7 were higher in both early- and late-stage EJA patients than in normal controls (p<0.001). The area under the ROC curve for EJA patients was 0.794 (95% confidence interval [CI], 0.733 to 0.854), with a cutoff value of 2.716 ng/mL, a sensitivity of 63.3% (95% CI, 54.0% to 71.8%) and a specific-ity of 90.9% (95% CI, 82.4% to 95.7%). For the diagnosis of early-stage EJA, the same cutoff value and specificity were obtained, but the sensitivity of IGFBP7 was 54.3% (95% CI, 36.9% to 70.8%). Patients with low IGFBP7 protein expres-sion had lower OS than those with high expression (p=0.034).The multivariate analysis showed that IGFBP7 is an inde-pendent prognostic factor for EJA (p=0.011). @*Conclusions@#Serum IGFBP7 acts as a potential diagnostic and prognostic marker for EJA.

7.
Acta Anatomica Sinica ; (6): 103-108, 2020.
Article in Chinese | WPRIM | ID: wpr-844559

ABSTRACT

Objective To observe the effect of the peptide compound urantide on the expression of type I collagen (Col I ) in the heart tissue of rats with atherosclerosis ( As) , and to explore its mechanism of prevention and treatment of heart damage in As rats. Methods Sixty healthy male 3-week-old SPF Wistar rats were selected. The As model was established by intraperitoneal injection of vitamin D3(VD3) to damage the arterial intima and high-fat diet. They were randomly divided into normal group, As model group, simvastatin group and urantide (3 days, 7 days, 14 days) groups. HE staining and Masson trichrome staining were used to observe the morphology and collagen fiber expression of rat hearts. Immunohistochemistry, Western blotting and Real-time PCR were used to detect the expression of Col I protein and gene in rat heart. Results Compared with the normal group, pathological phenomena such As myocardial cell degeneration, intercellular infiltration of a large number of neutrophils, scattered foam cells and hyperemia and hemorrhage were observed in the heart tissues of the As model group. Meanwhile, collagen fibers increased, and the gene and protein expression levels of Col I increased. Compared with the As model group, the cardiac pathological phenomena were effectively alleviated after the treatment with urantide. With the extension of the administration time, the collagen fibers decreased, and the gene and protein expression levels of Col I were gradually down-regulated, especially the effect was the best when the drug was given for 14 days. Conclusion Urantide can inhibit the expression of Col I in As heart to reduce myocardial interstitial damage, and has a protective effect on the heart of As rats.

8.
Acta Pharmaceutica Sinica ; (12): 2606-2617, 2020.
Article in Chinese | WPRIM | ID: wpr-837513

ABSTRACT

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein system exerts genome editing effect through cleaving DNA double strands using RNA-guided endonuclease. Double-strand breaks were repaired via homology directed repair (HDR) or nonhomologous end joining (NHEJ), accompanied by insertions, deletions or replacements into the genome. As a powerful tool, CRISPR/Cas system has provided tremendous convenience for basic researches and may pave the path to treat genetic diseases and cancers. Genome editing could be achieved only when both CRISPR RNA and Cas protein are delivered into nucleus of target cell. Compared with physical and viral delivery, nonviral delivery of CRISPR/Cas system possesses unique advantages in terms of safety, loading capacity and preparation. Hence, many researchers have devoted themselves to the development of nonviral vectors with high delivery efficiency which is important for the application and translation of the promising technology. Advances on cationic liposomes, lipid like nanoparticles, cationic polymers, AuNPs, vesicles, polypeptides, proteins and so on have been made. We will give a brief introduction to the mechanism of CRISPR/Cas9, problems faced by nonviral delivery of CRISPR/Cas9 system in forms of plasmid, mRNA and protein; examples of non-viral vectors, hoping to give some hints on design of safe and efficient nonviral vectors for genome editing.

9.
Article in Chinese | WPRIM | ID: wpr-828083

ABSTRACT

Jiaotai Pills is a traditional medical prescription to treat the incompatibility of heart and kidney. It has the distinctive functions of heart and kidney communication, sedation and hypnosis, anti-anxiety and depression, as well as the improvement of insulin resistance. However, this pill is broadly used to cure insomnia, anxiety, depression, and diabetes in the contemporary clinical trials. Based on the article, it illustrates the research progress of the chemical ingredients, pharmacological actions, and clinical applications of Jiaotai Pills. With respect to the "five principles" of Q-marker in Chinese medicine, the Q-marker of Jiaotai Pills is comprehensively predicted and analyzed, noting that berberine, epiberberine, coptisine chloride, palmatine chloride, berberine chloride, berberrubine chloride, ferulic acid, cinnamic acid, cinnamaldehyde, proanthocyanidin B2 can be treated as the Q-marker of Jiaotai Pills. In addition, these components of Q-marker have been selected as indicators to provide a significant reference for the quality control and surveillance research of Jiaotai Pills.


Subject(s)
Biomarkers , Drugs, Chinese Herbal , Quality Control
10.
Article in Chinese | WPRIM | ID: wpr-774105

ABSTRACT

OBJECTIVE@#To study the distribution of peripheral blood lymphocyte subsets in healthy children aged 0-6 years.@*METHODS@#A total of 826 healthy Han children aged 0-6 years were recruited. According to their age, the children were divided into four groups: newborn, infant, toddler and preschool. Their peripheral blood samples were collected to measure the percentages of lymphocyte subsets by flow cytometry.@*RESULTS@#There were significant differences in the percentages of CD3 T cells, CD3CD4 T cells and CD3CD19 B cells and the CD4/CD8 ratio between boys and girls (P<0.05). The girls had a lower percentage of CD3CD19 B cells, higher percentages of CD3 T cells and CD3CD4 T cells and a higher CD4/CD8 ratio than the boys. The newborn group had the highest percentages of CD3 T cells and CD3CD4 T cells and the highest CD4/CD8 ratio (P<0.05). The percentage of CD3CD4 T cells and the CD4/CD8 ratio gradually decreased with age and the preschool group had the lowest values (P<0.05). The newborn group had the lowest percentages of CD3CD19 B cells and CD3CD16CD56 NK cells (P<0.05). The percentage of CD3CD16CD56 NK cells gradually increased with age and the preschool group had the highest percentage (P<0.05). The percentage of CD3CD19 B cells reached the peak in the toddler period and then decreased with age (P<0.05). The preschool group had the highest percentage of CD3CD8 T cells (P<0.05). The variation trend of distribution of lymphocyte subsets in boys from different age groups was consistent with that in children from different age groups. For girls, the newborn group had the highest percentage of CD3CD4 T cells and CD4/CD8 ratio (P<0.05).@*CONCLUSIONS@#The distribution of peripheral blood lymphocyte subsets in healthy children is significantly different across ages and sexes. Therefore, the reference values should be established according to age and sex.


Subject(s)
Antigens, CD19 , B-Lymphocytes , Child , Child, Preschool , Female , Flow Cytometry , Humans , Infant , Infant, Newborn , Killer Cells, Natural , Lymphocyte Count , Lymphocyte Subsets , Male
11.
Article in Chinese | WPRIM | ID: wpr-773253

ABSTRACT

In this paper,the effects of active fractions of Ferula ferulaeoides on the growth and apoptosis of human gastric cancer cell MGC-803 transplantation tumor were systematically studied. The subcutaneous ectopic transplantation tumor model was established in human gastric cancer MGC-803 nude mice by cell suspension implantation method. The anti-tumor rate and organ index were used to evaluate the anti-tumor effect of the active fractions of F. ferulaeoides on the tumor-bearing nude mice. HE staining,TUNEL staining,RT-PCR,Western-blot and ELISA were used for pathological examination,apoptosis observation,and detection of apoptosis-related genes,proteins and cytokines expression. The results showed that as compared with the model group,the low,medium and high doses of the active fraction of F. ferulaeoides had inhibitory effects on xenografts in nude mice,respectively,in a dose-dependent manner; the apoptotic ratio was increased with the increase of drug concentration. As compared with the model group,F. ferulaeoides could down-regulate the expression of survivin mRNA in nude mice,and the protein expression levels of Bax,Bcl-2,caspase-3 and caspase-9 in tumor tissues of nude mice could be increased to different degrees in F. ferulaeoides groups. The contents of IL-10 and TGF-β1 in plasma of nude mice were decreased in high dose group of F. ferulaeoides active fractions. The results indicated that F. ferulaeoides can significantly inhibit the growth of human gastric cancer MGC-803 subcutaneously transplanted tumor,and its mechanism may be related with down-regulating the expression of survivin mRNA,and up-regulating the expression of apoptosis-related proteins Bax,caspase-3 and caspase-9.


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cell Line, Tumor , Cytokines , Metabolism , Ferula , Chemistry , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Plant Extracts , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Stomach Neoplasms , Drug Therapy , bcl-2-Associated X Protein , Metabolism
12.
Chinese Journal of Biotechnology ; (12): 281-289, 2019.
Article in Chinese | WPRIM | ID: wpr-771378

ABSTRACT

In previous studies, we found that truncated rotavirus VP4* (aa 26-476) could be expressed in soluble form in Escherichia coli and confer high protection against rotavirus in the mouse mode. In this study, we further improved the immunogenicity of VP4* by polymerization. The purified VP4* was polymerized through incubation at 37 ℃ for 24 h, and then the homogeneity of the particles was analyzed by HPLC, TEM and AUC, while the thermal stability and antigenicity was analyzed by DSC and ELISA, respectively. Finally, the immunogenicity and protective efficacy of the polymers analyzed by a mouse maternal antibody model. The results showed that VP4* aggregated into homogeneous polymers, with high thermostability and neutralizing antibody binding activity. In addition, VP4* polymers (endotoxin <20 EU/dose) stimulated higher neutralizing antibodies and confer higher protection against rotavirus-induced diarrhoea compared with the VP4* trimers when immunized with aluminium adjuvant. In summary, the study in VP4* polymers provides a new strategy for the development of recombinant rotavirus vaccines.


Subject(s)
Animals , Antibodies, Viral , Antigens, Viral , Capsid , Capsid Proteins , Mice , Polymerization , Rotavirus , Rotavirus Infections
13.
Article in Chinese | WPRIM | ID: wpr-775886

ABSTRACT

The sensitization phenomena and regularities of Hegu (LI 4) were preliminarily explored. The relevant literature regarding Hegu (LI 4) sensitization were collected by computer retrieval at Cochrane Library, Pubmed, Embase (OvidSP), China Journal Full Text Database (CNKI), China Biomedical Literature Database (CBM), VIP and Wanfang (WF) databases as well as manual searching, and a modern literature database of Hegu (LI 4) sensitization was established. The information of disease type, sensitization type, detection method and index were collected. Frequency statistics method was used for analysis. As a result, 47 literatures were included, of which heat sensitivity was the most common type of sensitization, and diseases of liver and gallbladder, limb meridians, lung system, and spleen-stomach system were the most common types of diseases. The detection method of sensitization was various, among them, potassium ion introduction method and hot-water tail-flick method were mainly used for pain sensitivity, while acupoint resistance measuring instrument was mainly used for electric sensitivity, while thermal infrared imager was mainly used for heat sensitivity, while infrared spectrometric analyzer was mainly used for light sensitivity, while pressing pain measuring instrument was used for pressing sensitivity. Detection index was different, pain sensitivity detected pain threshold, electric sensitivity mainly detected acupoint resistance, heat sensitivity mainly detected temperature, light sensitivity detected average sharpness and average energy of infrared radiation, pressing sensitivity detected pressing-pain threshold. In conclusion, the regularities of sensitization of Hegu (LI 4) were preliminarily summarized, which involved five sensitization types: heat sensitivity, electric sensitivity, pain sensitivity, pressing sensitivity and light sensitivity. The sensitization of Hegu (LI 4) was commonly seen in facial paralysis, bronchial asthma, allergic rhinitis, tinnitus, ulcerative colitis. The temperature, pain threshold, pressing-pain threshold, average sharpness and average energy of infrared radiation of Hegu (LI 4) in pathological condition were lower than those in healthy subjects, and the resistance value was higher than that of healthy subjects.


Subject(s)
Acupuncture Points , Bibliometrics , China , Facial Paralysis , Humans , Meridians
14.
Article in Chinese | WPRIM | ID: wpr-802320

ABSTRACT

Objective:To prepare standard decoction of Saposhnikoviae Radix pieces,and conduct a study on the quality standards, in order to provide the scientific reference for the study of clinical application and other decoction standard decoctions. Method:By the traditional water decocting method,11 batches of standard decoction of Saposhnikoviae Radix pieces were prepared to determine pH,prim-O-glucosylcimifugin and 4'-O-β-D-glucosyl-5-O-methylvisamminol content,calculate the paste rate and transfer rate,and investigate the feasibility of the measurement method. An analytical method for HPLC fingerprint was established. Hypersil ODS2 column (4.6 mm×250 mm,5 μm) was adopted and eluted with methanol-water as the mobile phase in a gradient mode. The detection wavelength was 254 nm,the flow rate was 1 mL·min-1,and the column temperature was 25℃. The fingerprint analysis method was used to evaluate the similarity of the 11 batches of standard decoction of Saposhnikoviae Radix pieces. Result:Through the determination of 11 batches of standard decoctions of Saposhnikoviae Radix pieces,the average pH value was 5.5,the paste-out rates were between 34.3% and 46.3%,and the average paste-out rate was 41.4%,the standard deviation was 3.7%, the transfer rate of prim-O-glucosylcimifugin was 66.8%-93.5%,the average metastasis rate was 79.4%,the standard deviation was 12.1%, the transfer rate of 4'-O-β-D-glucosyl-5-O-methylvisamminol was 70.4%-98.2%,the average transfer rate was 83.40%,the standard deviation of 10.8%. The results of various methodological studies were consistent with the requirements of RSD. The fingerprinting analysis was performed using similarity evaluation software for traditional Chinese medicine fingerprints,and 9 principal common peaks were identified. The similarity was higher than 0.9. Conclusion:The quality evaluation method established in this study has a good stability,precision and repeatability. The fingerprints have a high similarity,which is suitable for the quality evaluation of standard decoctions of Saposhnikoviae Radix pieces, and can provide the scientific basis for the quality evaluation of other related preparations.

15.
Article in Chinese | WPRIM | ID: wpr-802026

ABSTRACT

Objective:To observe the expression of mammalian target of rapamycin (mTOR) that mediates autophagy in pulmonary fibrosis and the effect of autophagy in the formation of pulmonary fibrosis, in order to explore the treatment mechanism of Buyang Huanwu Tang on pulmonary fibrosis. Method:Totally 144 C57BL/6 mice were randomly divided into 6 groups:sham operation group, model group, prednisone group, high-dose Buyang Huanwu Tang group, medium-dose Buyang Huanwu Tang group and low-dose Buyang Huanwu Tang group, with 24 mice in each group. The sham operation group was injected with the same amount of 0.9% saline. The remaining groups were treated with bleomycin tracheal injection to replicate the pulmonary fibrosis model. After modeling, sham operation group and model group were given 0.9% normal saline (0.01 g·kg-1·d-1), group high-dose Buyang Huanwu Tang group was given Buyang Huanwu Tang (28.08 g·kg-1·d-1), medium-dose Buyang Huanwu Tang group was given Buyang Huanwu Tang (14.04 g·kg-1·d-1), low-dose Buyang Huanwu Tang group was given Buyang Huanwu Tang(7.02 g·kg-1·d-1), and P group was given prednisone (0.455 g·kg-1·d-1) by gavage. The samples were taken in batches on the 7th, 14th and 28th days after modeling; degrees of alveolitis and fibrosis in mice were observed by hematoxylin-eosin (HE) staining and Masson staining. The mTOR protein, ribosomal S6 protein and microtubule associate protein 1 hight chain3-Ⅱ(MAP1LC3-Ⅱ) of mouse lung tissue were detected by Western blot; electron microscopy was used to observe the autophagy of lung tissue in mice. Result:Compared with the sham-operated group, the degrees of alveolitis and pulmonary fibrosis were significantly severer in the model group on 7th, 14th and 28th days (PPPPConclusion:The mTOR protein is activated in mice lung tissue, autophagy is inhibited, mTOR protein participates in the pathogenesis of pulmonary fibrosis by inhibiting autophagy; Buyang Huanwu Tang has a certain therapeutic effect on BLM-induced pulmonary fibrosis in mice, and its mechanism may be related to the down-regulation of mTOR protein expression that mediates autophagy.

16.
Article in Chinese | WPRIM | ID: wpr-851405

ABSTRACT

Objective The inclusion complex of vincamine (VIN) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared and characterized. Molecular simulation method was used to study the formation mechanism of inclusion complex. Methods The inclusion complex of VIN/HP-β-CD was prepared by saturated solution. The preparation technology of VIN/HP-β-CD inclusion complex was optimized by orthogonal design, and taking the drug-loading of the inclusion compound as the index. The stability constant of inclusion complex between VIN and HP-β-CD was studied by UV-Vis spectrometry titration, and the inclusion ratio was determined by Job plots method. The VIN/HP-β-CD inclusion complex was characterized by scanning electron microscope (SEM), X-ray powder diffractometry (XRD), infrared spectroscopy (IR), thermal analysis techniques (TG and DSC), and nuclear magnetic resonance (1H, 2D NMR). The water solubility of the VIN/HP-β-CD inclusion complex was measured and the stability test was conducted in the simulated human gastric juice and intestinal fluid environment. Molecular docking and molecular dynamics were used to study the forming mechanism of supramolecular system of VIN/HP-β-CD. Results Using saturated solution method, the optimum conditions of inclusion were: 1:1 for molar ratio of VIN and HP-β-CD, 40 ℃ for inclusion temperature, 7 h for inclusion time and volume ratio of methanol to water (1:6) as solvent; Job curve and UV-vis spectroscopy showed that inclusion ratio of host-guest inclusion complexes was 1:1; After VIN formed inclusion complexes with HP-β-CD, its solubility increased from 0.04 mg/mL to 16.5 mg/mL, and the thermal decomposition temperature of VIN increased from 240.5 ℃ to 306.1 ℃. 1H-NMR and NOESY spectra indicated that the inclusion complex was formed by the a-ring of VIN entering from the large end of HP-β-CD. Quantum chemical calculation and molecular docking indicated that the optimal inclusion mode was consistent with the results of NMR studies. Molecular dynamics studies showed that VIN can penetrate into the hydrophobic cavity of HP-β-CD in water environment, and the interaction between host and guest was strengthened. The space size of host-guest matched better. Conclusion The solubility and thermal stability were significantly improved after the formation of inclusion complex with VIN and HP-β-CD. Hydrophobicity, hydrogen bonding, and van der Waals forces were the main driving forces for inclusion complex formation.

17.
Article in Chinese | WPRIM | ID: wpr-797017

ABSTRACT

Objective@#To evaluate the cost-effectiveness of seasonal influenza vaccination, compared to no vaccination, for the elderly aged ≥60 years old in China.@*Methods@#A static life-time Markov model is conducted to simulate the Chinese elderly population aged ≥60 years old. Taking the health care system perspective, one-year analytic cycle length is used for each influenza season. The model was assumed to be repeated until the individual reaches 100 years old. Three interventions were evaluated, including no vaccination, annual trivalent influenza vaccination, and annual quadrivalent influenza vaccination. Using the threshold of 3 times GDP per capita per Quality-adjusted life year (QALY) (193 932/QALY), the incremental cost-effectiveness ratio (ICER) was calculated to compare the cost-effectiveness of every two interventions.Model inputs like data for costs and utilities were from studies on Chinese population if they were available. QALY was used to measure health utility. One-way sensitivity analysis and probabilistic sensitivity analysis were adopted to quantify the level of confidence of the model output.@*Results@#The total influenza associated costs of no vaccination would be 603 CNY per person, while the total costs of annual trivalent vaccination would be 1 027 CNY. Using trivalent vaccine would result in 0.007 QALY gained per person compared to no vaccination, with an increased cost of 424 CNY per person. The ICER of trivalent vaccination over no vaccination for all the elderly population in China would be 64 026 CNY per QALY gained, which was less than the threshold of 3 times GDP per capita. The total costs of annual quadrivalent vaccination would be 1 988 CNY. Using quadrivalent vaccine would result in 0.008 additional QALY gained per person compared to no vaccination, with an increased cost of 1 385 CNY per person. The ICER of quadrivalent vaccination over no vaccination would be 174 081 CNY per QALY gained, which was less than the threshold of 3 times GDP per capita.@*Conclusion@#Vaccinating elderly population would improve health utilities at higher health care costs for the elderly. Using the threshold of 3 times GDP per capita per QALY (193 932/QALY), both trivalent and quadrivalent vaccination would be cost-effective compared to no vaccination in elderly Chinese population.

18.
Article in English | WPRIM | ID: wpr-773635

ABSTRACT

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.


Subject(s)
Analgesics , Chemistry , Animals , Chronic Pain , Drug Therapy , Abietanes , Chemistry , Drug Evaluation, Preclinical , Enzyme Inhibitors , Chemistry , Female , Humans , Male , Mice , Mice, Inbred ICR , Monoacylglycerol Lipases , Metabolism , Structure-Activity Relationship
19.
Article in Chinese | WPRIM | ID: wpr-690777

ABSTRACT

<p><b>OBJECTIVE</b>To explore the acupoint electrosensitivity and regularity for assisting the clinical diagnosis and treatment so as to improve the clinical therapeutic effects.</p><p><b>METHODS</b>By means of the computer retrieval (CBMdisc, CNKI, VIP, WanFang, PubMed and EMBASE) and manual retrieval, the relevant literature on acupoint electrosensitivity was reviewed and the modern literature database of acupoint electrosensitivity was established. Using bibliometric, the relations were analyzed among the detected indexes, acupoints, meridians and disorders in the conditions of acupoint electrosensitivity, and the potential regularity was explored.</p><p><b>RESULTS</b>The general detection indexes of acupoint electrosensitivity were resistance, inertia area, volt-ampere area, electric conduction quantity, electric potential, electric current and capacitance. The electrosensitive points included meridian points, auricular points and extraordinary points. Among those points, the electrosensitivity easily occurred at the special points.</p><p><b>CONCLUSION</b>The acupoint electrosensitivity is mainly reflected on the electrical impedance and volt-ampere characteristics. The relative specificity exists between acupoint electrosensitivity and disorders. In clinical practice, detecting acupoint electrosensitivity may assist the diagnosis and instruct acupoint selection to improve the clinical therapeutic effects.</p>

20.
Article in English | WPRIM | ID: wpr-690603

ABSTRACT

<p><b>OBJECTIVE</b>To compare the eye-movement patterns of Chinese children with developmental dyslexia (DD children) with those of non-dyslexic children as they perform the Stroop Color and Word Test (SCWT), and to explore the relationship between their eye-movement patterns and interference effect.</p><p><b>METHODS</b>An EyeLink II was used to record the eye-movement parameters of 32 DD children and 37 non-dyslexic children as they performed the SCWT. The independent samples t-test and repeated measures were used to analyze behavioral and eye-movement parameters.</p><p><b>RESULTS</b>Compared to the control group, Chinese DD children presented lower accuracy (F = 8.488), slower response time (F = 25.306), and larger interference effect (t = 2.29); Chinese DD children also exhibited lower frequency of fixations (F = 6.069), greater numbers of saccades (F = 7.914) and fixations (F = 5.272), and shorter mean saccade distance (F = 4.03). All behavioral and eye-movement parameters differed significantly among the three tasks in the SCWT. There was significant interaction between groups and tasks in accuracy (F = 5.844), and marginally significant interaction in response time (F = 3.040). Chinese DD children tended to have lower accuracy and longer response time than the control group in the 'color-word naming' task.</p><p><b>CONCLUSION</b>Compared to non-dyslexic children, Chinese DD children are subject to a stronger interference effect. When performing the SCWT, Chinese DD children exhibit abnormal eye-movement patterns, namely shorter mean saccade distance, lower frequency of fixations, and more fixations and saccades. These abnormal eye movements may be relatively stable oculomotor patterns of DD children performing visual processing, and not influenced by impaired interference effect.</p>

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